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AIDS and AIDS related infections

March 24, 2014

Merck reported results of a 96-week, openlabel study of ISENTRESS (raltegravir) for the treatment of AIDS. The 1,809-patient study compared ISENTRESS to protease inhibitorbased treatment regimens in a treatment-naïve population. Patients were randomized to receive atazanavir/r (300mg/100mg once daily), ISENTRESS (400mg twice daily) or darunavir/r (800mg once daily). All patients also received emtricitabine/tenofovir disoproxil fumarate (200/300mg once daily). The study reported 92% of patients completed the 96-week study. Equivalent rates of virologic control were attained for all regimens. The percentage of patients maintaining ≤50 copies/mL at week 96 was 94%, 88% and 89% for ISENTRESS, atazanavir/r and darunavir/r, respectively, based on intent-to-treat analysis. One percent, 16% and 5% discontinued ISENTRESS, atazanavir/r and darunavir/r, respectively, for toxicity largely due to clinical jaundice and hyperbilirubinemia with atazanavir/r, and gastrointestinal symptoms with both atazanavir/r and darunavir/r. In this composite analysis, atazanavir/r was inferior to both ISENTRESS by 15% (97.5% CI: 10%, 20%) and darunavir/r by 7.6% (97.5% CI: 2.3%, 13%). Darunavir/r was inferior to ISENTRESS by 7.5% (97.5% CI: 3.2%, 12%).

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.

February 12, 2007

GeoVax issued positive preliminary results from two ongoing phase I trials of their DNA/MVA AIDS vaccine. The first trial enrolled 11 subjects, 9 of whom received the vaccine and 2 of whom received placebo. The subjects received 1/10 of the vaccine administered at week 0 and week 8 to prime the immune response which was boosted by the administration of another 1/10th dose of the vaccine at week 16 and again at week 24. Results revealed a good safety profile and positive immune response. The second trial has enrolled 36 subjects, 30 of whom received the vaccine at the full dose and six of whom received placebo. Preliminary results have shown an acceptable safety profile. Complete results are expected later in 2007. Pending positive results, a large scale phase II trial is planned for late 2007 or early 2008.

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.

January 31, 2005

Advanced Viral Research announced final results of a phase I/II trial of their investigational immunomodulatory biopolymer AVR118, for the treatment of anorexia/cachexia related to AIDS, at the 2005 Annual Assembly of the AAHPM/HPNA. Trial results indicated that the drug was efficacious in treating primary symptoms of anorexia/cachexia, with improvements from baseline in body weight, strength, BMI, and calf circumference. The degree of improvement was generally dose related. Efficacy was also observed in secondary endpoints, including voluntary reporting improvements in mood, fatigue, activity levels, and other quality of life measurements; these reports were more common at higher doses. The drug’s favorable safety profile was also reconfirmed, with no drug related adverse events and no dose-dependent adverse event profile established. This open-label, dose-ranging study enrolled 30 subjects at a single site in Israel; all subjects were randomized to receive one of 3 regimens of subcutaneous AVR118 (0.4, 2.0 or 4.0 ml 6 days per week for 4 weeks).

ID Biomedical has issued positive results of a phase II study of StreptAvax, their subunit protein-based vaccine under investigation for the treatment and prevention of group A Streptococcal diseases. Study data indicated immunogenic potential, with to cohort of subjects receiving the vaccine demonstrating significant increases in levels of serum antibodies against all 27 of the vaccines immunogenic components (26 M protein serotypes and the Spa protein; p<0.0001). Individual subjects responded, on average, to 25 of the 27 peptides, with each peptide producing response in 87% of subjects. This international, open-label study enrolled 90 healthy adult subjects; 70 were randomized to receive StreptAvax, and 20 received an approved hepatitis A vaccine, to serve as a comparator for immune response magnitude. Full safety data for this trial was expected by the end of Q1 2005, ahead of a pre-IND meeting with the FDA to discuss pediatric testing later this year.

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.

July 5, 2004

Immtech International reported positive preliminary results of their phase II trial investigating DB289, for the treatment of Pneumocystis carinii pneumonia (PCP) in AIDS patients. Data from the first cohort of subjects have indicated that investigational doses of the drug have been safe and efficacious in treating PCP infection. The first cohort in this open label study received a pilot dosing regimen of 50 mg of DB289 twice daily for 21 days. A second study cohort is currently being treated with a 100 mg twice-daily regimen of the drug, and preliminary data from this group show a dose dependent improvement in efficacy and a reduction in time to return to normal lung function over the pilot group. The study is being conducted is being conducted in PCP-treatment-refractory AIDS patients in Peru.

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).

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.

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.