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Lupus Clinical Trials

New Medical Therapies™

Hepatitis C; Chronic

April 28, 2014

Merck issued results of an ongoing, multiarm, phase II trial combining MK-5172 and MK-8742 for the treatment of chronic HCV Genotype 1 infection (GT1). The two-part, parallel-group, randomized (within group) trial evaluated different treatment durations of MK- 5172 (100mg once daily) plus MK-8742 (50mg once daily), with or without RBV. In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen, a sustained viral response (SVR) was observed in 98% (42/43) of patients administered MK-5172/MK-8742 alone and 94% (75/80) in those administered MK-5172/MK-8742 plus RBV. The most common adverse events recorded in the RBV and RBV-free treatment groups, respectively, were fatigue (32%, 23%), headache (20%, 33%), nausea (21%, 16%), diarrhea (13%, 9%) and insomnia (13%, 7%). There were no early discontinuations due to drug-related adverse events and no clinically significant abnormalities detected in routine laboratory analysis of hematologic markers.

April 21, 2014

Gilead Sciences reported results of a phase II studies of sofosbuvir (SOF) for the treatment of chronic hepatitis C virus (HCV) infection. The ongoing, open-label trial evaluated SOF 400mg and the NS5A inhibitor ledipasvir (LDV) 90mg, with and without ribavirin (RBV) twice-daily (1,000mg/day or 1,200mg/day), among HCV-infected patient populations. 100% (n=26/26) of treatmentnaïve genotype 3 patients receiving 12 weeks of LDV/SOF plus RBV and 64% (n=16/25) of treatment-naïve genotype 3 patients receiving 12 weeks of LDV/SOF without RBV achieved a sustained virologic response 12 weeks after completing therapy (SVR12). Among genotype 1-infected patients who had failed prior treatment with SOF plus RBV, 100% (19/19) achieved SVR12 following 12 weeks of LDV/SOF plus RBV. Additionally, 65% (n=13/20) of genotype 1-infected patients with decompensated or Child-Turcotte-Pugh Class B cirrhosis receiving 12 weeks of LDV/SOF without RBV achieved SVR12. The EMA accepted a request for accelerated assessment for LDV/SOF.

March 17, 2014

Boehringer Ingelheim issued results of a phase III trial of faldaprevir for the treatment of 308 hepatitis C (HCV) treatment-naïve or experienced patients with HCV/HIV co-infection. Patients were enrolled in either 120mg or 240mg faldaprevir dose groups. Further, 80% of all patients were eligible for randomization to a shortened duration of treatment (24 v. 48 weeks) because they achieved protocol-defined early treatment success (ETS). In each faldaprevir dose group, 71% (120mg) and 72% (240mg) of patients achieved Hepatitis C viral cure 12 weeks after the conclusion of treatment (SVR12). SVR12 results were consistent across patients regardless of HCV genotype-1 subtype (GT1a or GT1b), presence of compensated cirrhosis, dose and duration of faldaprevir and duration of faldaprevir in combination with pegylated interferon and ribavirin (PegIFN/RBV). In a post hoc analysis, 75% of patients with the Q80K variant achieved SVR12 compared with 71% of patients who did not have the variant. Serious adverse events (AEs) were reported in 32 patients (10%). To date, 24 patients have prematurely discontinued faldaprevir due to AEs. The most frequent AEs were nausea (37%), fatigue (34%), diarrhea (27%), headache (25%) and weakness (23%). The NDA for faldaprevir has been accepted for filing by the FDA.

February 10, 2014

AbbVie issued results of four phase III trials of a fixed-dose combination of ABT-450/ ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice daily, for the treatment of chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. PEARL-II is a global, multi-center, randomized, openlabel, controlled study enrolling 179 GT1b treatment-experienced patients with no evidence of liver cirrhosis: 91 patients randomized to the regimen without ribavirin for 12 weeks and 88 patients randomized to the regimen with ribavirin for 12 weeks. In the ribavirin-free arm, 100% (n=91/91) of patients achieved SVR12, while 97% (n=85/88) achieved SVR12 in the ribavirin-containing arm. There were no patients who experienced virologic relapse or breakthrough. PEARL-III is a global, multi-center, randomized, double-blind, placebo-controlled study enrolling 419 GT1b treatment-naive patients with no evidence of liver cirrhosis: 209 patients randomized to the regimen without ribavirin for 12 weeks and 210 patients randomized to the regimen with ribavirin for 12 weeks. 99% receiving the regimen without ribavirin (n=207/209) and 99% receiving the regimen with ribavirin (n=209/210) achieved SVR12. PEARL-IV is a global, multi-center, randomized, double-blind, placebo-controlled trial enrolling 305 GT1a treatment-naive patients with no evidence of liver cirrhosis: 205 patients randomized to the regimen without ribavirin for 12 weeks and 100 patients randomized to the regimen with ribavirin for 12 weeks. 90% of patients receiving the regimen without ribavirin (n=185/205) and 97% receiving the regimen with ribavirin (n=97/100) achieved SVR12.Virologic relapse or breakthrough was noted in 8% of patients without ribavirin and 2% of patients receiving ribavirin. TURQUOISE-II was completed exclusively in GT1 cirrhotic patients investigating an alloral, interferon-free regimen. It is a global, multi-center, randomized, open-label study enrolling 380 GT1a and GT1b, treatmentnaive and treatment-experienced patients with compensated cirrhosis: 208 patients randomized to the regimen with ribavirin for 12 weeks and 172 patients randomized to the regimen with ribavirin for 24 weeks. Following 12 weeks of treatment, 92% of patients (n=191/208) achieved SVR12. Following 24 weeks of treatment, 96% of patients (n=165/172) achieved SVR12. Virologic relapse or breakthrough was noted in 6% of patients in the 12-week arm and 2% in the 24-week arm. AbbVie is on track to begin major regulatory submissions early in the second quarter of 2014.

December 9, 2013

Enanta Pharmaceuticals issued results of a global, multi-center, randomized, double-blind, placebo-controlled, 12-week study of ABT-333 (250mg) and ribavirin (weight-based), in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-naïve adult patients. The study population consisted of 631 GT1 treatment-naïve patients with no evidence of liver cirrhosis. 473 patients were randomized to the 3D regimen (investigational three direct-acting antiviral (3D) regimen) plus ribavirin for 12 weeks, and 158 patients were randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks. Following 12 weeks of treatment with AbbVie’s 3D regimen plus ribavirin, 96% (n=455/473) of patients achieved SVR12 based on intent-totreat analysis by which patients with missing values for any reason were considered treatment failures. In the active treatment arm, patients with GT1b infection achieved 98% SVR12 (148/151), while patients with GT1a achieved 95% SVR12 (307/322). Discontinuations due to adverse events were reported in 0.6% of patients receiving the 3D regimen. The rate of virologic relapse or breakthrough was low, occurring in 1.7% of patients receiving the 3D regimen.

April 8, 2013

ChronTech issued preliminary results from a phase II trial of ChronVac-C for hepatitis C virus (HCV) infection. This 12-week, open-label study enrolled 29 patients with chronic HCV. Subjects received two monthly vaccinations of ChronVac-C 500ug plus ribavirin and PEG-interferon-a, or placebo plus ribavirin and PEG-interferon-a, administered with Inovio’s MedPulser-DDS electroporation device. At treatment week 12, 71% of the pre-vaccinated group had less than 15 international units of HCV RNA compared to 58% in the non-vaccinated group; 65% were HCV RNA negative compared to 58% in the non-vaccinated group. There were no serious adverse events and the number of patients with moderate adverse events was statistically lower in the pre-vaccinated group than in the non-vaccinated group (p<0.05, Fishers exact test). Based on these data, ChronTech plans to initiate a phase I study of Inovio’s proprietary HCV DNA vaccine later in 2013.

March 18, 2013

Medivir reported interim results from a phase IIa trial of simeprevir for the treatment of hepatitis C virus (HCV). This randomized, open-label study, COSMOS, enrolled 80 subjects with in its first cohort with HCV and mild to moderate fibrosis (METAVIR F0-2). Subjects received simeprevir 150mg and sofosbuvir 400mg daily with or without ribavirin (RBV) for 12 or 24 weeks. Results showed 96.3% in the 12-week arm with RBV and 92.9% in the 12-week arm without RBV achieved SVR8. In the 24-week arms, SVR4 rates with RBV were 66.7% and without RBV 100%. The number of patients reaching this time point was limited, however. The drugs were well tolerated. The most frequent adverse events were fatigue, headache, insomnia and nausea in >10% of patients. Based on these data, Medivir has fully enrolled cohort 2 and will investigate similar regimens and durations in patients with METAVIR scores F3-F4.

March 11, 2013

Boehringer Ingelheim reported interim results from STARTverso 4, a phase III trial of faldaprevir for hepatitis C and HIV co-infection. This randomized, open-label trial enrolled 306 treatment-naive or relapsed subjects with hepatitis C also infected with HIV. The subjects received faldaprevir given for 12 or 24 weeks in combination with PegIFN/RBV given for 24 to 48 weeks. According to re-randomization of Early Treatment Success (ETS), subjects stopped PegIFN/RBV at 24 or 48 weeks or continued PegIFN/RBV until week 48. If no ETS, then subjects received PegIFN/RB for 48 weeks. Data showed 80% of subjects achieved early treatment success (ETS), as defined by the study protocol, when given the regimen that included faldaprevir. Results were consistent across subgroups, regardless of HIV therapy or prior HCV treatment status. Results also were reported from on-treatment virologic response at week 12, which showed 84% of all study subjects had undetectable levels of hepatitis C virus. Three additional phase III trials, part of the HCVerso program, are currently underway.

February 25, 2013

Gilead Sciences issued results from a phase III trial of nucleotide sofosbuvir plus ribavirin (RBV) in chronic hepatitis C virus (HCV). This randomized study, FUSION, enrolled treatment-experienced patients with genotype 2 or 3 chronic HCV infection who failed prior treatment. Subjects received either a 12-week (n=103) or 16-week (n=98) course of sofosbuvir 400mg/day plus RBV (1,000mg/day or 1,200mg/day). The study met its primary efficacy endpoint of superiority compared to a predefined historic control sustained virologic response (SVR) rate of 25%. In FUSION, 50% of patients (n=50/100) in the 12-week arm and 73% of patients (n=69/95) in the 16-week arm achieved SVR12 (p<0.001 for both arms). In the 12-week arm, SVR12 rates were 86% among genotype 2 and 30% among genotype 3 patients. In the 16-week arm, SVR12 rates were 94% among genotype 2 and 62% among genotype 3 patients. Among the 34% of FUSION participants who had compensated cirrhosis at baseline, 31% achieved SVR12 in the 12-week arm, and 66% achieved SVR12 in the 16-week arm. All patients in the study became HCV negative on treatment, and relapse accounted for all virologic failures. The drug was well tolerated. The most frequent adverse events were fatigue, headache, insomnia and nausea. Based on these data plus results from three other phase III studies, Gilead is on track to file regulatory applications in the U.S. and Europe in the second quarter.

February 11, 2013

Gilead Sciences released results from a phase III study of nucleotide sofosbuvir in combination with ribavirin (RBV) for the treatment of chronic hepatitis C virus (HCV) infection. This 12-week, randomized study, FISSION, enrolled 496 treatment-naïve patients with genotype 2 or 3 HCV infection. Subjects received a 12-week course of sofosbuvir 400mg once daily plus RBV 1,000mg or 1,200mg/day, or standard of care with 24 weeks of pegylated interferon alfa-2a (pegIFN) 180 μg/week plus RBV 800mg/day. The study met its primary efficacy endpoint of non-inferiority of sofosbuvir plus RBV to pegIFN plus RBV, with 67% of patients achieving a sustained virologic response (SVR) in the sofosbuvir plus RBV treatment group versus 67% in the peg-IFN plus RBV treatment group (95% CI for the difference: -7.5% to +8.0% for sofosbuvir plus RBV versus pegIFN plus RBV; redefined criterion for noninferiority was a lower bound of a two-sided 95% CI of -15%). The most frequent adverse events were fatigue, headache, nausea, insomnia and dizziness. Gilead Sciences plans to present this data, along with three other phase III studies of sofosbuvir plus RBV for HCV, at a future scientific conference.

January 21, 2013

Achillion Pharmaceuticals issued interim results from a phase IIa trial of ACH-3102 in combination with ribavirin for the treatment of patients with hepatitis C virus (HCV) infection. This open-label, pilot study enrolled eight treatment-naïve patients with chronic genotype 1b (GT 1b) HCV (IL28b genotype CC). Subjects received 225mg of ACH-3102 on day one followed by 75mg of ACH-3102 once daily on subsequent days, in combination with 1000mg-1200mg dose of ribavirin for 12 weeks. To date, results show treatment with ACH-3102 has resulted in rapid reduction in HCV RNA accompanied by normalization of liver enzymes. ACH-3102 has been well tolerated. There have been no serious adverse events, treatment discontinuations or on-treatment viral breakthrough reported to date. Based on these data, Achillion Pharmaceuticals will continue the phase IIa trial and plans to expand enrollment in the study to include non-CC GT 1b treatment-naïve patients during the first quarter of 2013, pending regulatory discussions.

December 3, 2012

Gilead Sciences released results from a phase III trial of sofosbuvir plus ribavirin (RBV) for the treatment of genotype 2 or 3 chronic hepatitis C virus (HCV) infection. This randomized, placebo-controlled study, POSITRON, enrolled 378 patients with genotype 2 or 3 chronic HCV infection who are not candidates to take interferon. Subjects received sofosbuvir 400mg once daily plus weight-based RBV twice daily (n=207), or matching placebo (n=71). Data demonstrated 78% of patients (n=161/207) remained HCV RNA undetectable 12 weeks after completing therapy (SVR12). The safety profile of sofosbuvir was similar to that observed in previous studies, and there were few treatment discontinuations due to adverse events. In the small percentage of patients with cirrhosis at baseline who received sofosbuvir/RBV, 61% achieved SVR12. All patients receiving sofosbuvir/RBV became HCV RNA negative on treatment and relapse accounted for all virologic failures, while no patient in the placebo group achieved an SVR12. The drug was well tolerated. The most frequent adverse events were fatigue, nausea, headache, insomnia, pruritis and anemia. Based on these data, Gilead Sciences expect to submit its first regulatory filings for sofosbuvir by mid-2013.

November 19, 2012

Merck released results from a phase II trial of MK-5172 for the treatment of chronic hepatitis C virus (HCV). This multi-center, double-blind, randomized, active-controlled, dose-ranging study enrolled 332 treatment-naïve patients with HCV genotype 1 infection. Subjects received MK-5172 100mg QD, 200mg QD, 400mg QD or 800mg QD in combination with peginterferon alfa-2b 1.5μg/kg weekly and ribavirin 600-1,400mg QD for 12 weeks. Subjects then received only peginterferon and ribavirin regimens for another 12 or 36 weeks, depending on response to treatment. Subjects in the active-control group received a four-week lead in with peginterferon and ribavirin regimens, followed by a regimen of boceprevir. Results showed the MK-5172 regimens had rates of the complete early viral response (cEVR) that ranged from 82.8% to 93%, versus the control rate of 74.2%. Of the patients randomized to the MK-5172 arms, 2.3% met the protocol-defined criteria for virologic failure: one patient was re-infected with genotype 3 infection; and four patients had no detectable (n=3) or low (n=1) levels of MK-5172 at time of failure and for a period of time prior. The drug was well tolerated. The most frequent adverse events were elevation of ALT/AST levels.

August 13, 2012

Achillion Pharmaceuticals issued results from a phase II trial of >strong>sovaprevir in combination with pegylated interferon and ribavirin for the treatment of hepatitis C virus (HCV). This randomized, combination, dose-escalation study enrolled 58 patients with genotype 1 HCV. Subjects received 200mg, 400mg or 800mg of sovaprevir once daily, as well as pegylated interferon and ribavirin (P/R) for 12 weeks, followed by an additional 12 or 36 weeks of P/R. The data showed positive sustained viral response (SVR4) results: 90% in the 200mg dose group, 85% in 400mg and 100% 800mg. Sovaprevir was well tolerated in all dose groups. The most frequent adverse events were consistent with P/R treatment. Based on these data, Achillion plans on moving to combination studies of and ACH-3102, another of their novel drugs, by the end of the year.

June 25, 2012

CytoPharm and Amarillo Biosciences reported results from a phase II trial of interferon-alpha lozenges for the treatment of thrombocytopenia in patients with hepatitis C virus. This randomized, dose-ranging study enrolled 169 patients in viral remission who had just completed at least 24 weeks of treatment with injectable interferon-alpha (IFNa) and Ribavirin. Subjects received oral lozenges containing 500 or 1500 international units (IU) of natural human IFNa or matching placebo for 24 weeks, followed by 24 weeks of untreated observation. At completion of the study, 81% of subjects who received 500IU lozenges normalized their mean platelet count versus only 42% in the placebo group. In the 40% of subjects who had mild liver fibrosis, only 12% of the 500IU arm experienced virological relapse by the end of the study, compared to 32% in the placebo group—a 63% reduction in relapse rate. The drug was well tolerated. Phase III studies are currently underway.

April 23, 2012

Boehringer Ingelhiem reported interim results were reported from a phase IIb trial of BI 201335 plus BI 207127 for hepatitis C. This open-label, randomized trial, SOUND-C2, enrolled 362 treatment-nave subjects with chronic genotype-1 HCV infection. The subjects were randomized into five interferon-free treatment groups, each with 120mg BI 201335 once daily (QD) and variable dosing of BI 207127 and treatment durations: BI 207127 600mg three times daily (TID) plus ribavirin (RBV) for 16 weeks; BI 207127 600mg TID plus RBV for 28 weeks; BI 207127 600mg TID plus RBV for 40 weeks; BI 207127 600mg twice daily (BID) plus RBV for 28 weeks or BI 207127 600mg TID without RBV for 28 weeks. Overall, 68% of the subjects achieved sustained viral response 12 weeks after the end of treatment (SVR12) and after 16 weeks of interferon-free treatment, SVR12 was achieved in 59% of subjects.

Bristol-Myers Squibb and Gilead released interim results from a phase II trial of GS7977 plus daclatasvir for the treatment of hepatitis C. Results are from 88 treatment-nave subjects with hepatitis C genotypes 1, 2 and 3 who were divided into six treatment groups evaluating three different dosing schedules: a seven-day lead-in dose of GS-7977 followed by daclatasvir (DCV) plus GS-7977 for 23 weeks; DCV plus GS-7977 for 24 weeks or DCV plus GS-7977 plus ribavirin for 24 weeks. Overall, 100% of subjects achieved viral load below the lower limit of quantification at week four on treatment. In the genotype 1 HCV treatment groups, 100% achieved sustained virologic response through four weeks off-treatment (SVR4). In the genotypes 2 and 3 treatment groups, 91% (40/44) of subjects achieved SVR4. The most frequent adverse events were fatigue, headache and nausea.

February 27, 2012

Vertex issued interim results from a phase II study evaluating a treatment regimen of VX-222 in combination with Incivek (telaprevir), Pegasys (pegylated-interferon alfa-2a) and Copegus (ribavirin) for genotype 1 hepatitis C. This trial, ZENITH enrolled 152 treatment nave subjects who received varying combinations of the drug regimen. These interim data are from two treatment arms who received an interferon-free (all-oral) treatment regimen of VX-222 in combination with telaprevir and ribavirin. Interim data showed that viral loads were below the lower limit of quantification (< 25 IU/mL: < LLOQ) for 80% (37/46) of subjects at week two and 83% (38/46) of subjects at week 12. The three drug regimen was generally well-tolerated.

January 16, 2012

Idenix released interim results from a phase IIb trial of IDX184 for the treatment of hepatitis C. This randomized, double-blind parallel group trial enrolled treatment-nave subjects with genotype 1 chronic hepatitis C infection. The subjects received either 50 mg or 100 mg of IDX184 administered once-daily for 12 weeks, each arm in combination with pegylated interferon and ribavirin (PegIFN/RBV). The first 31 subjects have completed 28 days of treatment. Rapid virologic response (RVR) results showed that 73% of subjects in the 100 mg IDX184 arm and 63% in the 50 mg arm had undetectable virus at 28 days. Currently 87% of subjects in the 100 mg arm and 94% in the 50 mg arm have undetectable virus at a median of eight weeks of treatment. There were no virologic breakthroughs observed in the study to date. IDX184 was well-tolerated and were no serious adverse events associated with therapy.

November 14, 2011

Boehringer Ingelheim issued interim results from a phase IIb trial of BI 201335 plus BI 207127 for hepatitis C. This open-label, randomized trial, SOUND-C2, enrolled 362 treatment-nave subjects with genotype 1 HCV. The subjects were randomized into five interferon-free treatment groups; all arms received 120mg BI 201335 once daily (QD), all arms but one received ribavirin, and each arm had a different dose of BI 207127: 600mg three times daily (TID) for 16 weeks, 28 weeks or 40 weeks; 600mg twice daily (BID) for 28 weeks; 600mg TID without RBV for 28 weeks. All five treatment arms showed high virologic response rates through week 12, defined by measuring the level of HCV RNA. Of the subjects who received BI 201335 QD + BI 207127 TID or twice daily BID with RBV, 70 to 76% achieved undetectable HCV RNA at week 12, with 13 to 21% of subjects developing a viral load breakthrough during treatment. Of the subjects who received BI 201335 QD + BI 207127 TID without RBV, 57% achieved viral response at week 12. The combination treatment was generally well tolerated.

Bristol-Myers Squibb reported interim results from a phase IIb trial of daclatasvir for hepatitis C. This randomized, double-blind, placebo-controlled study, COMMAND-1, enrolled 395 subjects, 365 with HCV genotype 1 and 30 with HCV genotype 4. The subjects were randomized to receive daclatasvir 20 mg once daily, 60 mg once daily or placebo, both in combination with peginterferon alfa and ribavirin. The length of therapy was dependent on treatment response. The endpoints were the proportion of subjects with extended rapid virologic response (eRVR) at weeks 4 and 12 and the proportion subjects with sustained virologic response at 24 weeks post-treatment (SVR24). Of the subjects with HCV genotype 1, 54% in each of the daclatasvir dose groups achieved eRVR versus 14% in the control group. The proportion of subjects with undetectable viral load at Week 12 was 78% and 75% in the daclatasvir 20 mg and 60 mg groups, respectively, compared with 43% in the control group. Of the subjects with HCV genotype 4, undetectable viral load at Week 12 was achieved in 58% and 100% in the daclatasvir 20 mg and 60 mg groups, respectively, compared with 50% in the control group.

October 17, 2011

Anadys reported results interim from a phase IIb trial of setrobuvir for the treatment of hepatitis C. This trial enrolled 283 treatment-nave and treatment-experienced subjects with genotype 1 HCV. The subjects received setrobuvir 200 mg twice a day or placebo, both in combination with Pegasys and Copegus, the current standard of care. These interim data are based on the proportion of subjects with undetectable virus at Week 12. In the treatment-nave population, 78% in the setrobuvir arm had undetectable virus versus 56% in the placebo arm. In the treatment-experienced population with prior partial response or relapse, 76% in the setrobuvir arm had undetectable virus versus 44% in the placebo arm. In the treatment-experienced population with prior null response, 29% had undetectable virus at week 12. No prior null responders received placebo. The viral breakthrough rate through 12 weeks on setrobuvir was low in both the treatment-nave arm (2.9%) and the treatment experienced population (3.6%). Setrobuvir was generally well-tolerated.

Biotron issued preliminary results from a phase IIa trial of BIT225 for hepatitis C. This trial enrolled 24 subjects infected with genotype 1 HCV who received BIT225 (200mg or 400mg) or placebo twice daily for 28 days, both in combination with interferon and ribavirin, standard of care. The trial was conducted at the Siriraj Hospital, Bangkok, Thailand. BIT225 in combination with interferon and ribavirin resulted in greater reductions in HCV levels compared to standard of care treatment alone. Subjects receiving the 400 mg dose of BIT225 showed the greatest levels of virus reduction, with an improvement of ~1 log over standard of care treatment.

July 25, 2011

Pharmasset released final results from a phase IIb trial of PSI-7977 for hepatitis C virus (HCV). This trial, PROTON, enrolled 121 treatment nave subjects infected with HCV genotype 1. These data are from 25 treatment-naive subjects with HCV genotype 2 or 3 were enrolled in an open label arm, receiving PSI-7977 400mg once daily with Peg-IFN/RBV for 12 weeks, with no Peg-IFN/RBV follow-up. Twenty four out of twenty four subjects (100%) who completed treatment achieved SVR24, or sustained viral response, defined as HCV RNA below the limit of detection (<15 IU/ml), 24 weeks after the completion of treatment. No subject exhibited breakthrough on treatment or relapse after treatment.

April 11, 2011

Bristol-Myers Squibb issued interim results from a phase IIb trial of PEG-Interferon lambda for hepatitis C. This randomized, controlled trial, EMERGE, enrolled 526 treatment-nave subjects with chronic hepatitis C genotypes 1, 2, 3 or 4. The subjects were placed in four dose groups: PEG-Interferon lambda 240 g, 180 g or 120 g or PEG-Interferon alfa 180 g, both in combination with ribavirin. The primary endpoint was complete early viral response (cEVR) at week 12. The subjects with HCV genotype 1 and 4 and treated with PEG-Interferon lambda achieved statistically significant (p<0.05) higher rates of cEVR versus PEG-Interferon alfa at all doses (lambda 240 g: 56.3%, lambda 180 g: 55.9%, lambda 120 g: 55.0% versus alfa: 37.9%). In subjects with HCV genotype 2 and 3, treatment with all doses of PEG-Interferon lambda achieved cEVR rates similar to PEG-Interferon alfa. Rates of serious adverse events were similar across treatment arms up to week 12.

March 7, 2011

Vertex and Tibotec reported interim results from a phase II trial evaluating telaprevir for hepatitis C and HIV co-infection. This two-part (A and B), randomized, double-blind, placebo-controlled, parallel group trial enrolled 60 subjects infected with both genotype 1 hepatitis C virus and human immunodeficiency virus. The subjects received either 12 weeks of telaprevir or placebo in combination with peginterferon alfa-2a and ribavirin, followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. Part A (n≡13) of the study enrolled subjects who were not receiving antiretroviral therapy for the treatment of HIV. Part B (n≡47) enrolled subjects who were being treated for HIV with either Atripla (n≡24) or a Reyataz-based regimen (n≡23). Preliminary data form both arms (n≡59) showed that 70% of the subjects receiving the telaprevir-based combination therapy had undetectable hepatitis C virus by week four (rapid viral response) compared to 5% of the subjects receiving pegylated-interferon and ribavirin alone. A complete early viral response was seen among 68% of the telaprevir-based group versus 14% of the control group at week 12. The majority of adverse events were mild to moderate

January 10, 2011

Pharmasset released interim results from a phase IIb trial of PSI-7977 for the treatment of hepatitis C. Results are from 24 subjects with genotype 2 or 3 who received PSI-7977 at 400 mg once daily plus standard of care Peg-IFN /RBV with no additional therapy for 12 weeks. Treatment resulted in rapid viral suppression, with all subjects achieving both a rapid virologic response and remaining below the limit of detection through the end of treatment at week 12. There were no viral breakthroughs. No serious adverse events were reported. The subjects are being followed for evaluation of the primary efficacy endpoint, the proportion of subjects who achieve sustained viral response at 12 and 24 weeks after the discontinuation of therapy, SVR12 and SVR24.

November 29, 2010

Medivir issued positive interim results from an ongoing phase II trial of TMC435 for the treatment of hepatitis C. This randomized, double-blind, global study enrolled 462 genotype-1 treatment-experienced patients who received once daily treatment of TMC435 (100 mg and 150 mg) given for either 12, 24, or 48 weeks, in addition to standard of care (ribavirin and pegIFNalpha-2A). All the subjects had relapsed, achieved partial response, or had no response (null responders) to treatment with standard of care. The interim analysis is from 24 weeks. The administration of TMC435 and standard of care resulted in high response rates and antiviral efficacy in all treatment groups up to and including week 4, 12 and 24. In the relapser group, 81%, 92% and 94% of patients taking TMC435 and Peg-IFN and ribavirin achieved undetectable HCV RNA levels at week 4, week 12 and week 24, respectively. For the partial responder group 62%, 84% and 86% achieved undetectable HCV RNA levels at week 4, week 12 and week 24 respectively. The null responder group also demonstrated significant response rates with 38%, 64% and 78% achieving undetectable HCV RNA levels at week 4, week 12 and week 24 respectively. All subjects were continuing on active treatment up until week 48. TMC435 was generally safe and well tolerated.

November 8, 2010

Idera issued positive interim results from a phase I trial of IMO-2125 for the treatment of hepatitis C. This dose escalation trial has enrolled 51 subjects to date, all of who had failed previous ribavirin and pegylated interferon-alpha combination therapy. The subjects received placebo or IMO-2125 administered subcutaneously once per week for four weeks at five dose levels: 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. IMO-2125 resulted in dose-dependent increases in serum concentrations of endogenous interferon-alpha, in serum concentrations of host proteins and in cell markers of immune activation. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight subjects and seven of eight subjects, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels. IMO-2125 was well tolerated for four weeks of treatment. Additional subjects are being enrolled in this trial to evaluate twice-weekly dosing of IMO-2125.

September 13, 2010

Vertex issued positive results from a phase III trial of telaprevir for the treatment of chronic hepatitis C. This randomized, double-blind, placebo-controlled study, REALIZE (Re-treatment of Patients with Telaprevir-based Regimen to Optimize Outcomes), enrolled 662 subjects with genotype 1 HCV who had failed prior treatment with pegylated-interferon (peg-IFN) and ribavirin (RBV). The trial consisted of three 48-week trial arms: telaprevir 750 mg every eight hours (q8h) for 12 weeks in combination with standard doses of peg-IFN and RBV, followed by 36 weeks of treatment with peg-IFN and RBV alone; Delayed start arm, comprised of 4 weeks of treatment with peg-IFN and RBV, followed by telaprevir 750 mg q8h for 12 weeks in combination with standard doses of peg-IFN and RBV, followed by another 32 weeks of peg-IFN and RBV alone and a control arm with standard doses of peg-IFN and RBV dosed for 48 weeks. The primary endpoint was sustained viral response (SVR), defined as undetectable HCV RNA (less than10 IU/mL) 24 weeks after the completion of treatment. The SVR rates for the telaprevir simultaneous start arm, delayed start arm and control arm, respectively, were 83%, 88% and 24% in relapsers (p<0.0001); 59%, 54% and 15% in partial responders, (p<0.0001); and 29%, 33% and 5% in null responders, (p<<0.001). The treatment was generally well tolerated.

August 16, 2010

Vertex released positive results from a phase III trial evaluating telaprevir for hepatitis C. This open label, randomized study, ILLUMINATE, was designed to evaluate whether there is benefit to extending therapy from 24 to 48 weeks in patients with undetectable HCV at weeks four and 12 of treatment (extended rapid viral response or eRVR). The trial enrolled 540 treatment nave subjects with chronic HCV genotype 1. Those who met the eRVR criteria and who remained on treatment were randomized at week 20 to receive 24 or 48 weeks of total treatment. The primary endpoint was non-inferiority with respect to SVR rates in the 24 and 48-week treatment arms. This endpoint was reached. Sustained viral response rates of 92% and 88% were observed in the 24 and 48-week treatment groups, respectively. The relapse rates were 5.7% and 1.9%, respectively.

May 31, 2010

Vertex reported positive results from a phase III trial of telaprevir for hepatitis C virus (HCV). This global, randomized, double-blind, placebo-controlled trial, dubbed ADVANCE, enrolled approximately 1,095 treatment nave subjects infected with genotype 1 chronic HCV. In all treatment arms the subjects received 750 mg of telaprevir (or placebo) orally every eight hours (q8h), a 180 ug injection of peginterferon alfa-2a (Pegasys) once-weekly, and a 1,000 mg or 1,200 mg weight-based daily oral dose of ribavirin (Copegus). The schedules were as follows: Arm A: 12 weeks of telaprevir, pegylated-interferon and ribavirin followed by 12 or 36 weeks of only pegylated interferon and ribavirin, based on response to treatment at Week 4 and Week 12; Arm B: 8 weeks of telaprevir, pegylated-interferon and ribavirin followed by 16 or 40 weeks of only pegylated interferon and ribavirin, based on response to treatment at Week 4 and Week 12 and Arm C: 48 weeks of pegylated-interferon and ribavirin. The primary endpoint was sustained viral response (SVR), defined as the proportion of subjects with undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment. SVR was reached by 75% and 69% of the 12-week and 8-week telaprivir arms versus 44% in the placebo arm (p<0.0001). Rapid Viral Response (RVR), defined as undetectable HCV RNA four weeks after the initiation of treatment, was reached by 68%, 66% and 9%, of subjects in the 12-week telaprevir-based arm, the 8-week telaprevir-based arm and the control arm. Treatment was well tolerated.

April 26, 2010

Biolex issued positive interim results from a phase IIb trial of Locteron, a controlled-release interferon alpha for the treatment of hepatitis C. This trial enrolled 116 treatment-nave subjects with genotype-1, chronic hepatitis C. The subjects were randomized into one of four dosing cohorts, the 320, 480 or 640 μg dose of Locteron (administered once every two weeks) or a control arm consisting of standard of care, PEG-Intron (1.5 μg/kg, administered every week); all subjects received weight-based ribavirin. The treatment duration was 48 weeks. These interim results are through 36 weeks of treatment. The two highest doses of Locteron demonstrated reductions in viral loads (mean changes in HCV RNA from baseline) that were comparable to that achieved with PEG-Intron administered once per week; 41%, 52% and 50% of the subjects had undetectable HCV RNA, respectively. Treatment was well tolerated and there were no unexpected adverse events.

March 22, 2010

Human Genome Sciences reported positive interim results from a phase IIb trial of albinterferon alfa-2b for the treatment of hepatitis C. This randomized, open-label, multi-center, active-controlled, adaptive-design dose-ranging study enrolled 391 treatment-nave subjects with genotypes 2 and 3 chronic disease. The subjects were randomized into four treatment groups: albinterferon alfa-2b administered once every four weeks (900 mcg, 1200 mcg or 1500 mcg) and the active-control group, peginterferon alfa-2a (Pegasys) at the standard 180-mcg dose once every week. All subjects received 800-mg daily oral ribavirin. The treatment duration was 24 weeks. The sustained virologic response (SVR) at Week 12 following the end of treatment was 81% for the treatment group receiving 1500-mcg albinterferon alfa-2b and 82% for the treatment group receiving Pegasys. SVR rates were 76% and 75%, respectively, for the 900-mcg and 1200-mcg albinterferon alfa-2b treatment groups. Overall, the adverse event profile was generally comparable between the treatment groups.

March 1, 2010

Anadys reported positive preliminary results from a phase II trial of ANA598 for hepatitis C virus (HCV). This trial plans to enroll 90 treatment naive subjects with genotype 1 HCV. The subjects received ANA598 200 mg or 400 mg both given twice daily (bid), each with a loading dose of 800 mg bid on day one, or placebo. Both ANA598 and placebo was given in combination with standard of care (SOC), Pegasys (peginterferon alfa-2a) and Copegus (ribavirin), for 12 weeks. These 12-week data are from Cohort 1 (200 mg plus SOC) and show that 73% of the subjects achieved undetectable levels of the virus, reaching the primary endpoint of complete Early Virological Response, There were no reports of viral rebound and ANA598 was well tolerated through twelve weeks, with no serious adverse events reported. The subjects will be followed or 24 weeks after stopping therapy to determine the rate of Sustained Virological Response.

May 18, 2009

Vertex issued positive results from a phase IIb trial of telaprevir for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled four-arm study, dubbed PROVE 3, enrolled 453 subjects with genotype 1 chronic hepatitis C virus who failed prior treatment with peg-IFN. The subjects received 750 mg of telaprevir every 8 hours in one of four treatment regimes: 12 weeks of telaprevir, PEG-IFN alfa-2a and ribavirin, followed by 12 weeks of PEG-IFN-a-2a and ribavirin; 24 weeks of telaprevir and PEG-INF-a-2a; 24 weeks of telaprevir, PEG-IFN-a-2a and ribavirin, followed by 24 weeks of interferon PEG-IFN-a-2a and ribavirin; or 48 weeks of PEG-IFN-a-2a and ribavirin. Subjects in the final arm had the option to receive telaprevir if they did not respond to PEG-IFN-a-2a plus ribavirin. The primary endpoint was sustained viral response (SVR). In the 24- and 48-week telaprevir-based treatment arms, 69% and 76% of prior relapsers, respectively, achieved SVR as compared to 20% in the control arm, and 39% and 38% of prior non-responders in the 24- and 48-week telaprevir-based treatment arms, respectively, achieved SVR as compared to 9% in the control arm. In a sub-anaylsis of patients with cirrhosis, 53% and 45%, respectively, those in the 24- and 48-week telaprevir-based treatment arms achieved SVR compared to 8% in the control arm. An overall relapse rate of 13% (10 of 76 subjects) was observed in the 48-week telaprevir-based treatment regimen arm, while those in the control arm relapsed at a rate of 53% (18 of 34 subjects).

March 16, 2009

Human Genome Sciences and Novartis released positive results from a phase III trial of albinterferon alfa-2b for the treatment of hepatitis C. This randomized, multi-center, active-controlled non-inferiority study, dubbed ACHIEVE 1, enrolled 1,331 treatment-naive subjects with genotype 1 chronic hepatitis C. The subjects were initially assigned to one of three treatment groups: two groups received subcutaneously administered albinterferon alfa-2b once every two weeks at doses of 900 mcg or 1200 mcg, and an active control group received peginterferon alfa-2a (Pegasys) once weekly at a dose of 180 mcg. All groups received concomitant daily oral ribavirin. A dose modification was subsequently made for the group originally assigned to the 1200-mcg dose of albinterferon alfa-2b; they had their dose modified to 900-mcg albinterferon alfa-2b every two weeks. The treatment duration was 48 weeks. The primary endpoint was non-inferiority to peginterferon alfa-2a in terms of sustained virologic response (SVR), defined as undetectable viral load (HCV RNA<10 IU/mL) at Week 72. This primary endpoint was reached (p≡0.0008).

February 19, 2009

Romark Labs released positive results from a phase II study of controlled release nitazoxanide for the treatment of chronic hepatitis C virus (HCV). This placebo-controlled, randomized study, dubbed OPTIMA HCN-2 (OPTImizing MAnagement of Hepatitis C with Nitazoxanide), enrolled 41 treatment-naive subjects with chronic hepatitis C genotype 4. The subjects received nitazoxanide at either 675 mg or 1,350 mg or placebo twice daily for four weeks, followed by the same regimen plus standard of care with peginterferon alfa-2a (Pegasys; 180 micrograms once per week) and ribavirin (Copegus; 1,000 or 1,200 mg daily according to body weight) for 36 weeks (48 weeks for the placebo arm). In both the low and high doses of controlled release nitazoxanide, 82% and 100% of the subjects, respectively, experienced undetectable serum HCV RNA (<12 IU/mL) after 12 weeks of combination therapy, compared to 63% for the placebo arm. Rapid virologic response (HCV RNA<12 IU/mL after 4 weeks of combination therapy) was observed in 59% and 63% of the low dose and high dose arms respectively, compared with 50% for the placebo group and early virologic response (greater than or equal to 2 log10 decline in HCV RNA after 12 weeks of combination therapy) was observed in 88% and 100% of the low dose and high dose arms, respectively, compared with 63% for placebo. Controlled release nitazoxanide was well-tolerated without serious adverse events. Based on the results, Romark plans to evaluate once daily dosing of nitazoxanide in future trials.

January 12, 2009

Anadys reported positive interim results from a phase Ib study of ANA598 for the treatment of Hepatitis C. This study planned to enroll 30 treatment- naive subjects with genotype 1a and 1b disease, in the US. The subjects received placebo or ANA598 twice daily (bid) over three days, at doses of 200 mg bid, 400 mg bid or 800 mg bid. Interim data are from the first cohort (200 mg ANA598 or placebo). At the end of the treatment period, the median viral load decline was 2.5 log10 (>99%), with a range of 1.4-3.4 log10. Three of the subjects who received ANA598 were genotype 1a and demonstrated a median viral load decline of 1.6 log10, while five subjects who were genotype 1b demonstrated a median viral load decline of 2.6 log10. Treatment with ANA598 led to a rapid decline in viral load. Enrollment in the second cohort is currently underway.

November 10, 2008

GlobeImmune reported positive results from a phase II trial of GI-5005 for the treatment of hepatitis C. This randomized, multi-center study enrolled 140 subjects with HCV genotype 1 who were either treatment nave or had experienced prior treatment failures. The subjects received GI-5005 plus standard of care (pegylated-interferon plus ribavirin) or standard of care (SOC) alone. The primary endpoints were viral clearance and rapid viral response (RVR), defined as undetectable HCV RNA levels (<25 IU/ml). The treatment-nave subjects with high viral loads at baseline (> 600,000 IU/mL) saw a 2.6-fold improvement in RVR by four weeks. A significant improvement was also noted in the rate of viral reduction in the peripheral blood using viral kinetic analysis in all subjects, with a 2-fold improved slope for subjects receiving GI-5005 in addition to SOC (0.32 log10/month difference, p≡0.02). A comparable magnitude of increased viral clearance in GI-5005 treated subjects was noted in all subgroups, including the prior non-responders. Based on the results, GlobeImmune plans to continue with the development of GI-5005.

GlobeImmune reported positive results from a phase II trial of GI-5005 for the treatment of hepatitis C. This randomized, multi-center study enrolled 140 subjects with HCV genotype 1 who were either treatment nave or had experienced prior treatment failures. The subjects received GI-5005 plus standard of care (pegylated-interferon plus ribavirin) or standard of care (SOC) alone. The primary endpoints were viral clearance and rapid viral response (RVR), defined as undetectable HCV RNA levels (< 25 IU/ml). The treatment-nave subjects with high viral loads at baseline (> 600,000 IU/mL) saw a 2.6-fold improvement in RVR by four weeks. A significant improvement was also noted in the rate of viral reduction in the peripheral blood using viral kinetic analysis in all subjects, with a 2-fold improved slope for subjects receiving GI-5005 in addition to SOC (0.32 log10/month difference, p=0.02). A comparable magnitude of increased viral clearance in GI-5005 treated subjects was noted in all subgroups, including the prior non-responders. Based on the results, GlobeImmune plans to continue with the development of GI-5005.

Vertx reported positive interim results from an ongoing phase II trial of telaprevir for the treatment of hepatitis C. This open-label, randomized, parallel-group study, dubbed C208, planned to enroll 160 treatment nave subjects with genotype 1 HCV, in Europe. The subjects were randomized to 1 of 4 treatment groups and received telaprevir 750 mg three times daily (q8h) or 1125 mg twice daily (q12h) for 12 weeks in combination with Pegasys (PEG-IFN-a-2a) plus ribavirin or Pegintron (PEG-IFN-a-2b) plus ribavirin, for 24 weeks. The primary endpoint was undetectable HCV RNA at 24 weeks. Interim data of the percentage of subjects with undetectable HCV RNA at week 4 and 12 was as follows: q8h alfa-2a- 80% and 93%; q8h alfa-2b- 69% and 93%; q12h alfa-2a- 83% and 83% and q12h alfa-2b- 67% and 85%, respectively. Additional phase III trials of telaprevir are currently underway.

Vertx reported positive interim results from an ongoing phase II trial of telaprevir for the treatment of hepatitis C. This open-label, randomized, parallel-group study, dubbed C208, planned to enroll 160 treatment nave subjects with genotype 1 HCV, in Europe. The subjects were randomized to 1 of 4 treatment groups and received telaprevir 750 mg three times daily (q8h) or 1125 mg twice daily (q12h) for 12 weeks in combination with Pegasys (PEG-IFN-a-2a) plus ribavirin or Pegintron (PEG-IFN-a-2b) plus ribavirin, for 24 weeks. The primary endpoint was undetectable HCV RNA at 24 weeks. Interim data of the percentage of subjects with undetectable HCV RNA at week 4 and 12 was as follows: q8h alfa-2a- 80% and 93%; q8h alfa-2b- 69% and 93%; q12h alfa-2a- 83% and 83% and q12h alfa-2b- 67% and 85%, respectively. Additional phase III trials of telaprevir are currently underway

June 16, 2008

Vertex and Tibotec released positive interim results from a phase IIb trial of telaprevir for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled four-arm study, dubbed PROVE 3, had enrolled 453 subjects with genotype 1 chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response (SVR) with at least one prior treatment. In the interim analysis, 52% (60 of 115) of subjects randomized to receive a 24-week telaprevir-based regimen (12 weeks of telaprevir in combination with pegylated interferon (peg-IFN) and ribavirin (RBV), followed by 12 weeks of peg-IFN and RBV alone) achieved undetectable HCV RNA (less than 10 IU/mL) 12 weeks post-treatment (SVR12). In the control arm (n=114), which is evaluating 48 weeks of peg-IFN and RBV only, available data indicate that 8% of subjects had undetectable HCV RNA at week 12, and 30% had undetectable HCV RNA at week 36 on-treatment (intent-to-treat analysis). Treatment was safe and well tolerated. Based on positive results, Vertex and Tibotec plan to initiate a phase III trial in Q3 of 2008.

April 28, 2008

Octoplus issued positive results from a phase II trial of Locteron for the treatment of hepatitis C. This randomized, open-label trial, dubbed SELECT-1, enrolled thirty-two treatment-nave subjects with genotype 1 hepatitis C. The subjects received Locteron, administered once every two weeks in subcutaneous doses of 160, 320, 480 and 640 micrograms (ug), combined with oral ribavirin. There was a statistically significant dose response was observed in the study. Average viral reduction after twelve weeks of treatment was greater than four logs for each of the 640, 480 and 320 ug doses, compared to 1.8 logs for the lowest dose of 160 ug. The percentage of subjects who achieved early virologic response (EVR), defined as at least a two-log reduction in hepatitis C virus, was 100% in the 640 and 480 ug dose cohorts and 88% in the 320 ug dose cohort, compared to 37.5% in the 160 ug dose cohort. In addition, Locteron resulted in a dose-dependent increase in oligoadenylate synthetase (OAS) and neopterin, markers commonly associated with the biological effects of interferon alfa. Based on the results, Octoplus plans to initiate a phase IIb study, SELECT-2, in the fourth quarter of 2008.

March 24, 2008

Valeant issued positive results from a phase IIb trial of taribavirin for the treatment of hepatitis C. This randomized, parallel, open-label study enrolled two hundred and seventy eight treatment-nave subjects with genotype 1 virus in the United States. The subjects received taribavirin at 20 mg/kg, 25 mg/kg, and 30 mg/kg per day in combination with pegylated interferon alfa-2b or weight-based dose ribavirin (800/1000/1200/1400mg daily) and pegylated interferon alfa-2b. The primary endpoints were viral load reduction and anemia rates, defined as percentage of subjects with hemoglobin (Hgb) level < 10 g/dL, at week twelve. Treatment response to taribavirin was reached in 64.2%, 57.1% and 54.4% of the subjects, respectively, and response was seen in 51.4% of subjects in the ribavirin arms. Undetectable virus, defined as HCV RNA of less than 100 copies per mL, was reached by 41.8%, 41.4% and 25% of subjects in the taribavirin arms and 31.4% of those in the ribavirin arms. The anemia rates were 9%, 7.1% and 14.7% for the subjects in the taribavirin arms, respectively, and 24.3% of those in the ribavirin arms (p=0.022 and p=0.009 for taribavirin 20mg/kg and 25mg/kg, respectively). Treatment was well tolerated and adverse events were comparable between the taribavirin and ribavirin arms. Based on the results Valeant plans to continue this trial through forty eight weeks as planned.

November 19, 2007

Roche issued positive results from a phase IIa trial of R1626 for the treatment of hepatitis C. Subjects were randomized into one of four treatment groups: Group A: R1626 (1500 mg) twice a day + PEGASYS (180 mcg) as a subcutaneous injection every week for four weeks; Group B: R1626 (3000 mg) twice a day + PEGASYS (180 mcg) as a subcutaneous injection every week for four weeks; Group C: R1626 (1500 mg) twice a day + PEGASYS (180 mcg) as a subcutaneous injection every week + COPEGUS (1000-1200 mg) daily for four weeks and Group D: PEGASYS (180 mcg) as a subcutaneous injection every week + COPEGUS (1000-1200 mg) daily (standard of care group) for four weeks. Following the first four weeks of treatment, all subjects received PEGASYS (180 mcg) subcutaneously every week with COPEGUS (1000-1200 mg) daily for another forty-four weeks, for a total treatment duration of forty-eight weeks. The primary objectives of the study were to evaluate the four-week safety and antiviral effect of combining R1626 with PEGASYS and/or COPEGUS. Results found that 81% of the subjects treated with R1626 1500 mg twice-daily + PEGASYS + COPEGUS had an undetectable HCV viral load by week four, with a mean reduction of 5.2 log10 IU/mL. Alanine transaminase (ALT), a liver enzyme, normalized in approximately 50% of subjects in all R1626 treatment groups. Treatment was well tolerated, with adverse events mild to moderate in nature. Based on the results Roche has initiated a phase IIb trial.

November 12, 2007

Romark issued positive results from a phase II trial Alinia for the treatment of hepatitis C. This randomized, controlled trial was dubbed STEALTH C-1. The study enrolled ninety-six treatment-naive subjects with chronic hepatitis C genotype 4 who were randomized into three groups to receive either forty- eight weeks of peginterferon and ribavirin (standard of care), twelve weeks of Alinia followed by thirty six weeks of Alinia plus peginterferon (dual regimen), or twelve weeks of Alinia followed by thirty-six weeks of Alinia plus standard of care (triple regimen). An additional twenty-four interferon-experienced subjects were randomized to receive twelve weeks of Alinia followed by either the dual regimen or the triple regimen for thirty-six weeks. Subjects received 180 microgram injections of pegylated interferon once per week; Alinia was administered as one 500 mg tablet twice daily; and ribavirin was administered as 1,000 or 1,200 mg daily according to weight. At twelve weeks following the end of therapy, the treatment nave subjects who received the triple regimen showed a significantly higher sustained viral response (SVR) (HCV RNA <10 IU/mL) than those receiving the standard of care regimen (79% versus 43%, respectively; p=0.006). The subjects treated with the dual regimen showed an SVR at week 12 following the end of treatment that was not inferior to standard of care (68% versus 43%, respectively) (+25%; 95% CI: -1%, +47%). In addition, of the 24 treatment-experienced subjects, the triple regimen resulted in an SVR of 25% and the dual regimen group had an SVR of 8%, at 12 weeks post-treatment. Alinia was generally well tolerated, with an adverse event profile similar across all arms. Based on the results, Romark plans to move forward with the development of Alinia.

November 5, 2007

Flamel Technologies released positive preliminary results from a phase II trial of IFN-alpha XL for the treatment of hepatitis C. This open-label, multi-center trial enrolled subjects with chronic hepatitis C genotype I. The subjects were placed in three groups, consisting of twelve to fourteen subjects each, and received IFN-alpha XL (18 MIU), dosed twice at a seven day interval; IFN-alpha XL (27 MIU), dosed twice at a seven day interval; or Peg-Intron (1.5 micrograms / kg), dosed twice at a seven day interval. Viral load was measured regularly until seven days after the second injection. Results showed a statistically significant reduction in viral load for the arm receiving 27 MIU of IFN-alpha XL compared with placebo and a marked reduction in viral load for "non-responder" subjects who received IFN-alpha-XL compared with similar subjects who received PegIntron. Treatment was determined to be well tolerated. Based on the results, Flamel is looking for a licensing partner to take the development of IFN-alpha XL forward.

October 29, 2007

Schering-Plough announced positive initial results from a phase II trial of boceprevir for the treatment of hepatitis C. This study, dubbed HCV SPRINT-1 (HCV Serine Protease Inhibitor Therapy-1), enrolled 595 treatment-naive subjects, internationally. The subjects received one of three treatment regimens: boceprevir (800 mg TID) plus Pegintron (1.5 mcg/kg once weekly) and Rebetol (800-1400 mg daily) for 28 or 48 weeks; 4 weeks of Pegintron and Rebetol combination therapy followed by adding boceprevir to the combination for 24 or 44 weeks, each at the doses listed above and boceprevir (800 mg TID) in combination with Pegintron and low-dose Rebetol (400-1000 mg daily) for 48 weeks, compared to a control of Pegintron and Rebetol alone for 48 weeks (a standard of care). The primary endpoint was sustained virologic response (SVR). The subjects in each boceprevir arm achieved a high rate of early virologic response, with 70%, 79% and 54%, respectively, having undetectable virus (HCV-RNA) at week 12 compared to 34% in the control arm. Treatment was generally safe and well tolerated. This trial is currently ongoing.

September 17, 2007

InterMune released positive results from a phase Ia trial of ITMN-191 for the treatment of hepatitis C. This double-blind, placebo-controlled single ascending dose study enrolled healthy subjects who received single doses of ITMN-191 administered as monotherapy, with and without food. A significantly higher than anticipated plasma level of ITMN-191 was experienced by subjects in dose cohorts of ITMN-191 administered with food. Plasma levels of ITMN-191 were observed in all dose groups and pharmacokinetic modeling suggested a range of potentially efficacious doses for future multi-dose trials. All doses tested were well tolerated with adverse events mild to moderate in nature. Based on positive phase Ia results, InterMune plans to commence phase Ib multi-dose trials.

Lev Pharmaceuticals issued positive results from a phase III trial of Cinryze for the treatment of hereditary angioedema. This 24 week, double-blind, placebo controlled study enrolled 24 subjects who were randomized to receive 12 weeks of Cinryze followed by 12 weeks of placebo or 12 weeks of placebo followed by 12 weeks of Cinryze. All subjects were dosed twice weekly. The primary endpoint was met, with a 53% reduction in the number of attacks for the Cinryze group compared to placebo (p less than0.0001). In addition, Cinryze led to a 66% reduction in days of swelling (p less than0.0001) and decreases in the average severity of attacks (p=0.0008) and average duration of attacks (p=0.0004). Based on these results, Lev intends to file an amendment to a BLA currently under review by the FDA to include Cinryze for the prevention of HAE attacks.

Pharmasset and Roche reported positive results from a phase I trial of R7128 for the treatment of hepatitis C. This trial enrolled 40 subjects with chronically infected hepatitis C who had failed prior interferon therapy. Subjects received placebo or R7182 (750 mg or 1500 mg) administered either once-daily or twice-daily for 14 days as monotherapy. Subjects in the highest dose cohort (1500 mg twice daily) showed the greatest mean decrease in HCV RNA from baseline, with a mean 2.7 log10 IU/mL (>99%) decrease. There was no evidence of viral rebound in any dose cohort throughout the 14 days treatment period. Treatment was generally safe and well tolerated, with no serious adverse events reported. Based on the results Pharmasset and Roche plan to initiate a phase I/II trial of R7128 in September of 2007.

August 27, 2007

Intercell released positive interim data from a phase II trial of IC41 for the treatment of hepatitis C virus (HCV). This trial enrolled 50 treatment nave subjects with chronic HCV genotype 1. Subjects received 8 intradermal injections of the IC41 vaccine in bi-weekly intervals for 14 weeks. The primary endpoint is a statistically significant decline in HCV-RNA viral load from baseline. Interim analysis from the first 25 treated subjects showed this endpoint was achieved. In the second week after the final vaccination, a 40 % reduction of viral load (0.2 log) was observed in comparison to the baseline (p=0.0178). In a subset of subjects with high viral load (> 2 million copies/ml) before treatment, a statistically significant average decline of 60 % (0.4 log) was achieved (p=0.0168). Full results and 24 week analysis are expected in early 2008.

Targeted Genetics issued mixed results from a phase II trial of tgAAC09, a vaccine for the treatment of HIV. This double-blind, randomized, placebo-controlled trial enrolled 91 HIV-negative, healthy subjects across five sited in Africa. Subjects received two intra-muscular injections of placebo or tgAAC09 at 3 different dosage levels either six or 12 months apart. The vaccine was well tolerated, with no severe local or systemic reactions reported. However, modest, dose dependent immunogenicity was observed only at the highest dose level, with responses being directed mostly to gag. Presence of neutralizing titers to adeno-associated virus vector 2 (AAV2) at baseline did not appear to impact response to vaccination. Additional phase II trials are ongoing in Africa.

Vical reported positive results from three phase IIa trials of their plasmid DNA HIV vaccine. These studies, dubbed TRIAD, enrolled subjects across several international sites. The trials involved priming an immune response with three doses of a pDNA vaccine over a two month period and boosting the response with a single dose of adenoviral vector vaccine at six months. The vaccine was shown to be safe and well tolerated. It was effective in inducing a T-cell immune responses in up to 70% of the vaccine recipients. Based on the results, Vical plans to move forward with the development of their HIV vaccine.

August 20, 2007

Immunomedics reported positive results from a follow-up phase I/II trial of epratuzumab for the treatment of systemic lupus erythematosus (SLE). Phase I of the trial enrolled 12 subjects with SLE and analyzed the effect of epratuzumab on circulatory B-cell subsets. Results showed that epratuzumab preferentially targets naive and transitional B-cells. Phase II of the trial enrolled 11 subjects with SLE and 7 subjects without SLE. It was designed to analyze the effect of epratuzumab on the inhibition of the activation of B-cells. Epratuzumab stopped the over-activation of B-cells from SLE subjects but not normal B-cells, when activated by certain immune stimulating agents. Based on the results, Immunomedics plans to move forward with the development of epratuzumab.

ViroPharma and Wyeth announced negative results from a phase II trial of HCV-796 for the treatment of hepatitis C. This randomized, open-label trial placed subjects into one of three treatment groups: Group 1 was made up of treatment naive subjects who were to receive pegylated interferon and ribavirin (control therapy); Group 2 was made up of treatment naive subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours and Group 3 was made up of non-responding subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours. Primary outcomes included antiviral activity, the percentage of subjects with undetectable plasma HCV RNA levels at weeks 4, 12, 24, and 48 and the percentage of subjects with undetectable sustained virologic response (SVR). Interim safety data review showed elevated liver enzyme levels in 8% of HCV-796-treated subjects leading to the withdrawal of two subjects, compared with 1% in pegylated interferon plus ribavirin-treated subjects. Interim efficacy data showed that at weeks 4 and 12, 45% and 73% of treatment-naive HCV-796 plus pegylated interferon and ribavirin-treated subjects had undetectable HCV levels, compared with 7% and 39% of treatment-naive pegylated interferon and ribavirin-treated subjects, respectively. At total of 4% and 23% of HCV-796 plus pegylated interferon and ribavirin-treated subjects, previously unresponsive to treatment, had undetectable HCV levels at weeks 4 and 12, respectively. However, based on the negative safety data, ViroPharma and Wyeth discontinued the dosing of subjects enrolled in the trial.

July 30, 2007

Merck released positive results from an ongoing phase II trial of Isentress for the treatment of HIV. This multi-center, dose-ranging double-blind, randomized trial enrolled 198 treatment-naive HIV subjects who received Isentress (100mg, 200mg, 400mg, or 600 mg; each administered orally twice daily) in combination with tenofovir and lamivudine or 600 mg efavirenz dosed orally once daily in combination with the same agents. The trial was designed to compare Isentress to efavirenz in terms of sustained reductions in HIV viral RNA and improvements in CD4 cell counts from baseline. At 48 weeks, results showed 83% to 88% of subjects receiving the Isentress regimen (all doses studied) maintained reductions in HIV RNA viral load to less than 50 copies/mL. These results were comparable to the efavirenz arm, with 87% of the subjects reaching this endpoint. The mean increase from baseline in CD4 cell counts of the groups receiving Isentress ranged from 144 to 221 cells/uL, and mean increase from baseline in CD4 cell counts of the efavirenz group was 170 cells/uL. A NDA is currently under review by the FDA.

OctoPlus and Biolex announced positive preliminary results from a phase IIa trial of Locteron for the treatment of hepatitis C. This randomized, open-label trial, dubbed SELECT-1 (Safety and Efficacy of Locteron: European Clinical Trial 1), enrolled 32 treatment-naïve subjects infected with hepatitis C genotype-1. Subjects received Locteron, administered subcutaneously once every two weeks in doses of 160, 320, 480 and 640 micrograms (ug), and combined with oral ribavirin, for 12 weeks. A dose dependent response was observed, with the 320 and 480 ug doses of Locteron demonstrating a greater reduction in hepatitis C virus than the 160 ug dose at all measurement times. At 12 weeks the average viral reduction for the 320 and 480 ug doses was 4.5 and 4.2 logs, respectively, compared to 1.8 logs in the lowest dose of 160 ug. In the highest dose groups (320 and 480 ug), 63% of the subjects had an undetectable viral load compared to 13% in the lowest dose group (160 ug) and early virologic response was observed in 88% and 100% of the subjects in the 320 and 480 ug dose groups, respectively, compared to 38% in the 160 ug group. Complete results are expected in Q4, 2007, with phase IIb trials planned to commence in 2008.

Samaritan reported positive preliminary results from a phase IIb trial of SP01A for the treatment of HIV. This double-blind, placebo controlled, multi-dose study enrolled 43 subjects who were placed in three SP01A treatment groups: 200mg (200mg QD), 400mg (200mg BID), and 800mg (400mg BID), for 28 days. This monotherapy study was designed to evaluate SP01A's safety and effect on viral load, with evidence of an increasing viral load at day 11 and day 28. The mean change in viral load as measured from baseline to day 11, showed an increase of 0.3 log10 copies/ml for the 200mg/day dose group, an increase of 0.1 log10 copies/ml for the 400mg/day dose group and a decrease of 0.2 log10 copies/ml for the 800mg/day dose group. At 28 days, the percentage of subjects with a reduction in viral load was 10% for the 200mg/day group, 42% for the 400mg/day group, and 50% for the 800mg/day group. Based on the results, Samaritan plans to advance SP01A into additional trials.

June 18, 2007

Gilead reported positive results from a phase III trial of Viread (tenofovir) for the treatment of chronic hepatitis B. This randomized, double-blind trial, dubbed 102, enrolled 375 subjects who were HBeAg-negative/anti-HBe positive. Subjects were placed in a 2:1 ratio to receive either tenofovir DF (300 mg once daily) or Hepsera, an FDA approved treatment (10 mg once daily), for 48 weeks. The primary endpoint was the proportion of subjects with a complete response at week 48, defined by serum HBV DNA levels below 400 copies/mL and histologic improvement characterized by at least a two point reduction in the Knodell necroinflammatory score. At 48 weeks, 70.8% of the subjects in the Viread arm had a complete response compared to 48.8% in the Hepsera arm (p less than 0.001). Adverse events were comparable between the two arms. A second phase III trial, Study 103, is currently underway, with results expected by the end of 2007.

Idenix issued positive results from a phase II trial of valopicitabine for the treatment of hepatitis C. This three-arm, partially blinded, randomized trial enrolled 117 treatment naïve, HCV genotype-1 subjects. Subjects in arm A received 200 mg/day of valopicitabine and pegylated interferon alpha 2a; subjects in arm B received 200 mg/day of valopicitabine, weight-based dosing of ribavirin, and pegylated interferon alpha 2a; and subjects in arm C received placebo, weight- based dosing of ribavirin and pegylated interferon alpha 2a (standard of care). The primary endpoint was to assess pharmacokinetic and pharmacodynamic drug-drug interaction between valopicitabine and ribavirin after 36 days of treatment. This was achieved; valopicitabine and ribavirin when administered alone or together were within the range of 80% to 125%, indicating the lack of interaction. The secondary endpoints of antiviral activity, safety and tolerability were met as well. In the subjects treated with triple combination therapy (arm B), 72.2% achieved HCV PCR-negativity, compared to 61.5% of subjects treated with the standard of care (arm C). Treatment was generally well tolerated, with three discontinuations due to adverse events. Based on the results, Idenix plans to move forward with the development of valopicitabine combination therapy.

April 23, 2007

ViroPharma reported positive top-line results from a phase Ib trial of HCV-796, combined with pegylated interferon alfa-2b (peg-IFN), for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled, sequential-group study of ascending multiple doses enrolled 16 treatment nave subjects with chronic hepatitis C infections. The first cohorts received HCV-796 monotherapy or placebo. Subsequent cohorts received HCV-796 or placebo (100 mg, 250 mg, 500 mg or 1000 mg) every 12 hours, for 14 days. On days 1 and 7 this was combined with peglyated interferon alfa-2b (1.5 ug/kg/dose). Results revealed a positive safety and tolerability profile across all dose cohorts, with adverse events mild to moderate in nature. No dose limiting toxicities were observed. In the subjects with genotype 1 infection, the mean viral reduction from baseline ranged from 2.6 to 3.2 log10 for the combination group compared to 1.3 log10 on day 14 for peg-IFN alone. In the subjects with non-genotype 1 infection the mean viral reduction ranged from 3.5 to 4.8 log10 in the combination group versus 2.6 log10 for the peg-IFN alone group. Viral reduction greater or equal to 2.0 log10 was reached by 70% to 92% of the subjects in all the combination groups compared to 40% of the subjects receiving peg-IFN alone. ViroPharma is currently conducting phase II trials with HCV-796.

April 16, 2007

Idenix announced mixed results from two phase IIb trials of valopicitabine in combination with pegylated interferon alfa-2a (Pegasys) for the treatment of genotype 1 hepatitis C. The primary endpoint for both trials was sustained virologic response (SVR) defined as maintained viral clearance six months after treatment is stopped The first trial enrolled 173 treatment-naive subjects who were randomized into one of five treatment arms for 48 weeks. After the treatment duration, 53% of the subjects treated with 200 mg/day valopicitabine plus pegylated interferon achieved undetectable HCV levels by the TaqMan assay (<20 IU/mL). The second trial enrolled 178 treatment-experienced subjects who received various doses of valopicitabine in combination with pegylated interferon or pegylated interferon and ribavirin, for 72 weeks. SVR rates were comparable for subjects receiving valopicitabine and pegylated interferon and those receiving pegylated interferon and ribavirin. Of those treated with valopicitabine in combination with pegylated interferon, none achieved a sustained virologic response. Based on the results Idenix plans to move forward with the development of valopicitabine.

Migenixissued positive top-line results from a phase II trial of celgosivir for the treatment of hepatitis C. This trial enrolled 57 subjects, 36 who were non-responders and 21 who were partial responders to prior therapy with optimized pegylated interferon plus ribavirin. The subjects were randomized into three treatment arms: (i) celgosivir (400mg once daily) plus peginterferon alfa-2b plus ribavirin ("triple combination"); (ii) celgosivir (400mg once daily) plus peginterferon alfa-2b ("double combination"); and (iii) celgosivir placebo plus peginterferon alfa-2b plus ribavirin ("control treatment"). Of the subjects in the celgosivir triple combination arm, 42% achieved an early virologic response (EVR) rate compared to 10% in the control arm. The mean HCV viral load reduction was 1.63 log(10)for the triple combination group and versus 0.92 log(10)in the control arm. Finally, the subjects in the triple combination arm showed a more rapid onset of treatment effect as measured by VLR in the first two weeks of therapy when compared to the control arm. Based on the results Migenix plans to advance the development of celgosivir into future trials.

February 19, 2007

Peregrine issued positive results from a phase Ib trial of bavituximab for the treatment of hepatits C virus (HCV). This repeat dose, open label trial enrolled 24 subjects who were placed into four cohorts. Each cohort received four escalating doses of bavituximab (0.3, 1, 3, or 6 mg/kg of body weight) over a 10-day period and then followed for 12 weeks. Treatment was well tolerated, with no adverse events of dose limiting toxicities. Efficacy results indicated that 83% of the subjects receiving 3 mg/kg showed at least a 75% (0.6 log) reduction or better in HCV RNA levels, with an average of an 84% (0.8 log) reduction for the entire cohort. In addition, 50% of the subjects in this cohort showed signs of greater antiviral activity, with an average HCV RNA load reduction of 1 log. Peak viral load reduction was typically achieved three to seven days after the initial dose. Based on these results, Peregrine plans to advance bavituximab into new HCV trials, including combination therapy and additional dosing trials.

January 8, 2007

Vertex reported positive interim results from a phase IIb trial, dubbed PROVE-1, of VX-950 for the treatment of Hepatitis C. This four-arm, double-blind, placebo-controlled trial enrolled 250 subjects who received VX-950 or placebo, in combination with pegylated interferon-2a (peg-IFN-2a) and ribavirin (RBV). The primary objective was to assess the proportion of subjects in each study arm who achieve a sustained viral response (SVR), defined as undetectable (less than 10 IU/mL, as measured by the Roche TaqMan assay) HCV RNA 24 weeks after the completion of dosing. Treatment was well tolerated, with adverse events similar between the two groups. The adverse events reported more commonly in the VX-950 treatment group included gastrointestinal disorders and rash. Of the 74 subjects in the VX-950 arm, 65 (88%) demonstrated undetectable HCV RNA (less than 10 IU/mL; Roche Taqman), compared to 17 of 33 (52%) of patients in the placebo arm. Further results were expected to be reported in 2007.

November 6, 2006

GlobeImmune announced positive interim results from a phase Ib trial of GI-5005 for the treatment of hepatitis C infections. Results from this randomized, placebo-controlled, multi-center, dose-escalation trial were collected from the first 40 subjects. GI-5005 was administered in five weekly subcutaneous doses, followed by two monthly subcutaneous doses, in ascending dose groups. Preliminary data demonstrated that treatment was well tolerated with no serious adverse events. A statistically significant difference was seen in maximum change in ALT (alanine amino transferase) levels from baseline in all GI-5005 treated subjects compared to placebo treated subjects (p=0.03). In addition three treated subjects had viral load reductions approaching 1 log10 (0.75 log10 - 0.90 log10); no placebo patients had HCV RNA reductions > 0.65 log10. This phase Ib trial was ongoing.

Idenix reported positive interim results from a phase IIb trial of valopicitabine for the treatment of Hepatitis C. This trial enrolled 173 subjects who randomized into one of five treatment arms: valopicitabine, administered once-daily, in combination with pegylated interferon alfa-2a (Pegasys) 180 micrograms per week, pegylated interferon beginning on day 8 plus valopicitabine ramping from 400 mg to 800 mg beginning at day 29-32, followed by dosing at 800 mg; valopicitabine 200 mg beginning on day 1 plus pegylated interferon beginning on day 8, valopicitabine ramping from 400 mg to 800 mg from day 1-6, followed by dosing at 800 mg plus pegylated interferon beginning on day 8, valopicitabine 800 mg beginning on day 1 plus pegylated interferon beginning on day 8; and valopicitabine 800 mg plus pegylated interferon, both beginning on day 1. The optimal dose was determined to be 200 mg valopicitabine plus pegylated interferon, with this regimen showing the most favorable viral suppression with a low rate of side effects. At 24 weeks a mean 4.24 log10 reduction in HCV RNA viral load was achieved in those subjects receiving this combination. In addition 68% of these subjects achieved viral clearance at week 24. Phase III trials are in the process of being planned and developed.

September 18, 2006

Bioenvision issued positive results from a phase II trial of Suvus for the treatment of hepatitis C (HCV). This trial enrolled subjects with chronic HCV genotype 4a infection, who were randomized to receive 60 mg of Suvus, administered orally twice a day, for either 50 days or 100 days. Treatment was well tolerated in both groups, with the most commonly reported adverse event a slight discoloration of the feces. Treatment was efficacious for both groups as well. In the treatment group receiving Suvus for 50 days, the median viral load fell from a pre-treatment level of 7.3x10(6)/ml to 1.4x10(6)/ml, with a mean percentage decrease of 83%. In the treatment group receiving Suvus for 100 days the median viral load fell from a pre-treatment level of 6.0x10(6)/ml to 0.53x10(6)/ml, with a mean percentage decrease of 92%. Based on these positive results, Bioenvision plans to develop a US and European regulatory strategy.

Valeant reported mixed results from a phase III trial, dubbed VISER2, of Viramidine for the treatment of hepatitis C infections. This trial enrolled 1,000 subjects who received either Viramidine or ribavirin, each in conjunction with a pegylated interferon, for either 24 or 48 weeks. The subjects were than taken off treatment for 24 weeks and evaluated for two co-primary endpoints: safety (superiority to ribavirin in the incidence of anemia) and efficacy (non-inferiority to ribavirin in sustained viral response, SVR). Safety results were positive, with anemia rates in the Viramidine arm significantly lower than the ribavirin arm (6% versus 22%; p less than 0.001). However, efficacy results were negative, with overall SVR rates of 40% for the Viramidine arm and 55% for the ribavirin arms. Based on these results Valeant plans to initiate a phase IIb trial to evaluate the efficacy of Viramidine at higher doses.

May 29, 2006

SciClone has issued negative final results of their second phase III trial of Zadaxin for the treatment of hepatitis C (HCV) infections. Trial data indicated that the addition of Zadaxin to a standard regimen of pegylated interferon alpha did not significantly improve sustained viral response at 72 weeks compared to pegylated interferon alpha alone, the trial's primary endpoint. Treatment with the drug was generally well tolerated. This randomized, controlled study enrolled HCV patients across sites in the US, who received either 1.6 mg Zadaxin or placebo twice weekly, in combination with a standard regimen of 180 mcg pegylated interferon alpha once weekly. Based on these results, the company announced no further plans to develop Zadaxin for the treatment of HCV, opting instead to support its development for the treatment of malignant melanoma.

March 6, 2006

Peregrine Pharmaceuticals reported positive results of a phase I trial of Tarvacin Anti-Viral, for the treatment of hepatitis C (HCV) infections, at the Strategic Research Institute's 2nd Annual Viral Hepatitis in Drug Discovery and Development Conference in Boston. Treatment was generally well tolerated, with no serious adverse events reported, and no dose-limiting toxicity observe at any of the 4 trial doses. Overall adverse events were mild, transient and not likely to be drug related. This open-label single-ascending dose study enrolled 24 patients with refractory HCV infections, who received single ascending doses of the drug. Based on these results, the company announced plans to initiate multiple-dose and combination therapy trials of the drug later in 2006.

January 16, 2006

AVI Biopharma announced positive results from the first stage of a phase I/II trial of AVI-4065, for the treatment of HCV infections. Primary safety data yielded no serious drug-related adverse events and a positive tolerability profile. Pharmacokinetic data yielded an elimination half-life of 10-12 hours, with peak plasma drug concentration approximately 4 hours after dosing. This open-label multi-center study has enrolled 30 healthy volunteers to date, who received one of 3 doses of the drug (50, 100 or 150 mg) via subcutaneous injection daily for 14 days. Based on these results the company announced plans to open enrollment for 40 subjects in the second stage of the trial.

Vertex Pharmaceuticals issued positive results of a phase Ib study of VX-950 for the treatment of hepatitis C (HCV) infections. Patients receiving the drug and pegylated interferon alfa-2a (peg-IFN) experienced a median 5.5 log10 reduction in viral load (serum HCV RNA) at the end of treatment, and 4 of 8 patients achieved undetectable viral loads. Subjects receiving VX-950 alone experience a median reduction of 4.0 log10 at 14 days, and 1 of 8 subjects achieved undetectable viral load. Subjects receiving peg-IFN monotherapy experienced a 1.0 log10 reduction, and no patients experienced undetectable viral loads. Treatment with VX-950 was well tolerated. This randomized, blinded, placebo-controlled study enrolled 20 treatment-naïve HCV patients, who received one of three 14-day treatment regimens: 750 mg VX-950 via oral tablet thrice daily; peg-IFN monotherapy, or the combination of both drugs.

January 2, 2006

Tibotec has announced interim results of a phase IIb trial of TMC114, for the treatment hepatitis C infections. The drug was show to produce a reduction in viral load of 1 log10 or more in 64% of subjects in the highest dosing group, compared to 14% for control. Further, at 24 weeks, 39% of subjects receiving TMC114 achieved undetectable viral load, vs. 7% for control. This randomized, controlled study enrolled 278 treatment experienced patients, who received optimized background regimen plus one of 4 doses of TMC114-plus-ritonavir or an investigator-selected regimen of protease inhibitor(s). Treatment in the study was to continue through 144 weeks.

November 21, 2005

Anadys announced positive results of a phase I trial of the ANA975, their isatoribine prodrug for the treatment of HCV infections. Safety data yielded no serious adverse events and a generally positive overall tolerability profile. The drug was extensively metabolized into its active form, with peak concentrations within one hour of dosing; the highest trial dose produced serum concentrations similar to an 800 mg IV infusion of isatoribine. This open-label, single-dose study enrolled 36 subjects in the UK, who received one of three doses of the drug (400 mg, 800 mg or 1200 mg) orally on an empty stomach.

Vertex reported positive results of a phase Ib trial of VX-950, for the treatment of hepatitis C (HCV) infections. Trial data yielded positive evidence of efficacy, with 26 of 28 patients receiving the drug experiencing a reduction in plasma HCV-RNA levels of 3-log or greater within 2 days. Peak efficacy at the end of the study period was achieved with a dose of 750 mg every 8 hours; subjects receiving this dose experienced a mean reduction of 4.4- log10 (roughly a 25,000 fold reduction). Pharmacokinetic data indicated that reductions in viral RNA load were generally dose-dependent, and closely correlated with trough plasma drug concentrations. This open-label dose- ranging study enrolled 28 patients with chronic hepatitis C, under the direction of the trial's primary investigator Dr. Henk Reesink. Subjects received VX-950 monotherapy for 14 days.

October 3, 2005

Migenix has announced positive results of a phase IIa trial of their a-glucosidase I inhibitor celgosivir (MX-3253) for the treatment of hepatitis C (HCV) infections. Trial data yielded a positive tolerability profile for the drug, with no serious adverse events reported and overall adverse events that were generally mild-to-moderate in severity and reversible. Two subjects experienced reductions in viral load of 1.0 log or greater, with a peak reduction of 2.6 log (99.8%) for one of these subjects. This open-label dose-ranging study enrolled 43 HCV patients across 6 sites in Canada, who received celgosivir monotherapy at doses of 200 mg once daily, 200 mg twice daily or 400 mg once daily for 12 weeks. Based on these results the company announced plans to initiate a phase IIb combination-therapy trial of the drug in the near future.

August 29, 2005

Anadys Pharmaceuticals announced results from a phase Ib trial of isatoribine (ANA245), their investigational TLR7 Agonist for the treatment of hepatitis C. Results showed the drug demonstrated dose-dependent changes in immunologic biomarkers. Plasma viral load was significantly reduced in patients receiving 800 mg once daily for seven days. Of the 12 patients in this 800 mg dose group, 10 were infected with HCV genotype 1, difficult-to-treat with current therapies. The dose-escalating, open-label study enrolled 32 adults who were administered 200 mg, 400 mg, 600 mg and 800 mg doses of isatoribine intravenously once daily for seven days. Subjects were either HCV-treatment naive or were partial responders to or relapsed from interferon-alpha. The study was conducted at two clinical sites in Western Europe. Full results were reported the in Hepatology, the official journal of the American Association for the Study of Liver Disease.

May 23, 2005

Coley Pharmaceutical Group presented positive results of a phase Ib study of Actilon (CPG 10101), for the treatment of hepatitis C virus (HCV) infections. The drug yielded evidence of efficacy, producing a 90% (1.0 log) or greater reduction in viral load in 5 of 6 subjects at the highest dosing level. Maximum viral load decrease achieved was 1.4 log. Overall safety and tolerability were both deemed positive, and pharmacodynamic results demonstrated immunogenicity consistent with the drug's mechanism of action. This double-blind, placebo-controlled study enrolled 42 HCV patients who had failed previous therapy with interferon-alpha plus ribavirin. Subjects were randomized to one of five sequential dosing cohorts of the drug (0.25 mg, 1 mg, 4 mg, 10 mg, and 20 mg) or to placebo, via twice daily subcutaneous injection for 4 weeks.

April 18, 2005

Human Genome Sciences reported positive results of a phase II trial of Albuferon (albumin interferon-alpha), for the treatment of hepatitis C, at the 40th Annual Meeting of the European Association for the Study of the Liver. Results from the study met the primary efficacy endpoint, with a mean reduction in viral load at 28 days of 3.2 log in the 2 highest dosing cohorts; 69% (n=18) of these patients experienced a reduction of >2.0 log. Secondary efficacy measures were also positive, with 23% (n=6) of patients in those cohorts exhibiting an undetectable viral load at day 42, and the majority of high-dose subjects experiencing reductions of >0.3 log per week, a level of viral reduction previously associated with sustained virologic response. Pharmacokinetic data demonstrated prolonged serum drug circulation relative to either recombinant interferon alpha or pegylated interferon alpha, with a median elimination half-life (148 hours) supportive of dosing every 2-4 weeks. This randomized, open-label, parallel-design, dose-ranging study enrolled a total of 56 patients with interferon-alpha-nave chronic hepatitis C infections across multiple sites in Canada. Subjects received 2 subcutaneous injections of 1 of 5 dose levels of the drug (200 mcg, 450 mcg, 670 mcg, 900 mcg and 1200 mcg), with safety and efficacy follow-up through 6 weeks. Based on these results, the company announced plans to initiate a larger 48 week trial of the drug in the near future.

Idenix Pharmaceuticals announced positive interim results of a phase IIa trial of valopicitabine (NM283) for the treatment of therapy-naive genotype 1 hepatitis C infections, at the 40th Annual Meeting of the European Association for the Study of the Liver. Data demonstrated a strong efficacy profile for the drug in combination with pegylated interferon, with a mean reduction in serum HCV RNA of 4.5 log10, or more than 99.99%, in the 9 subjects reaching the interim analysis milestone thus far. For 6 of the 9 this reduction produced an undetectable viral load of < 10 IU/mL in high-sensitivity PCR assay. This randomized, approved-therapy controlled study enrolled a total of 30 subjects, who received either daily valopicitabine alone (n=12) or in combination with weekly pegylated interferon (n=18). Treatment and observation through 48 weeks was ongoing, and full data from the trial will go to support ongoing phase IIb development efforts.

March 21, 2005

ViroPharma and Wyeth announced positive results of a phase Ib proof of concept study of their orally dosed hepatitis C inhibitor HCV-086. Study results indicated that the drug produced reductions in mean viral load, as measured by plasma viral RNA concentrations, with the highest mean reduction (-0.32 log10 IU/mL) observed in the highest dosing cohort. Secondary safety and pharmacokinetic data indicated generally favorable profiles for both metrics, though the highest dosing group experienced gastrointestinal adverse events that lead to 2 study discontinuations. This double blind, placebo-controlled, study enrolled 16 patients into sequential dosing groups, with subjects randomized at each of 5 dosing levels to receive the drug (n=12) or placebo (n=4). The companies announced that though the drug did demonstrate some anti-viral efficacy, it was not significant enough to warrant continued development of the drug.

January 10, 2005

Coley Pharmaceutical reported results from both phase Ia and Ib trials of Actilon (CPG10101), for the treatment of Hepatitis C infections (HCV). Data from the Ia trial met safety and pharmacodynamic endpoints, with no drug-related serious adverse events or dose-limiting toxicities over multiple subcutaneous doses and measurable, dose-related immune responses consistent with clinically established baselines for this class of drug. Data from the Ib trial demonstrated preliminary efficacy, with one third of subjects experiencing at least a 1.0 log reduction in HCV viral RNA load. Both double-blind trials randomized subjects into one of 5 Actilon dosing cohorts (0.25, 1, 4, 10, or 20 mg); the Ib trial also enrolled a placebo cohort. The Ia trial enrolled 40 healthy volunteers, who received two injections 14 days apart, followed by a 29 day observation period. The ongoing Ib trial has evaluated 18 relapsed or intolerant HCV patients to date, with subjects receiving doses twice weekly for 4 weeks.

September 13, 2004

Vertex Pharmaceuticals has issued results of a phase I a study of their investigational treatment for Hepatitis C infection, VX-950. The trial found the drug to be safe and well tolerated, with no dose limiting toxicities observed. Maximum tolerated dose was not reached, despite single doses which produced plasma concentrations exceeding those shown to be efficacious in preclinical models; certain regimens maintained these hyper-therapeutic plasma levels for more than 12 hours. The study enrolled a total of 35 healthy subjects, and was designed to investigate the safety, tolerability and pharmacokinetics of single doses of the drug ranging from 25 mg. to 1250 mg. Pending the review of these data by regulatory authorities, Vertex expects to initiate a phase I b safety and efficacy trial of the drug in HCV patients by the end of 2004.

June 7, 2004

Idenix Pharmaceuticals reported positive results from a phase I/II trial investigating NM283, an oral HCV RNA polymerase inhibitor for the treatment of hepatitis C virus (HCV). Results demonstrated that subjects given the highest dose exposure of NM283 achieved a mean viral load reduction of 92% within 15 days of treatment. The overall safety profile for NM283 was satisfactory, with no dose-limiting toxicities. No subjects changed or discontinued treatment due to any side effects. The double blind, randomized, dose escalation study enrolled 82 subjects with the genotype 1 strain of HCV at six sites in the U.S. The study was designed to evaluate the safety, pharmacokinetics and antiviral activity of NM283 during 15 days of treatment with a two-week follow up period. Subjects were placed in one of five once-daily dosing cohorts: 50, 100, 200, 400 and 800 mg and one twice-daily dosing cohort of 200 mg. Results were reported at the 2004 Digestive Disease Week conference in New Orleans.

April 26, 2004

Valeant Pharmaceuticals reported positive interim results from an on-going phase II trial investigating oral Viramidine, a nucleoside (guanosine) analog for the treatment of chronic hepatitis C (HCV). Results showed that Viramidine demonstrated antiviral activity comparable to that of ribavirin with a lower incidence of anemia. Data showed a proportion of subjects with greater than or equal to 2 log (10) reduction or non-detectable HCV RNA was 83% for both Viramidine (800-1600 mg/day) and ribavirin. The open-label, randomized, active control study enrolled 180 treatment-naive subjects with chronic HCV at multiple sites in the U.S. Subjects received Viramidine (400, 600, 800, mg) or ribavirin (1000/1200 mg) daily for 24-week and in combination with peginterferon alfa-2a. Results were reported at the European Association for the Study of the Liver Conference in Berlin, Germany.

February 23, 2004

SciClone Pharmaceuticals reported positive results from an ongoing pilot trial investigating Zadaxin, a synthetic thymosin alpha 1 for the treatment of hepatitis C virus (HCV). Result showed that 41% of subjects tested HCV RNA negative and 50% showed a virologic response after 24 weeks with Zadaxin in combination with pegylated interferon alpha and ribavirin. The ongoing, open label trial will enroll 50 subjects who have not responded to prior therapy with interferon alpha plus ribavirin. Subjects will receive 12 months of triple therapy and will be observed for six months. Sustained response, defined as negative HCV RNA by PCR, will be measured at week 72.

February 9, 2004

Rigel Pharmaceuticals reported positive results from a phase I trial of R803, a non-nucleoside polymerase inhibitor for the treatment of Hepatitis C Virus (HCV). Results showed that R803 is well tolerated with no serious adverse effects reported. Data demonstrated that subjects treated with R803 were indistinguishable from placebo in clinical signs and symptoms, serial electrocardiography, and clinical chemistry and hematology studies. Pharmacokinetic data was also collected. The dose-escalating, placebo-controlled study enrolled 42 healthy subjects in the United Kingdom. Rigel plans to initiate a phase I/II efficacy trial in the U.S. during the second quarter of 2004 for HCV-infected patients.

November 10, 2003

Hoffmann-La Roche reported positive results from a prospective study investigating the combination of Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) for the treatment of hepatitis C. Results showed treatment demonstrated a 26% sustained virological response (SVR) in African American subjects with a sustained virological response rate for Caucasians of 39%. The study enrolled 78 African American subjects and 28 Caucasians at 11 sites in the U.S. Subjects were interferon-naive with chronic hepatitis C genotype 1 and received 180 mcg subcutaneously of Pegasys, once weekly, along with Copegus (1000 or 1200 mg/day), for 48 weeks. Early virological response was assessed at 12 weeks of therapy and SVR at week 72. Results were reported at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

Human Genome Sciences reported positive results from an ongoing phase I/II trial investigating Albuferon, a form of interferon alpha for the treatment of hepatitis C. Results demonstrated that the drug was well tolerated and is biologically active in treatment-experienced adults with chronic hepatitis C. Albuferon remained in the blood longer than is reported for recombinant interferon alpha and pegylated interferon alpha. Data showed that Albuferon exhibited a median half-life of 145 hours at doses of 80 mcg or higher compared to a reported mean half-life of 80 hours for Pegasys and 40 hours for PEG-Intron. The ongoing, multi-center, open-label, dose-escalation study enrolled 69 subjects with chronic hepatitis C who had failed previous interferon alpha treatments. Results were reported at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.

Intermune reported positive results from a clinical trial investigating Intergen (intergeron alfacon-1), an approved treatment for hepatitis C. Results showed an approximately 3-fold higher sustained response rate in the difficult to treat nonresponder population taking Infergen. The randomized, open-label, single center, parallel-group study enrolled 120 hepatitis C subjects who had not responded to standard interferon plus ribavirin combination therapy. The study evaluated the efficacy of two dosing regimens of therapy followed by Infergen plus ribavirin combination. The company plans to initiate a registration trial investigating the use of treatment.

November 18, 2002

Isis Pharmaceuticals reported positive results from a phase II trial investigating ISIS 14803 for the treatment of chronic hepatitis C. In the study, all 43 subjects initially received, through intravenous infusion, 2.5 mg/kg of ISIS 14803 three times a week for two weeks, then either 4 or 6 mg/kg of ISIS 14803 once a week for 10 weeks. Data showed that six of 17 subjects receiving ISIS 14803 (6 mg/kg) twice a week experienced viral titer reductions of 1.0 - 3.8 logs, with three of these subjects experiencing a greater than 3.0 log reduction. Data suggested that elevated levels of liver function tests, including alanine aminotransferase (ALT), might correlate with antiviral activity of ISIS 14803. In the trial, decreases in viral titers were accompanied by asymptomatic transient increases in ALT levels. The treatment of ISIS 14803 was well tolerated with no adverse events reported.

November 11, 2002

Innogenetics reported positive results from a phase II extension study, investigating their E1-based therapeutic vaccine for hepatitis C. Preliminary data demonstrated that for 79% of subjects, the overall Ishak histology score either improved or remained stable, as compared to pre-study scores and a histological improvement was seen in 38% of subjects. On average, the progression of liver fibrosis was completely halted in the study group. The trial involved a cohort of 34 subjects given a course of six 20-microgram injections with vaccine at 3-week intervals. These subjects completed the initial study and subsequently re-enrolled. Of the 25 subjects who received two complete vaccination courses, 24 underwent a liver biopsy.

January 21, 2002

Positive results were reported from a phase Ia trial of XTL-002, a fully human high-affinity monoclonal antibody for the treatment of hepatitis C virus (HCV) infections. The single-center trial was designed to evaluate a single dose of XTL-002 in chronic HCV subjects. Subjects were divided into five groups, with each group receiving 0.25, 1.0, 2.5, 10 or 40 mg of XTL-002 in a single intravenous infusion. Results showed a significant reduction of HCV viral RNA, ranging from 2 to 100 fold, in eight out of 15 subjects. XTL-002 is being developed by XTL Biopharmaceuticals.

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