Clinical Trials Resource Center

HIV Infections

October 16, 2017

Janssen Pharmaceutical announced results from the pivotal phase III EMERALD study. The study demonstrated that switching to the investigational single-tablet regimen (STR) containing darunavir 800mg, cobicistat 150mg, emtricitabine 200mg and tenofovir alafenamide 10mg (D/C/F/TAF) was non-inferior to continuing treatment with a boosted protease inhibitor (PI) plus emtricitabine and tenofovir disoproxil fumarate in human immunodeficiency virus type 1 (HIV-1) positive, virologically suppressed adults. The study was a randomized (2:1), open-label, international, multicenter, parallel-group, non-inferiority, 48-week study in adult HIV-1 infected patients who are virologically suppressed (viral load [VL] <50c/mL for two months and had no more than one VL 50c/mL and <200 c/mL allowed within 12 months before screening). 1,141 patients were randomized and treated as follows: D/C/F/TAF (n=763); control (n=378). Inclusion criteria to be enrolled in the trial included absence of history of virologic failure on darunavir, and if historical genotype was available, absence of darunavir RAMs. Through 48 weeks, cumulative virologic rebound was 2.5% (D/C/F/TAF, n=19) vs. 2.1% (control, n=8) with 12/19 in D/C/F/TAF and 4/8 in the control group re-suppressed (<50 c/mL) by the end of the evaluation period. Additionally, at week 48, virologic suppression was 94.9% (D/C/F/TAF) and 93.7% (control), and virologic failure occurred in 0.8% and 0.5%, respectively, with no discontinuations for virologic failure and no observed RAMs to any study drug through 48 weeks. An NDA was filed on September 22, 2017, to the FDA.

October 9, 2017

Gilead Sciences announced detailed 48-week results from a phase III study (Study 1878) evaluating the efficacy and safety of switching virologically suppressed HIV-1 infected adult patients from a multi-tablet regimen containing a boosted protease inhibitor (bPI) to a fixed-dose combination of bictegravir (50mg) (BIC) and emtricitabine/tenofovir alafenamide (200/25 mg) (FTC/TAF). In Study 1878, a total of 577 virologically suppressed adults with HIV taking regimens of boosted atazanavir (ATV) or darunavir (DRV) + abacavir/lamivudine (ABC/3TC) or FTC/tenofovir disoproxil fumarate (TDF) were randomized 1:1 to continue their bPI regimen or to switch to open-label coformulated BIC/FTC/TAF once daily. At the primary endpoint of week 48, switching to BIC/FTC/TAF was non-inferior to continuing on a bPI regimen with 1.7% of patients in each group having HIV-1 RNA =50 c/mL (difference: 0.0%, 95% CI: -2.5% to 2.5%, p=1.00); the proportion of patients with HIV-1 RNA <50 c/mL was 92.1% in the BIC/FTC/TAF arm and 88.9% in the bPI arm, according to FDA snapshot algorithm. No patients in the BIC/FTC/TAF arm developed treatment-emergent resistance, and one participant on DRV/ritonavir + ABC/3TC developed a treatment-emergent NRTI mutation associated with abacavir. No renal adverse events leading to discontinuations or cases of proximal renal tubulopathy occurred with BIC/FTC/TAF. The incidence of grade three or four adverse events was 4% (n=13) for the BIC/FTC/TAF arm versus 6% (n=18) for the bPI arm; the incidence of grade three or four laboratory abnormalities was 16% (n=45) for the BIC/FTC/TAF arm versus 29% (n=83) for the bPI arm. The most commonly reported adverse events (all grades) in both arms included headache, diarrhea, nasopharyngitis and upper respiratory tract infection. Gilead filed a New Drug Application for BIC/FTC/TAF with a Priority Review voucher on June 12, 2017, and the FDA set a target action date of February 12, 2018, under the Prescription Drug User Fee Act. A marketing application for BIC/FTC/TAF is also under review in the European Union and was validated by the EMA on July 13.

February 27, 2017

Gilead Sciences reported 144-week data from two phase III studies (Studies 104 and 111) evaluating the safety and efficacy of Genvoya (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir alafenamide 10mg) for the treatment of HIV-1 infection in treatment-naïve adults. In the combined analysis, a total of 1,733 treatment-naïve adults with HIV were randomized to receive either Genvoya or Stribild. At week 144, 84.2% (n=729/866) of patients taking Genvoya and 80% (n=694/867; 95% CI: 0.6% to 7.8%, p=0.021) of patients taking Stribild achieved HIV-1 RNA levels less than 50 copies/mL. Additionally, at week 144, 81.1% (n=702/866) of patients taking Genvoya and 75.8% (n=657/867; 95% CI: 1.5 to 9.2%, p=0.006) of patients taking Stribild achieved HIV-1 RNA levels less than 20 copies/mL, a secondary endpoint. At week 144, virologic failure was similar between groups (Genvoya, 4.6%; Stribild, 3.9%); the difference in overall results was driven by fewer discontinuations on Genvoya due to adverse events or other reasons not related to efficacy (Genvoya, 11.2%; Stribild, 16%). There were statistically significant fewer adverse events leading to discontinuation in the Genvoya arm compared to the Stribild arm (Genvoya, 1.3%; Stribild, 3.3%, p=0.01). The most common drug-related adverse events in both groups were nausea, diarrhea and headache.

February 21, 2017

Theratechnologies released results of a phase III trial of ibalizumab for treatment-experienced patients infected with multidrug resistant HIV-1. TMB-301 was a single arm, 24-week study of ibalizumab plus optimized background regimen (OBR). Patients receiving their current failing antiretroviral therapy (ART), or no therapy, were monitored during a seven-day control period. Thereafter, a single loading dose of 2,000mg of intravenous (IV) ibalizumab was the only ART added to their regimen. The primary efficacy endpoint was the proportion of patients achieving a 0.5 log10 decrease in HIV-1 RNA seven days after initiating ibalizumab therapy, day 14 of the study. Ibalizumab was continued at doses of 800mg IV every two weeks through 24 weeks on study treatment. A total of 40 patients have been enrolled in the study. The new data showed that patients with multidrug resistant (MDR) HIV-1 infection experienced a mean increase in CD4+ T cell of 48 cells/μL after 24 weeks of treatment with ibalizumab plus an optimized background regimen (OBR). These data supplement previously reported findings, where 83% of patients achieved a 0.5 log10 decrease in viral load from baseline seven days after the single loading dose of 2000 mg of ibalizumab (primary endpoint) and a mean reduction in viral load of 1.6 log10 over the 24 week treatment period with more than 48% of patients experiencing a viral load reduction of more than 2.0 log10. A BLA to the FDA has been submitted.

August 1, 2016

ViiV Healthcare issued results of a phase IIIb, open-label, international, multicenter study of Triumeq (dolutegravir/abacavir/lamivudine) compared with atazanavir boosted with ritonavir (ATV/r) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 495 treatment-naïve women living with HIV. Results show statistically superior viral suppression (HIV-1 RNA <50 c/mL) rates at week 48: 82% versus 71% (adjusted difference 10.5%, 95% CI: 3.1%-17.8%, p=0.005) respectively. ARIA was a non-inferiority study with a pre-specified analysis for superiority. Both non-inferiority and superiority endpoints were met, with superiority being driven by lower rates of both virological failures and discontinuations due to adverse events (AEs) in the Triumeq group. The safety profile of Triumeq was favorable compared to ATV/r plus TDF/FTC, with fewer drug-related AEs reported on the Triumeq arm (33% v. 49%); there were also fewer AEs leading to discontinuation compared to those in the ATV/r plus TDF/FTC arm (4% vs 7%). Drug-related AEs reported in the Triumeq arm included nausea (31 individuals/13%), diarrhoea (12/5%), headache (5/2%) and dyspepsia (4/2%). In the ATV/r plus TDF/FTC group, drug-related AEs included nausea (35/14%), diarrhoea (18/7%), ocular icterus (18/7%), dyspepsia (15/6%), headache (14/6%) and jaundice (13/5%).

March 7, 2016

ViiV Healthcare reported results of a phase IIb, open label study of cabotegravir and rilpivirine (Janssen Sciences Ireland UC) as a two-drug treatment for patients with HIV-1 infection who had already achieved HIV viral suppression with a three drug oral regimen of cabotegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ongoing, international, multicenter, parallel group study included 309 HIV-infected adults who had not received prior anti-retroviral treatment. Enrolled patients were suppressed virologically (HIV-1 RNA <50 c/mL) during a 20-week induction period with daily oral cabotegravir (30mg) + 2 NRTIs and subsequently randomized to one of three study arms in the maintenance period: intramuscular cabotegravir long acting formulation (400mg) + rilpivirine long acting formulation (600mg) every four weeks; intramuscular cabotegravir long acting formulation (600mg) + rilpivirine long acting formulation (900mg) every eight weeks; or oral cabotegravir (30mg) + 2 NRTIs. The primary endpoint evaluated antiviral activity and safety through 32 weeks of maintenance treatment and the study will continue up to 104 weeks of treatment. Following 32 weeks of maintenance treatment, viral suppression rates for the two drug regimen dosed every eight weeks (95%) or every four weeks (94%) were comparable to the rate observed in patients continuing with a three drug oral regimen (91%). One patient in the eight week dosing group and one patient in the oral regimen group met protocol-defined virologic failure criteria; neither patient had evidence of resistance at failure. The most common drug-related adverse event reported by patients receiving injectable study medication was injection site pain (92%), of which most cases were mild (82%) or moderate (17%) in severity. The company plans a phase III study in late 2016.

August 24, 2015

CytoDyn has issued results of a phase IIb trial of PRO 140 for HIV. PRO 140 reduces viral loads by as much as 1.8log with one dose per week. In the monotherapy study, some HIV patients are experiencing suppressed viral load for 11 months. The first self-injectable antibody, PRO 140, has documented a 98% success rate. The company has a phase III trial planned for 300 patients, expected to begin by the end of Q3 2015. The company may apply for a Breakthrough designation with the FDA and plans to submit its NDA for final approval of PRO 140 in November 2016. PRO 140’s previous Fast Track designation carries a possibility of accelerated approval.

March 16, 2015

Gilead Sciences issued results of two phase III studies of tenofovir alafenamide (TAF) for the treatment of HIV- 1 infection in treatment-naïve adults. Studies 104 and 111, extended to 144 weeks, were randomized, double-blind, controlled trials conducted among 1,733 treatment-naïve adults living with HIV. A regimen of elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and TAF 10mg (E/C/F/TAF) was found to be statistically non-inferior to Gilead’s Stribild (containing elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and tenofovir disoproxil fumarate 300mg), based on percentages of patients with HIV-1 RNA levels less than 50 copies/mL. Patients were randomized 1:1 to receive a single tablet regimen of E/C/F/TAF or Stribild. At 48 weeks, 92.4% (n=800/866) of patients taking E/C/F/ TAF and 90.4% (n=784/867; CI -0.7% to +4.7%, p=0.13) of patients taking Stribild achieved HIV RNA levels less than 50 copies/ mL. Discontinuations due to adverse events were low in both treatment arms (0.9% (n=8) for E/C/F/TAF v. 1.5% (n=13) for Stribild), with the most common side effects being diarrhea, nausea, headache and upper respiratory tract infection. Gilead filed an NDA for E/C/F/TAF with the FDA on Nov. 5, 2014.

March 2, 2015

Sangamo BioSciences issued results of a phase I/II trial of SB-728-T for HIV/AIDS. HIV-infected subjects were enrolled in six cohorts. The study evaluated the effect of increasing doses of Cytoxan preconditioning as a method to maximize engraftment of ZFN- modified cells (SB- 728-T). Cohorts 1-5 (18 subjects) were designed primarily to evaluate the safety and tolerability of escalating doses of cyclophosphamide (Cytoxan) (doses tested: 200mg, 500mg/m, 1g/m, 1.5g/m or 2g/m) administered prior to an infusion of SB-728-T (CD4 cell enriched). The sixth cohort, Cohort 3 (three subjects) was designed to evaluate a CD4/CD8 SB-728-T product post-administration of Cytoxan at the optimal dose of 1g/m. Cytoxan preconditioning at doses up to 1gm/m safely enhanced total CD4 and CCR5 modified CD4 T-cells (Cohorts 1-5). Data from Cohorts 1-5 demonstrated a dose-related increase in both total CD4 T-cell and ZFN modified CD4 T-cell engraftment in response to Cytoxan preconditioning up to 1g/m. In addition, all subjects underwent a treatment interruption (TI) and were taken off antiretroviral drugs (ART) at 16 weeks post infusion. Four subjects from Cohort 1-5 remain on long-term TI and have remained off ART for at least 40 weeks.

November 24, 2014

AbbVie reported results of a phase II study of ribavirin (RBV) in patients co-infected with genotype 1 (GT1) hepatitis C virus (HCV) and HIV-1. The ongoing, multi-center, randomized, open-label study combined three direct-acting antivirals (ombitasvir/ABT-450/ritonavir and dasabuvir) with RBV (weight-based dosing of 1000mg or 1200mg per day divided twice daily). Subjects achieved sustained virologic response rates 12 weeks post-treatment (SVR12) of 93.5% (n=29/31) and 90.6% (n=29/32), respectively. Results also showed non-cirrhotic liver transplant patients with recurrent GT1 HCV and new to treatment after transplantation achieved a SVR12 rate of 97.1% (n=33/34) and a sustained virologic response rate 24 weeks post-treatment (SVR24) of 97.1% (n=33/34). No patients discontinued treatment due to adverse events in either the 12-week or 24-week arm.

November 10, 2014

Merck issued results of a phase IIb study of doravirine, plus tenofovir/emtricitabine (TDF/FTC) compared to efavirenz plus TDF/ FTC in previously untreated patients with HIV-1 infection. The phase IIb randomized, double-blind, dose-ranging clinical trial enrolled 166 patients to receive once-daily doravirine (25mg, 50mg, 100mg and 200mg) compared to once-daily efavirenz 600mg, both in combination with TDF/FTC. The primary safety analysis from the expansion phase of the study compared the incidence of central nervous system (CNS) adverse events (AEs) by week eight in patients who received doravirine 100mg plus TDF/FTC (n=108) v. patients who received efavirenz with TDF/FTC (n=108). Additional follow-up data through 48 weeks of treatment showed a 76% (n=126/166) overall virologic response rate (HIV RNA <40c/ml) for all doravirine doses (25mg, 50mg, 100mg and 200mg) that is comparable to 71% (n=30/42) reported for patients administered efavirenz (600mg). In addition, all treatment groups showed increased CD4 cell counts relative to baseline, consistent with the 24-week findings. After 48 weeks of treatment, patients in the dose-ranging part of the study who received doravirine demonstrated a lower overall incidence of drug-related adverse events (36.7%; n=166) than those who received efavirenz (57.1%; n=42). The company plans to initiate phase III studies by the end of 2014.

October 6, 2014

Gilead Sciences issued results of two phase III trials of tenofovir alafenamide (TAF) for the treatment of HIV-1 infection in treatment-naïve adults. Study 104 and Study 111 were randomized, double-blind, 96-week clinical trials among 1,744 treatment-naïve HIV-1 infected adults with viral load greater than or equal to 1,000copies/mL. In Study 104, 867 patients were randomized (1:1) and received E/C/F/TAF (n=435) or Stribild (n=432). In Study 111, 866 patients were randomized (1:1) and received E/C/F/TAF (n=431) or Stribild (n=435). The studies demonstrated the single tablet regimen comprising elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg and TAF 10mg (E/C/F/TAF), was non-inferior to Gilead’s Stribild (elvitegravir 150mg/cobicistat 150mg/ emtricitabine 200mg/tenofovir disoproxil fumarate 30 mg) based on the proportion of patients with HIV RNA levels (viral load) of less than 50copies/mL at 48 weeks of therapy. In addition, E/C/F/TAF demonstrated more favorable renal and bone safety compared to Stribild. There was a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48, favoring the TAF-based regimen (-6.8 mL/min for E/C/F/TAF v. -10.4mL/min for Stribild in Study 104 (p<0.001); -5.7mL/min for E/C/F/TAF v. -11.9mL/min for Stribild in Study 111 (p<0.001)). Additionally, patients taking the TAF-based regimen experienced a significantly smaller median percentage decrease from baseline in lumbar spine bone mineral density compared to Stribild patients (-1.19 v. -2.67 in Study 104 (p<0.001); -1.11 v. -2.81 in Study 111 (p<0.001)) and in hip bone mineral density (-0.77 v. -3.24 in Study 104 (p<0.001); -0.74 v. -2.78 in Study 111 (p<0.001)).

September 22, 2014

Sangamo BioSciences released results of a phase I trial of SB-728-T for HIV/AIDS. The study was an open-label trial to evaluate single infusions of an escalating dose of an autologous (a patient’s own) CD4+ T-cell product genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial enrolled nine HIV-infected subjects (three cohorts of three subjects each) who had sub-optimal T-cell levels and no detectable viral load on long-term ART, so-called immunologic non-responders (INRs). Three CCR5 delta 32 heterozygote subjects have controlled VL to undetectable or <1000 copies during a treatment interruption (TI) from ART, one for more than 59 weeks (to last measurement taken). Two subjects experienced a two-log decrease in viral load from peak (with Cytoxan conditioning of 1gm/m and 1.5gm/m), which has been sustained in one subject for more than 39 weeks. Five subjects currently remain on extended TI (longer than the 16 week period defined in the protocol) with VLs <10,000 copies and CD4 counts of >500. Analyses showed a large increase in CCR5-modified cells in the long-lived T(SCM) compartment, which may explain why CCR5- modified cells from a single infusion can be detected in all subjects over a prolonged period (more than 42 months). A median 0.9 log decrease in the size of the HIV reservoir at 36 months was observed in nine of nine subjects treated, as demonstrated by measurement of HIV total DNA in PBMCs. The decrease in reservoir showed a statistically significant correlation with an improvement in CD4 count. Sangamo is conducting an ongoing phase II clinical trial, SB-728-mR-1401 (1401).

August 4, 2014

The San Francisco AIDS Foundation reported results of additional, long-term data of PrEP for HIV. The 72-week, open-label extension of iPrEx enrolled 1,603 HIV uninfected persons with an average age of 28 at 11 sites on four continents. All participants had previously taken part in randomized, blinded, placebo-controlled trials of oral PrEP. 76% of OLE participants chose to receive once-daily oral PrEP with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), while the remainder chose to participate in the study without receiving PrEP. No study participant who took PrEP four or more times per week became HIV-infected. The study measured participant use of PrEP in dried blood spots (DBS), a novel and highly sensitive biomarker of long-term PrEP. Among those receiving PrEP in the study iPrEx OLE, HIV incidence was 4.7/100PY if drug was not detected in DBS, 2.3/100PY if drug concentrations indicated use of fewer than two tablets per week, 0.6/100PY for use of two to three tablets per week and 0/100PY for use of four or more tablets per week (P<0.0001).

October 28, 2013

Tobira Therapeutics released results from a phase IIb trial of cenicriviroc (CVC) for the treatment of HIV infection. The randomized, placebo-controlled, double-blind, double-dummy, dose-finding, 48-week study enrolled 143 HIV treatment-naïve adults with CCR5-tropic HIV infection (patients with CCR5- tropic virus represent approximately 80% of the treatment-naïve HIV-infected population). At week 48, CVC 100mg or CVC 200mg plus Truvada (emtricitabine/tenofovir disoproxil fumarate) showed similar virologic success rates compared to Sustiva (efavirenz or EFV) plus Truvada (68% and 64% v. 50%, FDA Snapshot Analysis-ITT). CVC was associated with a more favorable safety and tolerability profile compared to EFV, including a lower incidence of Grade 3 or higher adverse events (AEs) (4% for all CVC-treated subjects v. 14% for EFV) and discontinuations due to AEs (1% for all CVC-treated subjects v. 21% for EFV) reported. The FDA supports initiation of phase III studies to evaluate CVC as a component of a nucleos(t)ide-sparing “backbone” of cenicriviroc/lamivudine (CVC/3TC).

July 29, 2013

Inovio Pharmaceuticals has released results from two phase I trials (HVTN 070 and HVTN 080) of Pennvax-B preventative HIV DNA vaccine, HVTN 070 without electroporation and HVTN 080 with electroporation. Both trials were multicenter, randomized clinical trials, with 070 enrolling 120 patients and 080 enrolling 48 patients. Robust T-cell responses were generated in 89% of subjects who received three vaccinations of Pennvax-B, which consists of 1mg of each of three DNA plasmids (encoding for HIV gag, pol and env proteins) along with 1mg of IL-12 DNA plasmid, followed by intramuscular electroporation with Inovio’s CELLECTRA device. Three or four vaccinations with a 2mg dose of each Pennvax-B plasmid plus 1.5mg of IL-12 DNA generated fewer responses when delivered without electroporation. Six months after vaccination, T-cell response rates remained strong and persistent in the subjects who received only three doses delivered by CELLECTRA EP. Of 24 positive CD4 or CD8 Tcell responders following the third in month three, 79% (19/24) showed persistent CD4 or CD8 T-cell responses at month nine.

December 10, 2012

Profectus BioSciences issued results from a phase I trial of its recombinant vesicular stomatitis virus (rVSV)-vectored HIV vaccine. This placebo-controlled, dose-escalation study enrolled 60 patients without HIV. Subjects received 104, 105, 106, 107 and 108 plaque-forming units of the rVSV HIV-1 gag vaccine administered by intramuscular injection. The vaccine was found to be safe at all dose levels, and the 108 PFU dose has been selected for evaluation in a follow-on clinical trial (HVTN 087). Assays conducted by Profectus confirmed that 0% of subjects had pre-existing immunity to VSV, that there was a vaccine “take” in 50/50 (100%) vaccine recipients across all dose levels and that no rVSV entered the blood stream or was shed in saliva or urine. Assays conducted by the HVTN Central Immunology Laboratories demonstrated the 108 PFU dose level induced a gag-specific cell-mediated immune (CMI) response in 62.5% of vaccine recipients. Profectus is waiting for results from its pDNA prime/rVSV boost vaccination strategy before advancing the vaccine to phase II.

November 28, 2012

Gilead Sciences released results from a phase III trial of Stribild (elvitegravir 150mg, cobicistat 150mg, emtricitabine 200mg, tenofovir disoproxil fumarate 300mg) for the treatment of HIV. This randomized, double-blind study, Study 102, enrolled treatment-naïve patients with HIV-1 infection with HIV RNA levels greater than or equal to 5,000 copies/mL. Subjects received either Stribild or Atripla (efavirenz 600mg, emtricitabine 200mg, tenofovir disoproxil fumarate 300mg). Data show Stribild was non-inferior to Atripla after two years of treatment. Results found at 96 weeks of treatment, 84% of Stribild patients (n=293/348) and 82% of Atripla patients (n=287/352) achieved HIV RNA (viral load) <50 copies/mL, based on the FDA snapshot algorithm (95% CI for the difference: -2.9% to +8.3% for Stribild versus Atripla; predefined criterion for non-inferiority was a lower bound of a two sided 95% CI of -12%). The most frequent adverse events were diarrhea, nausea, upper respiratory infection, headache, abnormal dreams, fatigue, depression and insomnia. Based on these data, Gilead Sciences has initiated a phase IIIb study evaluating Stribild compared to ritonavir-boosted atazanavir plus Truvada in more than 500 HIV-positive treatment-naïve females.

November 5, 2012

Gilead Sciences reported interim results from a phase II trial of tenofovir alafenamide fumarate (TAF) for the treatment of HIV-1 infection. This randomized, double-blind, 48-week study enrolled 170 patients with HIV RNA levels ≥5,000 copies/mL and CD4 cell counts ≥50 cells/mm3. Subjects were divided into two arms. The first arm received a once-daily tablet containing TAF 10mg, elvitegravir 150mg, cobicistat 150mg and emtricitabine 200 mg. The second arm received Stribild. Bone mineral density was assessed in all patients by DEXA scans at baseline and at week 24. Compared to Stribild, the TAF-based regimen demonstrated statistically significantly smaller reductions from baseline to week 24 in bone mineral density at the lumbar spine and hip (p<0.005). In addition, small, statistically significant differences were seen in serum creatinine and in calculated creatinine clearance between the two arms in favor of the TAF-containing regimen (p<0.02). The drug was well tolerated. Both arms demonstrated similar adverse events. Gilead plans to submit these data for presentation at a scientific conference next year. The company is also studying TAF in a second phase II trial.

July 30, 2012

Gilead Sciences released results from a phase III trial of cobicistat compared to ritonavir for the pharmacoenhancing or “boosting” of HIV therapy. This randomized, double-blind study, Study 114, enrolled 357 HIV-infected treatment-naïve patients. Subjects received a once-daily regimen of atazanavir 300mg and Truvada, plus either cobicistat 150mg or ritonavir 100mg for 192 weeks. Results found that the cobicistat regimen was non-inferior to the ritonavir regimen. At 48 weeks, the study found that 85% of the cobicistat-dosed subjects compared to 87% of the ritonavir-dosed subjects achieved HIV RNA (viral load) levels less than 50 copies/mL, based on the FDA snapshot algorithm. Mean increases in CD4 cell counts were 213 cells/mm3 for cobicistat patients and 219 cells/mm3 for ritonavir patients at 48 weeks (p=0.67). The drug was well tolerated. The most common adverse events were jaundice, ocular icterus, nausea, diarrhea, headache, nasopharyngitis, hyperbilirubinemia and upper respiratory infection. Gilead Sciences has submitted a New Drug Application to the FDA for cobicistat.

March 23, 2009

Avexa released positive long-term results from an ongoing phase IIb extension study of apricitabine (ATC) for the treatment of HIV. This is an extension of AVX-201, a 48-week study which was conducted in three segments. For the first 21 days, subjects received 600 mg or 800 mg ATC twice daily or continued on lamivudine without changing their background drug regimen. At day 21, subjects continued on ATC or lamivudine as before, but their background drugs were optimized. At week 24, all subjects were offered open label ATC 800 mg twice daily. Reported data is from 96-weeks of continuous treatment. At week 96, the number of subjects with plasma levels of HIV below the limit of detection (<400 copies/mL) was 87%. Levels of CD4 cells continued to increase; at week 96 the average number of CD4 cells was around 500 to 600 cells/L. No resistance to ATC has been identified. ATC continues to be well tolerated and most adverse events are mild or moderate in nature.

August 13, 2007

Iomai released positive results from a phase I trial of their TIM ETEC patch-based vaccine for the treatment of travelers' diarrhea caused by enterotoxigenic Escherichia coli. This safety and immunogenicity trial enrolled 19 elderly subjects and 17 young adult subjects, in Ireland. The subjects received two patches, 21 days apart, containing "heat labile" toxin, or LT, and were followed for 42 days. The trial was designed to compare the number of elderly subjects who seroconverted to the number of young adult subjects who seroconverted. Results showed that all subjects who received the Iomai patch, regardless of age, seroconverted with IgG antibodies. In addition, 18 of 19 elderly subjects and 15 of 17 adult subjects also seroconverted with IgA antibodies. The patch was well tolerated, with no treatment related adverse effects reported. Based on the results, Iomai plans to initiate phase III trials in 2008.

Roche released positive interim results from a phase IIIb trial of Invirase for the treatment of HIV. This randomized, open-label trial, dubbed GEMINI, enrolled 337 subjects internationally. Subjects received Invirase plus ritonavir or lopinavir plus ritonavir given at their approved twice-daily dosages in combination with two nucleoside reverse transcriptase inhibitors (NRTIs; emtricitabine/tenofovir), once daily. The primary endpoint was the number of subjects with an HIV-1 RNA viral load of less than 50 copies per mL of blood at week 48. Secondary endpoints included measurement of lipid safety parameters. Efficacy results at 24 weeks showed that 69.9% and 69% of subjects treated with Invirase/ritonavir and lopinavir/ritonavir, respectively, achieved undetectable HIV levels (less than 50 copies per mL of blood). The same proportion of subjects in both groups achieved undetectable of less 400 copies per mL of blood. The increases in CD4 counts were comparable in both groups, with a median increase from baseline of 127 cells per cubic mL of blood for those in the Invirase/r group, and 134 cells for subjects in the lopinavir/r group. In addition, at 24 weeks, subjects treated with Invirase/r showed a lower median increase in their total cholesterol (TC) and total triglycerides (TG) than subjects treated with lopinavir/r (increase of 17 versus 26 mg/dL for TC, and an increase of 14 versus 43 mg/dL for TG). Based on the results, Roche planned to continue with the study.

August 6, 2007

AlphaVax released positive results from a phase I trial of their influenza vaccine. This placebo-controlled, randomized, double-blind study enrolled 216 healthy subjects who received a single dose of the vaccine at one of two dose levels. Data was taken four weeks after vaccine administration. Protective HI serum antibody titers were observed in 77% of the low dose and 80% of the high dose cohorts who had pre-vaccination influenza serum antibody titers (measured by hemagglutination inhibition, or "HI") that were below levels deemed protective against influenza infection. Based on the results, AlphaVax plans to move forward with the development of their influenza vaccine.

Incyte announced positive results from a phase IIa trial of INCB9471 for the treatment of HIV. This placebo-controlled trial enrolled 23 treatment-naive or treatment-experienced HIV-infected subjects harboring R5-tropic virus. Subjects received INCB9471 200 mg once-daily or placebo for 14 days. Subjects receiving INCB9471 showed rapid and prolonged reduction in viral load with a mean maximal decline of 1.81 log10 at day 16. The viral load continued to be suppressed well beyond the 14-day dosing period, with a mean 0.81 log10 decline in viral load observed at day 28. CD4+ cell counts were stable or slightly increased over the 14 day treatment period. Based on the results, two phase IIb trials are planned for early 2008.

Pfizer reported positive results from a phase III trial of maraviroc for the treatment of HIV. This 48-week trial was dubbed MERIT (maraviroc versus Efavirenz Regimens as Initial Therapy) and enrolled CCR5-tropic HIV-1 infected subjects who had never received antiretroviral therapy and had no evidence of resistance to the drugs used in the study. MERIT was designed to compare maraviroc (300 mg twice daily) to efavirenz, standard of care, (600 mg once daily), both dosed in combination with zidovudine/lamivudine. In the full set analysis, the rates of virologic suppression were 70.6% and 73.1% for the maraviroc and efavirenz groups, respectively, for less than 400 copies/ml and 65.3% vs. 69.3%, respectively, at less than 50 copies/ml. Increases in CD4+ cell counts from baseline were also greater with maraviroc (+170 cells/mm3) than with efavirenz (+144 cells/mm3). In addition, fewer subjects in the maraviroc arm experienced Grade 3 or 4 adverse events compared to the efavirenz group. The FDA issued an approvable letter for maraviroc in June of 2007.

Schering-Plough issued positive long-term data from a phase II trial of vicriviroc for the treatment of HIV. This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration was vicriviroc (5, 10 and 15 mg) or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily. This data was from 48-weeks post-treatment. Subjects in the 10 mg and 15 mg vicriviroc treatment groups achieved a median decrease in viral load of 1.92 and 1.44 (log10 copies/mL) and a median increase in CD4 cell count of 130 and 96 (cell/uL) from baseline, respectively. Subjects in the vicriviroc groups had undetectable virus at 48 weeks (HIV-1 RNA <400/<50 copies/ml) compared to those in the placebo group and fewer subjects in the vicriviroc groups experienced virological failure compared to those in the placebo group (27% and 33% versus 86%, respectively). This randomized, double blind study enrolled 118 HIV infected, treatment-experienced subjects. Treatment administration in this trial was vicriviroc (5, 10 and 15 mg), or placebo, in combination with an optimized ritonavir-boosted protease inhibitor-containing antiretroviral regimen, once daily.

March 26, 2007

Avexa issued positive results from a phase IIb trial of apricitabine (ATC) for the treatment of HIV. This randomized, double blind trial enrolled 47 subjects who received 600mg or 800mg ATC twice daily or lamivudine twice daily, for 21 days. Treatment was well tolerated, with no drug-related serious adverse events. The primary endpoint, the change in viral load after 21 days, was met. Subjects receiving ATC achieved on average a reduction of greater than 0.8 log(10) (85%) in the level of HIV in the blood after 21 days treatment compared to a reduction of less than 0.03 log(10) in those treated with lamivudine. Based on the results, Avexa plans to move the development of ATC into phase III trials.

March 12, 2007

Tibotec reported positive interim results from a phase IIb trial of TMC278 for the treatment of HIV. This randomized, partially blinded, controlled trial enrolled 368 treatment-naïve subjects who received three once-daily doses of TMC278 (25 mg, 75 mg, and 150 mg) or efavirenz (600 mg) both in combination with Combivir or Truvada. At 48 weeks 81% (25mg), 80% (75mg) and 77% (150mg) of the subjects reached the primary endpoint of confirmed plasma viral load <50 copies/mL. This was also reached by 81% of the subjects in the efavirenz arm. Based on the results, Tibotec plans to use the 75 mg dose for upcoming phase III trial.

March 5, 2007

ZLB Behring issued positive results from a phase II/III trial of C1-INH for the treatment of hereditary angioedema (HAE). This double-blind trial, dubbed IMPACT (International Multi-centre Prospective Angioedema C1-inhibitor Trials) was conducted at several international sites. It was designed to demonstrate that C1-INH concentrate leads to faster relief of acute symptoms of abdominal and facial attacks compared to placebo. Treatment was well tolerated with no drug related adverse events. The mean time to relief of symptoms was 1.3 hours +/- 1.4 hours in all treated subjects versus 60 hours +/- 26.4 hours in all untreated subjects. The mean duration of the attacks was shortened from 88 hours in the placebo treated subjects to 40.8 hours in the treated subjects. These results were to be used as part of a NDA filing in the United States.

February 26, 2007

The Immune Response Corporation released positive preliminary results from a phase II trial of Remunne and IR-103, first and second HIV vaccine candidates. This randomized, double-blind trial enrolled 55 subjects in Italy who received intramuscular injections of Remunne, IR103 (0.1 mg), IR103 (0.5 mg), IR103 (1.0 mg), or saline every 12 weeks for 54 weeks. The primary endpoint was HIV-specific immune response. CD4+ cell counts were measured at baseline and at weeks 4, 12, 24 and 36. Initial data revealed that the two treatments stabilized CD4+ T-cell counts when compared to placebo at weeks 24 and 36. No substantial difference in efficacy was seen between the Remunne and IR-103 groups and no impact on viral load was observed as compared to placebo. Further results are expected in mid-2007 and the trial is slated to conclude in 2008.

September 5, 2006

Targeted Genetics released positive interim data from a phase I trial of tgAAC09, a potential HIV vaccine candidate based on recombinant adeno-associated virus vector serotype 2 (AAV2). This double-blind, placebo-controlled, dose-escalation study enrolled 50 subjects in Germany and Belgium and 30 subjects in India, all of who were healthy and HIV-negative. Each subject received a single intramuscular injection into the upper arm. A subset group also received a second dose of tgAAC09 to determine if repeat dosing is safe and boosts immune responses. The vaccine was determined to be safe and well tolerated at both dosing levels. Additionally, moderate immune responses were observed in the subset group who received the highest dose. A phase II trial of tgAAC09 is currently underway in South Africa, Uganda and Zambia.

ViroPharma and Wyeth reported positive preliminary data from a phase Ib trial of HCV-796, combined with pegylated interferon alfa-2b, for the treatment of hepatitis C. This randomized, double-blind, placebo-controlled, sequential-group study of ascending multiple doses enrolled 16 treatment naïve subjects with chronic hepatitis C infections. Subjects 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). Safety data revealed no dose limiting toxicities. Efficacy data after 14 days of treatment determined that, across all dose groups, the combination of HCV-796 and pegylated interferon produced a mean viral reduction of between 3.3 and 3.5 log10 (99.95% to 99.97%) compared to 1.7 log10 with pegylated interferon alone. Based on these results, ViroPharma and Wyeth planned to initiate a phase II trial of HCV-796 at 500 mg to determine further dose response.

August 21, 2006

Advancis Pharmaceutical announced positive results from a phase III trial of Amoxicillin, for the treatment of pharyngitis/tonsillitis due to Group A streptococcal infections. This double- blind, double-dummy, randomized, parallel-group, 50-center non-inferiority trial enrolled 620 subjects who received a 775 mg Amoxicillin PULSYS tablet, once a day, for 10 days or 250 mg of penicillin, four times a day, for 10 days. The trial met the primary endpoint of statistical non- inferiority with 85% of the PULSYS group achieving bacterial eradication versus 83.4% of the penicillin group. Secondary endpoints met statistical non-inferiority as well in clinical cure rates at the test-of-cure visit and bacterial eradication rates at the late post-therapy visit. Based on these results, Advancis expected to file a NDA for once-daily Amoxicillin by late 2006 or early 2007.

Enzo Biochem issued positive long term results from a phase I trial, initiated in January of 2001, of HGTV43 for the treatment of HIV. This trial enrolled 5 subjects whose stem cells were collected, treated with HGTV43 ex vivo, than re-infused. Long-term safety data were positive with treatment well tolerated and no adverse events reported. Efficacy data collected demonstrated that the engineered stem cells were able to survive long term in vivo and to produce CD4+ cell progeny containing functioning antisense genes. At 12 months post-treatment antisense RNA was present in all five subjects. At 48 months, 4 subjects were available and 3 out of the 4 had antisense RNA present and at month 60 it was present in 1 out of the 3 subjects. In all the subjects tested, anti-HIV-1 antisense RNA was found in the CD34+ bone marrow cells. Enzo is further investigating HGTV43 in phase I/II trials at this time.

Tibotec Pharmaceuticals released positive results from a phase IIb trial of TMC125 for the treatment of HIV. This dose-finding, randomized, partially-blinded study enrolled 199 adult HIV-1 infected subjects who had received prior treatment. Subjects were randomized to receive 400 mg or 800 mg bid of TMC125 (n=159) with a background regimen or best available control regimen (n=40). Safety and tolerability data results demonstrated that the most commonly reported adverse events were diarrhea (22%), pyrexia (20%) and rash (20%) for the TMC125 treated group compared with 15%, 10% and 8%, respectively, for the active control group. Serious adverse events were reported by 27% of the TMC125 group and 18% of the control group. Efficacy data revealed that mean change from baseline in viral load at week 48 for the TMC125 400 mg and 800 mg bid and active control groups was -0.88, -1.01 and -0.14 log10 copies/ml, respectively. In the subjects with NNRTI resistance, those receiving TMC125 400mg or 800mg bid in combination with an optimized background regimen the viral load production was significantly greater than in the active control at 48 weeks, p=0.018 and p=0.002, respectively. Tibotec is conducting phase III trials of TMC125 at this time.

Transport Pharmaceuticals announced positive results from a phase IIb trial of device-enhanced acyclovir for the treatment of herpes labialis. This multi-center, randomized, double blind, placebo-controlled, clinic initiated, proof-of-concept trial enrolled 200 non-immunocompromised subjects, aged 18-75 years, with histories of recurrent cold sore outbreaks (3 or more annually). Safety and tolerability profiles were positive with reported adverse events similar to placebo. Efficacy data demonstrated that the median time to healing for the treatment group was 113 hours versus 148 hours for the placebo group (p= 0.02). The sub-group of participants who were treated at the first visible onset of infection displayed a time to healing of 71 hours versus 120 hours for the placebo group (p= 0.03). Transport plans to conduct additional phase II trials in the next year.

August 7, 2006

Acambis announced results from a phase II trial of MVA3000, an investigational smallpox vaccine for subjects with whom traditional vaccination is contraindicated. Safety data yielded a positive tolerability profile, with only mild adverse events reported. These events included injection site reactions, headache, fatigue, malaise and muscle ache. Efficacy data yielded positive results as well. Of the vaccine naïve subjects who received the highest dose of MVA3000, 75% seroconverted (a 4-fold or greater increase in vaccinia virus neutralizing antibodies) after two doses. Of the previously vaccinated subjects who received the highest dose of MVA3000, 88% seroconverted after two doses. This randomized, double-blind, placebo-controlled study enrolled 590 healthy subjects; 361 of whom had never received a smallpox vaccine (vaccine naïve) and 229 of whom had previously been vaccinated against smallpox. Based on these results, additional development of MVA3000 was planned.

Cerexa announced positive top-line results of a phase II trial of ceftaroline, for the treatment of complicated skin and skin structure infections (cSSSI). Efficacy data yielded a 96.8% clinical cure rate for the subjects treated with ceftaroline, versus an 88.9% cure rate for those treated with standard therapy. The microbiological response rate for the ceftaroline group was 95.2%, compared to 85.7% for the standard therapy group. Finally, ceftaroline demonstrated activity against gram-positive and gram-negative organisms isolated from patients in the study, including 100% of MRSA isolates inhibited at 0.5 mg/L or less. Safety data revealed a positive adverse event profile, with headache the most commonly reported event; control treatment yielded incidence of interstitial nephritis-related renal failure and "Red Man" syndrome. Subjects were treated with ceftaroline or standard therapy of vancomycin, with or without adjunctive aztreonam.

Cytrx announced positive preliminary results of a phase I trial of DP6-001, their investigational HIV DNA + protein vaccine. Preliminary trial data yielded a generally positive overall tolerability profile, and bioactivity measures indicated that the vaccine elicited both HIV-specific T-cell and antibody immune responses. Low grade adverse events included pain and redness at the injection site, mild body ache and low grade fever; there was some evidence that adverse events were dose proportional. This study enrolled 34 healthy volunteers, who received either a 3-dose low dose subcutaneous or intramuscular regimen of the drug, or a 3-dose high-dose intramuscular regimen of the drug. Additional results from the study were expected later in 2006.

June 19, 2006

Ambrilia Biopharma has reported positive results of a phase Ia trial of PPL-100, their investigational protease inhibitor (PI) for the treatment of HIV/AIDS. Results from the study yielded positive safety and tolerability profiles, with no incidence of serious adverse events and an overall adverse event profile including only mild (Grade 1) events. Preliminary pharmacokinetic data yielded an absorption and elimination profile supportive of once-daily dosing utilizing an un-boosted regimen in both PI-naïve and PI-experienced patients infected with drug resistant HIV strains containing highly prevalent mutations. This single-dose-escalation study enrolled 64 healthy male volunteers across 7 dosing cohorts: five 8-patient cohorts received single doses of the drug (300 mg, 600 mg, 1200 mg, 1800 mg and 2400 mg; n=6 per dose) or placebo (n=2 per dose); one cohort investigated the effects of combining the 600 mg and 1200 mg dose with a light meal; and one cohort combined the 600 mg dose with a light meal and low dose ritonavir (100 mg). Based on these results, the company announced plans to initiate a phase Ib trial in summer 2006, with results expected before year's end.

Nventa Biopharmaceuticals issued positive results of a phase I/II trial of HspE7, their investigational vaccine for the treatment of human papillomavirus (HPV) -related high-grade anal intraepithelial neoplasia (AIN) in HIV positive patients. Trial data indicated that 33% of subjects (n=5/15) regressed to low-grade or no significant dysplasia at 48 weeks post-treatment; 3 of these subjects also became HPV negative, vs. none of the patients not responding to treatment (p=0.02). This study enrolled 15 subjects under the direction of the AIDS Malignancy Consortium at the University of California in San Francisco. Subjects received one of three doses of the drug at 4 week intervals, with disease follow-up at 8, 12, 24 and 48 weeks. The company announced plans to begin trials of a more potent formulation of the vaccine within the next year.

March 27, 2006

AnorMED issued positive results of a clinical trial, dubbed XACT, of their investigational HIV-entry inhibitor AMD070 for the treatment of HIV infections. Preliminary data from the first dosing cohort yielded positive initial efficacy, with 50% of subjects (n=4/8) experiencing significant reductions in CXCR4 viral load. Mean viral load reduction was 1.3 log. These results were considered sufficiently positive to allow initiation of enrollment and dosing in higher-dose cohorts. This open-label study planned to enroll a total of 48 patients across 4 dosing cohorts. Additional results were expected at the ICAAC annual meeting in September 2006, and the company anticipated initiating a phase IIb trial of the drug before the end of 2006.

Coley Pharmaceutical announced positive interim results of a clinical trial of Actilon (CPG 10101) for the treatment of hepatitis C (HCV) infections. Top-line results indicated that 86% (n=12/14) of subjects receiving the drug plus control therapy achieved an early viral response (>2 log reduction in serum HCV RNA levels at 12 weeks), vs. 57% (n=8/14) for control therapy alone. Further, Actilon-plus-control produced a mean HCV RNA reduction of 3.3 log at 12 weeks, vs. 2.2 log for control alone. The drug was generally well tolerated, with similar adverse events seen in both groups. This randomized, controlled study enrolled a total of 74 HCV patients, who received approved control treatment with pegylated interferon and/or ribavirin alone or in combination with Actilon. Additional results from the study were to be presented at the upcoming European Association for the Study of the Liver meeting in Vienna in April 2006.

Valeant issued negative results of a phase III trial, dubbed VISER1, of Viramidine (taribavirin) for the treatment of HCV infections. Study data failed to meet their primary non-inferiority endpoint of sustained viral response: 38% of patients in the intent to treat population achieved an SVR, compared to 52% for approved therapy with ribavirin. Secondary efficacy was established, with statistical non-inferiority established in a per-protocol analysis of patients in North America and Europe (51% vs. 56%, respectively), and in patients weighing a maximum of 75 kg (62% vs. 60%). Safety data were generally positive, and Viramidine produced significantly fewer episodes of anemia than the approved drug, the trial's primary safety endpoint (5% vs. 24%; p<0.0001). This randomized, double-blind, controlled, parallel-group study enrolled 970 treatment-naïve patients at sites in the US, Canada, Europe, Israel, New Zealand and Australia. Subjects received either a fixed dose of 600 mg Viramidine, or a weight based 1,000/1,200 mg regimen of ribavirin, all in combination with peginterferon alfa 2b, for 24 to 48 weeks (based on viral genotype). The company indicated that the drug was on track for NDA filing by the end of 2007.

February 20, 2006

Acambis has reported positive results of a phase I trial of their investigational Clostridium difficile vaccine. Evidence of immunogenicity was observed, with significant increases in anti-toxin A and anti-toxin-B specific immunoglobulin G levels noted four weeks after the fist dose at the highest dose regimen, vs. placebo. Safety and tolerability results were also positive, with no serious adverse events reported and overall adverse events including those typically associated with intramuscular vaccine administration, including injection site tenderness, pain, redness, and headache). This randomized, double-blind, placebo-controlled study enrolled 50 healthy adult volunteers.

Schering-Plough reported positive results of a phase II trial of vicriviroc, for the treatment pf HIV infections. Primary efficacy data yielded a significant mean decrease in HIV RNA levels at 2 weeks, relative to placebo (25 mg: 0.93 log10; 50 mg: 1.18; 75 mg: 1.34; vs. 0.07 for placebo; p<0.001). A significantly greater portion of patients achieved virologic breakthrough (RNA > 50 copies/ml) with the three doses of the drug (56%, n=13/23; 41%, n=9/22; and 17% n=4/23, respectively), relative to placebo at 2 weeks (4%, n=1/24; p<0.001). This randomized, placebo controlled study enrolled 92 treatment naïve patients across 22 sites in Europe and Canada, who were randomized to receive one of three doses of the drug (25 mg, 50 mg or 85 mg) or placebo once daily for 14 days, followed by a combination regimen of either vicriviroc or efavirenz, in addition to Combivir.

February 13, 2006

Gilead reported positive results of a phase I/II trial of GS 9137, their investigational HIV integrase inhibitor, for the treatment of HIV infections. This double-blind, randomized, placebo-controlled study enrolled 40 patients, who received one of 3 regimens of GS 9137 monotherapy (200 mg, 400 mg or 800 mg) twice daily, 800 mg GS 9137 once daily, 50 mg of the drug plus 100 mg ritonavir once daily, or placebo, for 10 days. Trial data yielded evidence of efficacy, with a statistically significant reduction in viral load at all doses, compared to placebo (p<0.0001). Peak reductions in viral load were seen in the 400 mg twice daily and GS 9137/ritonavir combination groups (-2.03 log10 copies/mL for each regimen, from baseline). No serious adverse events or drug-related discontinuations were noted. The company announced plans to initiate a phase II trial of the drug in the near future.

Merck announced positive interim results of a phase II trial of MK-0518, for the treatment of HIV infections. The drug was shown to offer superior efficacy in reducing HIV viral load when added to optimized background therapy (OBT), compared to OBT plus placebo at 16 weeks. Specifically, 64%-84% of subjects receiving the drug (varying by dose) achieved viral loads below 400 copies/ml, and 56%-72% achieved loads below 50 copies/ml, compared to 22% and 19% (respectively) for placebo. Treatment was generally well tolerated. This multi-center, randomized, double-blinded, dose-ranging, placebo-controlled study enrolled 167 patients currently failing anti-retroviral therapy, who received one of three doses of the drug (200 mg, 400 mg, or 600 mg) or placebo twice daily for 16 weeks, in addition to OBT.

NeurogesX announced positive results of a phase III trial, dubbed C107, of Transacin (NGX-4010), for the treatment of HIV-associated sensory neuropathy. Trial data met their primary efficacy endpoint, producing a significant decrease in daily patient reported pain score (visual analog scale) over 12 weeks, vs. control (-22.8% for all subjects, vs. -10.7%; p=0.0025). Further, 34% of subjects receiving the drug experienced a decrease in pain of at least 30%, compared to 18% for placebo (p=0.0093). The greatest reductions in pain score were seen in the short- and long-duration treatment groups (-27.7%, p=0.0007; -24.7%, p=0.0046, respectively); the reduction for the middle-duration treatment was not significant (-15.9%, p=0.257). No drug-related systemic adverse events were noted. This double-blind, randomized, controlled study enrolled 307 subjects, who received a single application of the drug (30, 60 or 90 minutes) with a 12 week evaluation follow-up and a 40 week open-label extension.

November 28, 2005

Merck reported positive results of a phase II trial of MK-0518, for the treatment of HIV-1 infections, at the European AIDS Clinical Society meeting. Trial data indicated that the drug significantly reduced viral load by 1.7log to 2.2log for all treatment groups over a 10-day treatment course relative to baseline, vs. a 0.2log reduction for placebo (p<0.001); 50% or more of subjects in all treatment groups achieved viral loads below 400 copies/ml by the end of treatment. CD4 T-cells counts did not change significantly from baseline. Tolerability data were generally positive, with no serious adverse events reported, no drug- related discontinuations; the most common adverse events were headache, fatigue and dizziness. This multi-center, randomized, double-blind study enrolled 35 ART-naïve HIV-1 patients, who received one of 4 doses of the drug (100, 200, 400, or 600 mg) or placebo twice daily for 10 days. Based on these results, Merck has initiated a dose-ranging trial comparing the efficacy of MK-0518 to the approved drug Sustiva (efavirenz) over 48 weeks.

October 31, 2005

Biolex has announced positive results of a phase I trial of BLX-883, their recombinant formulation of interferon alpha, for the treatment of hepatitis C. Safety data yielded no serious adverse events, and overall drug-related adverse events for BLX-883 and Intron A (an approved formulation of interferon alpha) were comparable. Bioactivity and immunogenicity data were also comparable. This open-label controlled study enrolled 24 subjects in the US and UK, who received one of three doses of BLX-883; the 12 subjects receiving a dose of 3 million IU also received 3 million IU Intron A.

Tanox reported positive results of a phase II trial of TNX-355, their investigational viral entry-inhibitor for the treatment of HIV infections. Study results indicated that the lower treatment level of the drug, in combination with background therapy, produced a viral load reduction of 1.16 log10, compared to 0.02 log10 for background therapy alone, in last-observation-forward analysis (p<0.001). Significance was also reached in reduction from baseline values for the combination (1.19 log10) vs. background alone (0.32 log10; p=0.002). Mean maximum reduction over the 24 week period was 1.97 log10 (p=0.002). Secondary data indicated that 56% of subjects achieved a viral-load reduction of at least 0.5 log10, and 44% achieved a reduction of at least 1.0 log10, at week 24, indicating a durable response. Mean CD4+ cell counts increased in both study arms, though the difference was non-significant between the drug and placebo. This ongoing randomized, placebo controlled study enrolled 82 tripled-class treatment-experienced HIV-1-positive patients, who were randomized 1:1:1 to receive 10 mg/kg, 15 mg/kg or placebo every 2 weeks, in addition to optimized background therapy, for 24 weeks. Treatment in this study was scheduled to continue through 48 weeks, with projected phase III initiation in 2006.

September 12, 2005

IDM Pharma has issued final results of a phase I trial of their investigational HIV vaccine EP HIV-1090 at the AIDS Vaccine 2005 International Conference in Montreal. Trial data indicated that the vaccine was safe and generally well tolerated, with no serious adverse events or serious toxicities reported and no significant decrease in median CD4+ T-Cell counts. Immunogenicity results yielded epitope-specific cytotoxic T lymphocytes in 47% of patients receiving the vaccine (n=15/32). This randomized, placebo-controlled study enrolled 40 HIV-1 patients with full suppression of viral replication on stable antiretroviral therapy. Subjects received one of four doses of the drug (0.5 mg, 1 mg, 2 mg, or 4 mg; 8 subjects at each dose) or placebo (2 subjects at each dose) at 0, 4, 8 and 16 weeks, with safety evaluations continuing through week 40.

August 1, 2005

Advancis issued negative results of their phase III trial of amoxicillin PULSYS, for the treatment of pharyngitis/tonsillitis due to Group A streptococcal infections (strep throat). Trial data did not meet their primary efficacy endpoint, failing to achieve statistical non-inferiority to penicillin in bacterial eradication at post-therapy test-of-cure visit (65.3% vs. 68.0%, respectively). The drug also failed to demonstrate secondary non-inferiority in clinical cure at the test-of-cure visit and in bacterial eradication at late post-therapy follow-up. This controlled study enrolled pediatric patients, who received one of two doses of oral amoxicillin PULSYS (475 mg or 775mg once daily) or an oral suspension of penicillin (10 mg/kg 4 times daily) for 10 days.

Pfizer issued positive results of a set of phase I/II trials of maraviroc, for the treatment of HIV infections, at the 3rd International AIDS Society Conference on Pathogenesis and Treatment. Safety results from 6 studies indicated that the drugs toxicity and tolerability was comparable to placebo at multiple dose levels. A pair of monotherapy studies indicated that the drug reduced HIV viral load by 1.6-1.84 log across multiple dose regimens (200 mg to 600 mg total daily dose) after 10 days; the degree of reduction was not dose-dependent. Absorption data indicated that the drug could be administered with or without food. The 6 safety studies enrolled 259 healthy volunteers and HIV patients, who received short term regimens of up to 300 mg maraviroc twice daily. The dose-ranging monotherapy trials treated 63 patients for 10 days.

March 14, 2005

The Immune Response Corporation has issued positive results of a pair of phase II trials of their investigational HIV vaccine Remune (RG-83894). Results from the first study (the “REMIT” study), an follow-up to a double-blind phase II trial conducted in Spain (the “STIR-2102” trial), indicated that subjects who had received the drug in both STIR-2102 and REMIT were less likely to experience an efficacy failure endpoint at 48 weeks, versus subjects receiving control therapy with Incomplete Freud’s Adjuvant (IFA) in one or both trials. A correlation was noted between both the number of doses of Remune and the magnitude HIV-specific immune response, and the length of delay of virologic failure after treatment conclusion. The second study found that Remune successfully maintained CD4+ T-cell counts through 28 weeks, while these levels declined in subjects receiving either IFA or placebo. The REMIT study enrolled 39 patients who had participated previously in the double-blind STIR-2102 trial; these subjects, who had received either Remune or IFA in STIR-2102, were re-randomized to receive one of the treatments again for 48 weeks, yielding a total of 4 treatment cohorts (Remune-Remune, n=9; Remune-IFA, n=10; IFA-Remune, n=12; or IFA-IFA, n=8). The second trial, a multi-center, single-blind, randomized study, enrolled 51 patients who received three doses of Remune (n=19), IFA (n=11) or saline (n=10) at weeks 0, 12 and 24, or a single-dose of Remune at week 0 (n=10); the disease status of all subjects , as indicated by CD4+ T-cell counts, was followed through 28 weeks. The company announced that the results of these trials would serve to support the design of registration trials in the near future.

March 7, 2005

VIRxSYS has issued interim results of an ongoing phase I trial of their investigational antisense antiretroviral drug VRX496, for the treatment of HIV infections. Trial data met their primary safety endpoints, with no treatment-related serious adverse events observed. Furthermore, significant preliminary evidence of efficacy was observed, with a single administration of the drug producing significant reductions in viral load seen among all three patients completing 1-year follow-up. Stable viral loads have been observed thus far for the 2 subjects who had not yet reached this mark. Furthermore, T-cell counts remained stable or improved for all patients. This open-label study enrolled 5 patients failing at least 2 prior courses of HAART HIV therapy, who each received a single-dose of the drug. Following these results, VIRxSYS announced plans to meet with the FDA in March 2005 to discuss the phase I results and design a phase controlled, multi-center, multi-dose trial. Also, the company expects to initiate phase II studies in Q2 2005.

February 28, 2005

Targeted Genetics, in collaboration with the International AIDS Vaccine Initiative, has issued preliminary data from a phase I trial of their investigational recombinant adeno-associated viral vector based HIV/AIDS vaccine candidate tgAAC09. Results from the ongoing study indicated that the drug met its primary safety endpoint, with no serious adverse events noted and a favorable tolerability profile. Trial doses of the vaccine did not elicit significant immune response. This double-blind, placebo-controlled, dose-escalation safety study enrolled 50 healthy, HIV-negative subjects across sites in Belgium and Germany. Subjects received a single intramuscular injection of the drug or placebo. The company announced that they were expanding the study, enrolling 30 additional healthy subjects in India, and administering a second round of treatment to a subset of patients in an effort to increase immune response, based on these initial results.

February 7, 2005

Gilead has reported preliminary data from their phase III b study the addition of combination HIV therapy with the approved drugs Viread (tenofovir disoproxil fumarate) and Emtriva (emtricitabine) to standard treatment with Sustiva (efavirenz). Results from the first 48 weeks found that the addition of the two drugs to Sustiva produced significantly superior efficacy, vs. the addition of Combivir (lamivudine 150 mg/zidovudine 300 mg). Specifically, a significantly greater portion of subjects on Viread/Emtriva achieved HIV RNA less than 400 copies/ml (84% vs. 73%; p=0.002), HIV RNA less than 50 copies/ml at week 48 (80% vs. 71%; p=0.027), and an increase from baseline in CD4 cell count (189 vs. 158 cells/mm3; p=0.002), vs. subjects receiving Combivir through week 48. The two drug combination also produced significantly fewer withdrawals due to adverse events (4% vs. 9%; p=0.019), and had generally fewer serious side effects than Combivir. This multicenter, open-label study enrolled 517 antiretroviral-naïve HIV-infected patients in the United States and Europe, who received either Viread 300 mg, Emtriva 200 mg once daily or Combivir twice daily, both in addition to once daily Sustiva 600 mg.

December 6, 2004

Viral Genetics reported results of a study of VGV-1 (TNP), for the treatment of HIV positive patients failing to respond to their second or third regimen of anti-retroviral drug therapy. Results from the trial demonstrated that the addition of VGV-1 to standard personalized antiretroviral therapy produced significant efficacy in reducing viral load. Specifically, 50% of subjects (5 of 10) achieved an undetectable viral load (<40 copies/mL) after 60 days of treatment, and 6 months of treatment produced a mean one-log drop in viral load for all subjects. The addition of VGV-1 to standard antiretroviral therapy produced no serious adverse events. This open-label study enrolled 10 HIV-positive men with disease refractory to standard therapy at a single investigative site in Mexico. The company announced plans to use this data to support ongoing efforts to find development partners and pursue IND filing in the US.

November 29, 2004

Panacos Pharmaceuticals reported preliminary results of a phase I/II proof-of-concept trial of PA-457, their viral maturation inhibitor under investigation for the treatment of HIV infections. Single doses of the drug produced preliminary evidence of efficacy, with a significant reduction in viral load (as measured by plasma viral RNA concentrations) of as much as 0.7 log10 at higher doses, compared to baseline. This pharmacokinetic and efficacy study randomized HIV-positive subjects not currently on other therapies to receive dose-ranging single doses of the drug or placebo. Panacos announced plans to initiate a multiple-dose phase IIa trial of PA-457 as once-daily monotherapy in HIV-positive subjects not on other therapy in the first half of 2005, based upon these results.

Rigel Pharmaceuticals has announced negative results of a phase I/II trial of R803, their investigational RNA polymerase inhibitor for the treatment of hepatitis C (HCV) infections. The trial failed to meet its primary endpoint, a reduction in viral load relative to baseline, though a minor trend towards improvement was seen. The company noted that R803 had exhibited poor oral bioavailability, with mean serum drug concentration reaching minimum therapeutic levels for only a few hours during the daily dosing regimen. The drug did meet all safety and tolerability endpoints, with no serious adverse events. The randomized, placebo-controlled, double-blind multiple, dose-escalating safety and pharmacokinetic study enrolled 32 HCV patients at 2 US sites, who were randomized into one of eight dosing cohorts. Rigel announced plans to continue development of the drug in a new formulation.

November 22, 2004

Auxilium Pharmaceuticals reported positive results of a clinical trial of their approved testosterone replacement gel Testim in hypogonadal HIV-positive men. Top-line results indicate that the drug was efficacious in treating symptoms of hypogonadism, with significant improvements observed in reported sex drive, erectile function, and sexual-satisfaction with sex life, as well as satisfaction with androgen therapy. These improvements in sexual function resulted in a significantly fewer Testim treated men requiring titration to a higher dose compared to men treated with AndroGel, another approved topical testosterone therapy (30% vs. 74%; p<0.05). This approved-therapy controlled study enrolled a total of 48 HIV-positive hypogonadal men who had not achieved adequate symptom relief on AndroGel.

Boehringer-Ingelheim has reported positive results of a phase III trial of tipranavir, their investigational protease inhibitor for the treatment of HIV infections. Results from a 24-week interim analysis have indicate that the drug is efficacious in reducing viral load, with a significantly greater portion of subjects receiving tipranavir plus low-dose ritonavir (T/r) achieving treatment response (a 1 log(10) or greater decrease) than in those receiving a comparator protease inhibitor plus low-dose ritonavir (CPI/r) (41.0% vs. 14.9%; p<0.001). Furthermore, subjects receiving T/r experienced a significantly greater portion of subjects achieving preset total viral load levels of 400 copies/ml and 50 copies/ml (p<0.0001), and significant greater increases in CD4+ count (p=0.02), than in subjects taking CPI/r. The randomized, approved-therapy controlled, open-label trial was designed to study the safety and efficacy of T/r versus CPI/r, in 863 treatment-experienced patients with documented protease-inhibitor resistance. This trial, along with a second phase III study, formed the basis of the company’s NDA application, submitted on October 22, 2004.<

MacroChem has announced positive results of a phase I trial of EcoNail (SEPA plus econazole), an investigational antifungal lacquer for the treatment of onychomycosis, a common fungal infection of the nail. Trial data indicate that the study met its primary safety and pharmacokinetic endpoints, with no serious drug-related adverse events and no detectable systemic absorption. The randomized, double-blind, placebo controlled trial enrolled 18 patients suffering from onychomycosis across 2 clinical sites in the US. Subjects received twice daily applications of either EcoNail or placebo lacquer 6 weeks, and were monitored for adverse events and systemic absorption. An ongoing open-label extension is currently underway, with all patients receiving EcoNail once daily to all nails for an additional 12 weeks, and MacroChem announced plans to initiate a preliminary efficacy trial in early 2005.

PowderMed has issued results of their first phase I trial of their DNA influenza vaccine candidate. Results indicate that the trial met its primary endpoints, with all trial doses of the drug being well tolerated and a significant number of subjects exhibiting immune response sufficient to meet standards established for European approval after 56 days. Furthermore, the highest dose of the drug met the criteria after just 21 days, and 100% of subjects receiving this dose achieved seroprotective antibody levels. This open-label trial enrolled 36 healthy adult volunteers, who were randomized to receive one of three single doses of the vaccine (1, 2 and 4 micrograms), followed by a 56 day follow-up observation.

The Immune Response Corporation presented data from their ongoing phase II study of Remune, their investigational antiretroviral vaccine for the treatment of HIV, at the 7th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland. Preliminary results from the 37 subjects having thus far received treatment demonstrate positive trends in several immune-response indicators, including stabilization of total CD4+ T-cell counts, increased HIV-specific CD8+ memory T-cells, and decreased levels of activated CD38+ T-cells, following treatment. This multi-center, single-blind study has to date randomized 37 of a projected 51 treatment naïve HIV-positive subjects to receive one of two treatment regimens of Remune (one injection Remune & two placebo or three injections Remune), or Incomplete Freund's Adjuvant (a non-targeted immunostimulatory) or placebo over 28 weeks; the four arms of the study each received injections at trial initiation and weeks 12 and 24. Immune Response, following these results, has announced plans for a rollover study which will include treatment with both Remune and IR103, another of the company’s investigational antiretroviral drugs.

October 4, 2004

LAB International has announced positive results of a phase I/II trial of their Growth Hormone Releasing Hormone (GHRH) analog, being developed as an inhalable treatment for growth hormone (GH) deficiency caused by a number of diseases, including HIV, chronic renal failure and lipodystrophy. The drug was found to be safe and well tolerated, with no significant adverse events. Furthermore, the drug produced significant increases in serum GH levels up to 12 hours after treatment at all dosing regimens, and demonstrated a higher-than-expected efficacy for this endpoint. No impact on normal nocturnal GH secretion was observed. The placebo-controlled, single-dose safety and efficacy cross-over study enrolled a total of 10 healthy volunteers, all of whom received randomized sequential dosing regimens of 5-25 ug/kg and placebo. LAB announced plans for both indication-driven phase II trials and another phase I/II dose-ranging trial to establish minimum therapeutic dose.

September 20, 2004

The Immune Response Corporation issued positive interim results of their investigational HIV therapy Remune. 12-week data obtained thus far from the ongoing study indicate that the drug possesses potential anti-HIV immunogenic properties in treatment-naïve patients: subjects receiving Remune showed significant increases in HIV-specific CD-4+ and CD-8+ memory T-cells, compared with subjects receiving Incomplete Freund’s Adjuvant (IFA) or saline. No significant changes were seen in CD4 cell count or viral load. The multi-center, single-blind, randomized study enrolled a total of 50 HIV-positive, treatment naïve subjects for 28 weeks, who were to receive either one or three treatments with Remune, or three treatments of IFA or saline. All subjects have been treated at least through week 12, and 30 subjects to date have completed the full 28 week treatment course.

August 2, 2004

Viral Genetics reported preliminary results of a clinical study of their drug VGV-1, an immune modulator for the treatment of HIV infection. Results indicated that the drug significantly improved disease state, with a 75% decrease in viral load after a 270 day treatment-free observation period that followed dosing; 28% of subjects achieved a drop of greater than 90%. This prospective, masked, non-randomized single center study enrolled treatment-naïve subjects in China, who received weekly intramuscular injections of the drug bi-weekly for 8 weeks. No additional HIV therapy was administered during the dosing regimen or the 270 day observation period that followed. Viral Genetics is now planning a phase III study in South Africa.

July 19, 2004

Incyte reported the final results of a phase IIa study of Reverset, a nucleoside-analog reverse transcriptase inhibitor (NRTI), at the 15th International AIDS Conference in Bangkok. Trial data indicated that adding Reverset to standard retroviral therapy improved disease symptoms in HIV, producing a statistically significant mean reduction in viral load of 0.8 log10 copies/ml following 10 days of treatment. Furthermore, the magnitude of viral load reduction was found to be dose dependent, and treatment with Reverset produced no new resistance mutations. The open label study enrolled a total of 30 treatment naïve and 10 treatment experienced subjects, who received one of three daily doses of Reverset (50, 100 or 200 mg/day) in addition to their standard therapy; among the highest dosing cohort, 87.5% of treatment naïve and 50% of treatment experienced subjects achieved viral loads below 400 copies/ml. The drug was well tolerated, with the most common adverse events being cold-symptoms, headache and fatigue. Incyte announced that a follow-up study is currently enrolling subjects in the US, Germany and France.

April 19, 2004

Theratechnologies reported positive results from a phase II trial investigating ThGRF, a growth hormone-releasing factor analogue for the treatment of HIV-associated lipodystrophy. Results demonstrated a statistically significant treatment effect in the total cholesterol to HDL cholesterol ratio at week 12. Data demonstrated an average decrease of 0.34 in the 2-mg group compared to an average increase of 0.21 in the placebo group. Results also showed good glycemic control, including in glucose-intolerant and diabetic patients. The double-blind, randomized, placebo-controlled study enrolled 61 subjects at seven sites in the U.S. and Canada. Subjects received a subcutaneous injection of 1 mg, 2 mg or placebo, daily over 12 weeks. Based on these positive results, the company is planning to further develop this drug in phase III testing.

March 1, 2004

Gilead Sciences reported positive preliminary results from a phase III trial investigating Viread (tenofovir disoproxil fumarate), a nucleotide analogue reverse transcriptase inhibitor for the treatment of HIV. Data demonstrated that 73% and 69% of subjects showed a reduction of viral load to less than 50 copies/mL. Results showed that treatment with stavudine was associated with greater elevations in fasting triglyceride and cholesterol levels and a higher incidence of investigator-defined lipodystrophy compared to treatment with Viread. The three-year, international, double-blind randomized, (called Study 903) enrolled 600 antiretroviral-naive subjects. Subjects received Viread, lamivudine and efavirenz or stavudine, lamivudine and efavirenz over 144 weeks. The most common adverse events observed were viral infection, diarrhea and headache, and each occurred with similar frequency in the two study arms.

February 16, 2004

Bristol-Myers Squibb reported results from a phase IIa trial investigating BMS-488043, an HIV-1 attachment inhibitor for the treatment of HIV infection. Results demonstrated antiviral activity in HIV-1 infected patients, achieving proof of concept for BMS-488043. Data showed most subjects in both treatment arms experienced at least a 1.0 log10 copies/mL decline in viral load, some achieving reductions of up to 2.0 log10 copies/mL. Moderate adverse events reported were fatigue, abscess, and diarrhea. The placebo-controlled study (called AI430-003) enrolled 30 HIV-1 infected subjects who did not have a medical indication for antiretroviral therapy, had a CD4 cell count of greater than 250 cells/mm3, and a plasma viral load of 5,000 to 500,000 copies/mL. Subjects received BMS-488043 (800 or 1800 mg) or placebo every 12 hours for seven days. Results were reported at the 11th Conference on Retroviruses and Opportunistic Infections in San Francisco.

Pharmasset and Incyte reported preliminary results from an ongoing phase II trial investigating Reverset, a nucleoside analog that targets HIV-1 reverse transcriptase enzyme. Results demonstrated a reduction in viral load of more than 1.7 log (10) after 10 days of monotherapy treatment. Data showed plasma pharmacokinetic values were linear with dose on days 1 and 10. Mean viral load decline for the three dose levels were 1.67 (+/- 0.24) log (10) at 50 mg, 1.74 (+/- 0.32) log (10) at 100 mg, and 1.77 (+/- 0.23) log(10) at 200 mg, with maximum decreases ranging from 1.2 to 2.3 log(10). The randomized, double-blind, dose escalation study enroll 30 subjects with HIV infection. Subjects were given Reverset (50, 100, or 200 mg) or placebo, once a day for 10 days. Results were reported at the 11th Conference on Retroviruses and Opportunistic Infections in San Francisco.

Tanox reported results from a phase Ib trial investigating TNX-355, a monoclonal antibody for the treatment of HIV-1 infection. Results showed reductions from baseline of 0.5-1.7 log10 in HIV-1 RNA levels observed in 21 out of 22 subjects. Mean peak decreases from baseline in log10 viral loads of 0.99, 1.11 and 0.96 occurred by week two in the three arms of the trial, respectively. The randomized, multi-dose study enrolled 22 HIV-1 infected subjects who were placed in two treatment groups to receive TNX-355 intravenously as an infusion either weekly or every two weeks for nine weeks. The two arms had dosing of 10mg/kg/weekly and 6mg/kg/every two weeks after a 10mg/kg initial dose. Results were reported at the 11th Conference on Retroviruses and Opportunistic Infections in San Francisco.

January 26, 2004

GlaxoSmithKline reported positive final analysis from an earlier phase III trial investigating Lexiva (fosamprenavir, GW433908 (908)), a protease inhibitor approved for HIV infection in October 2003. Results showed that 66% of subjects on Lexiva achieved viral load < 400 copies/mL, compared to 51% of subjects taking nelfinavir. In Addition, 55 % of subjects taking Lexiva achieved a viral load < 50 copies/mL, compared to 41% (n=34) of subjects on nelfinavir. The 48-week, open-label, randomized, multi-center study, called NEAT, evaluated the safety and efficacy of Lexiva compared to nelfinavir (NFV/Viracept) in antiretroviral therapy-naive subjects with HIV. Subjects were randomized to receive either 1400mg of Lexiva twice daily or 1250mg of nelfinavir. Results were reported in the January issue of The Journal of Acquired Immune Deficiency Syndrome (JAIDS).

November 3, 2003

Roche and Trimeris reported positive results from a phase IV trial investigating Fuzeon (enfuvirtide), a fusion inhibitor approved for the treatment of HIV-1 infection. Results showed that Fuzeon, in combination with other anti-HIV drugs, provides a substantial virologic and immunologic benefit through 48 weeks. Data showed that subjects with a viral load greater than 100,000 copies, per mL of blood, were more than three times as likely to achieve undetectable levels of HIV with Fuzeon compared with a regimen without it (15% vs. 4%). In addition, subjects taking a Fuzeon-based regimen experienced twice the immune cell increase as those without it. The international, 48-week, subgroup analyses of the TORO 1 and TORO 2 studies enrolled 1,000 subjects with advanced HIV. Results were reported at the 9th European AIDS Conference (EACS).

August 11, 2003

Vertex Pharmaceuticals and GlaxoSmithKline reported positive preliminary results from a phase III trial investigating 433908 (908), a protease inhibitor for the treatment of HIV. Results demonstrated that 908 exhibited antiviral activity in treatment-experienced patients. The study assess a once daily (QD) or twice daily (BID) dosing of 908 boosted with ritonavir compared to a third treatment arm with Lopinavir/ritonavir (LPV/r) BID, all in combination with two nucleoside reverse transcriptase inhibitors. Subjects with viral load below 400 copies/mL, 908/r BID (58%) and LPV/r BID (61%) demonstrated comparable levels of antiviral activity. The proportion of subjects who achieved vRNA below 50 copies/mL at 48 weeks was also similar in the 908/r BID (46%) and LPV/r BID (50%) arms. The open-label study, called CONTEXT, enrolled 320 treatment-experienced subjects with prior virologic failure and was designed to assess antiviral efficacy and safety of the three study regimens at 24 and 48 weeks.

August 4, 2003

Elan reported negative results from a phase III trial of Antegren (natalizumab), a monoclonal antibody for the treatment of Crohn’s disease. Results showed that the drug did not meet the primary endpoint of response, as defined by a 70-point decrease in the Crohn's Disease Activity Index (CDAI) at week 10. Data did demonstrate however, that the time to remission and mean changes in CDAI were significantly improved with natalizumab compared with placebo. Remission was defined as a CDAI score of less than or equal to 150 at week 10. The overall rates of side effects between natalizumab and placebo treatment groups were similar throughout the study. The most common adverse events seen in the trial were headache, nausea and abdominal pain across both groups. The double blind, randomized, placebo-controlled trial, called ENACT-1 (Evaluation of Natalizumab in Active Crohn's disease Therapy-1) enrolled 905 subjects.

The BioBalance Corp. reported positive results from a clinical study investigating Probactrix, a competitor E. coli containing agent for the treatment of diarrhea and other symptoms associated with HIV infection. Results showed that Probactrix significantly reduced gastrointestinal complaints in as early as three to five days after dosing. Data also demonstrated diarrhea symptoms were markedly reduced or disappeared in the treatment arm, compared with the control group. In the treatment arm, there was significant improvement noted in bowel movement frequency during therapy, and one month after stopping administration of the drug. The drug was well tolerated with no reported side effects. The controlled study enrolled 50 subjects undergoing a standard course of HIV therapy at the Moscow Center of HIV.

June 30, 2003

Hollis-Eden Pharmaceuticals reported positive results from a phase II trial investigating Immunitin (HE2000) for the treatment of opportunistic infections in subjects with AIDS. Results showed subject receiving Immunitin experienced a statistically significant reduction in the total number of all opportunistic infections compared with subjects receiving placebo. Subjects in the placebo group experienced 67% more opportunistic infections than those treated with Immunitin. Immunitin treated subjects experienced a statistical trend towards reduced circulating C - reactive protein (CRP) compared to placebo treated patients. The 25 evaluable subjects in the study were dosed once a day with either Immunitin or placebo for 5 days and then observed for 5 weeks before receiving and additional 5-day treatment course. Results were reported at the National Foundation for Infectious Diseases Conference on Antimicrobial Resistance, in Bethesda, Maryland.

SciClone Pharmaceuticals reported positive results from a phase III trial in Japan investigating Zadaxin, a synthetic thymosin alpha 1 for the treatment of hepatitis B. Results showed that 29% of subjects (1.6 mg group) had negative hepatitis B viral DNA, 23% of subjects demonstrated a successful interruption of viral replication and 22% of subjects demonstrated a sustained seroconversion of the hepatitis B e-antigen. Subjects in the .8 mg dose group demonstrated similar results. Subjects received Zadaxin at either a 1.6 or .8 mg dose twice a week for six months and were observed for up to one year after treatment. The 18-month study enrolled 283 subjects. The safety profile was excellent without significant drug related side effects or toxicities.

May 5, 2003

Boehringer Ingelheim reported positive results from a post-marketing study comparing Viramune (nevirapine) to Sustiva (efavirenz) in the treatment of HIV-1 infection. Results demonstrated the efficacy of Viramune was comparable to efavirenz in HIV treatment. Data showed a viral load of less than 50 copies was reached by 70% of the subjects in the Viramune once-daily arm, 65.4% in the Viramune twice-daily arm, 70% in the efavirenz arm and 62.7% in the Viramune + efavirenz arm. The Viramune + efavirenz arm was statistically inferior to the efavirenz alone arm due to decreased tolerability, resulting in more drug discontinuations. The randomized, prospective, multi-center study enrolled 1,216 subjects in 17 countries. All treatment arms also included the nucleoside analogue drugs stavudine and lamivudine.

March 4, 2003

Microscience reported positive results from a phase I trial investigating Micro-TY, their oral typhoid vaccine. Results show the vaccine was safe, well tolerated, and highly immunogenic. Subjects who received the highest dose levels of treatment experienced an excellent immune response, measured by mucosal and systemic responses. The incidence of adverse events was similar to those found in the placebo group. No bacteraemias attributable to the treatment was found. The randomized, double blind, multi-center, placebo-controlled, study enrolled 60 healthy adult subjects. The live attenuated vaccine was administered in a new oral, low dose, freeze-dried formulation.

VaxGen reported negative results from a phase III trial investigating AIDSVAX (rgp120) for the prevention of HIV infection. Results showed the vaccine did not demonstrate a significantly significant reduction of HIV infection within the study group as a whole. The reduction of infection among all subjects treated with the vaccine was 3.8% compared to placebo. Data pertaining to certain racial subgroups seem to indicate a positive efficacy trend. There were 67% fewer HIV infections among ethnic minorities and 78% fewer HIV infections among black subjects compared to placebo. Further data analysis is needed to confirm these results. The randomized, double blind, placebo-controlled study enrolled 5,417 subjects deemed at higher risk for HIV infection. Subjects were administered seven vaccinations via injection during the 36-month trial. The trial was conducted in the U.S., Canada, Puerto Rico, and the Netherlands. VaxGen is continuing testing on the vaccine for other HIV subtypes and in alternative formulations.

February 24, 2003

Gilead Sciences reported positive results from a phase III trial comparing Viread (tenofovir disoproxil fumarate), a nucleotide analogue reverse transcriptase inhibitor to stavudine for the treatment of HIV infection. Results showed that subjects who received Viread experienced less lipodystrophy, lower elevations in fasting cholesterol and triglyceride levels, and similar reductions in viral load compared to stavudine. Data revealed that 82% of subjects treated with Viread achieved an HIV RNA reduction of less than 400 copies/ml compared to 78% of subjects treated with stavudine. Study 903 is an ongoing, randomized, double blind trial designed to compare the efficacy and safety of Viread plus lamivudine/efavirenz to stavudine plus lamivudine/efavirenz in 600 antiretroviral-naïve subjects with HIV infection.

Vertex Pharmaceuticals reported positive results from two-phase III trials investigating GW433908 (908), a protease inhibitor for the treatment of HIV/AIDS. In the NEAT trial, results showed that 66% of 166 subjects achieved an undetectable viral load (vRNA) with 908 compared to 51% of 83 subjects who received the alternative treatment nelfinavir. Data showed that 28% of subjects who received nelfinavir were considered virologic failures compared to 14% of subjects with 908. In addition, 55% of subjects in the 908 group achieved a viral load less than 50 copies/ml compared to 41% of subjects in the nelfinavir group. The open-label, randomized, multi-center study called NEAT enrolled 249 HIV-positive subjects. Subjects were treated with either 1400 mg 908 or 1250 mg of nelfinavir twice daily for 48 weeks. Positive preliminary results were also reported from the CONTEXT trial comparing 908 plus Ritonavir to Lopinavir plus Ritonavir in 320 treatment-experienced subjects.

October 7, 2002

Triangle Pharmaceuticals reported positive results from a phase III trial comparing Coviracil and Zerit. The study involved 571 subject in the US, Europe, Mexico and South America. Subjects were administered once-a-day Coviracil or Zerit twice daily combined with a background regimen of once-daily Sustiva and Videx EC. At 52 weeks, Coviracil subjects produced better antiviral activity (virologic failure rate) at 4.7% compared to Zerit subjects at 14.1%. Coviracil also produced a significantly better immunologic response with a mean CD4+ increase of 152 cells/mm3 as compared to an increase of 117 cells/mm3 in the Zerit group. 81% of Coviracil subjects had undetectable viral loads compared to 70% of Zerit subjects. Additionally, Coviracil was better tolerated in subjects than Zerit (6.7% versus 13.9%).

August 5, 2002

In an open-label, prospective, randomized, controlled phase IIb clinical trial, the safety and biological effects of Ampligen, an immunotherapeutic by Hemispherx Biopharma, were evaluated in subjects with drug-resistant HIV infection. The control group received the HAART regimen alone, and the group treated with the investigational drug received Ampligen in addition to the HAART regimen. Results showed that after a median duration of 4.5 months, the Ampligen group experienced a mean HIV-1 viral load decrease of 0.50 log using the Roche Amplicor assay.

May 28, 2002

Positive results were reported from a second phase III trial (TORO 2) of Trimeris and Hoffmann-La Roche's T-20 for the treatment of HIV infection. Results demonstrated that T-20 administered in combination with an optimized anti-retroviral treatment regimen provides a significant additional decrease in virus level compared to an anti-retroviral treatment regimen alone. At 24 weeks, subjects who received T-20 achieved a mean reduction in HIV levels of 1.43 log10 copies/mL, compared to a mean reduction of 0.65 log10 copies/mL for those in the control arm. The difference in the magnitude of the decrease between the two arms (the primary endpoint) was statistically significant at 0.78 log10 copies/mL.

March 11, 2002

Phase IIa trial results indicate that TMC125 produces antiviral activity in HIV subjects infected with NNRTI-resistant virus and failing NNRTI therapy. In this open-label trial, 16 subjects received TMC125 for one week. The median reduction in viral load was 87% after seven days of treatment, with viral load reductions ranging from 37% to 98%. No genotypic or phenotypic evidence of the development of resistance was observed during the trial. TMC125 is being developed by Tibotec-Virco.

Phase III trial results suggest that a one-capsule, once-daily extended release formulation of Bristol-Myers Squibbs Zerit (stavudine) has similar virologic activity to the approved immediate release formulation. The multinational, double-blind, placebo-controlled trial evaluated treatment in antiretroviral nave HIV positive subjects. The trial was designed to compare Zerit extended release to Zerit immediate release when used in combination with Sustiva (efavirenz) and Epivir (3TC). Data showed that 80% of subjects receiving Zerit extended release achieved viral load suppression below 400 copies/mL after 24 weeks of treatment, compared to 82% in the Zerit immediate release arm. Additionally, 55% in each arm achieved a viral load of less than 50 copies/mL.

February 25, 2002

Forty-eight week phase II trial results indicate that the addition of T-20 to a standard antiretroviral regimen produces greater decreases in plasma viral load than treatment with the antiretroviral control regimen alone. The randomized trial evaluated three doses of T-20 in combination with a regimen of oral antiretrovirals. Data showed that 55% of subjects in the combined T-20 arms achieved undetectable HIV-RNA levels of less than 400 copies/mL, and 47% achieved levels of less than 50 copies/mL. Additionally, CD4+ cell count increases were higher in subjects receiving T-20 regimens (132 cells/mu1) versus the control group (90 cells/mu1). T-20 is being developed by Trimeris and Hoffmann-La Roche.

January 14, 2002

Positive results were reported from a phase I trial of ACH-126,443 (beta-L-Fd4C), an L-nucleoside analog with in vitro activity against chronic hepatitis B and human immunodeficiency virus. The trial was designed to evaluate six dose levels of the drug in healthy subjects. Pharmacokinetic results demonstrated ideal absorption of the compound into the bloodstream, and the data supports once daily dosing. ACH-126,443 is being developed by Achillion Pharmaceuticals.

Statistically significant preliminary results were reported from an ongoing phase III trial of Corixa's RC-529 synthetic adjuvant in combination with Rhein Biotech's hepatitis B vaccine. The trial was designed to compare vaccination with the hepatitis B vaccine plus the RC-529 adjuvant to vaccination with the vaccine alone in healthy adults who were not immune to hepatitis B virus (HBV). A total of 285 subjects received at least one vaccination, and 272 of these subjects were evaluated for efficacy. Results showed that there were significantly more subjects seroprotected after two immunizations with the hepatitis B vaccine plus RC-529 than with the vaccine alone (95.5% versus 82.1%). Analysis of secondary efficacy endpoints, such as seroconversion rates at days 30 and 60, also showed a statistically significant benefit in favor of the RC-529/vaccine combination.

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