Clinical Trials

Lupus Drug Successful in Second Pivotal Trial

The second of 2 large-scale, double-blind, placebo-controlled, multicenter phase 3 clinical trials of belimumab (Benlysta), involving seropositive patients with systemic lupus erythematosus (SLE), returned positive results. Researchers from BLISS-76, the second of the 2 studies, announced the positive results on November 2. Both clinical trials met their primary end points, and BLISS-76 study results through 52 weeks showed that belimumab 10 mg/ kg plus standard of care was superior to that of placebo plus standard of care. Belimumab 10 mg/kg plus standard of care achieved a statistically significant improvement in patient response rate as measured by the SLE Responder Index at week 52, compared with placebo plus standard of care—43.2% for 10 mg/kg belimumab, 40.6% for 1 mg/ kg belimumab, and 33.8% for placebo.

If approved by the FDA, belimumab would be the first drug ever developed and approved specifically for the treatment of lupus.

Encouraging Results from 2 Trials for Hep B Drug

Two phase 3 clinical trials recently showed positive results concerning the safety and efficacy of once-daily tenofovir disoproxil fumarate (Viread) among adult patients with chronic hepatitis B virus (HBV) infection.

Studies 102 and 103 were multicenter, randomized, double-blind phase 3 clinical trials. The new data show that most of the patients receiving treatment with tenofovir disoproxil fumarate for up to 144 weeks experienced sustained suppression of HBV DNA levels in the blood to below 400 copies/mL (87% in Study 102 and 71% in Study 103). Additionally, 8% of all patients in Study 103 (HBeAg-positive) experienced “s” antigen (HBsAg) loss, which can contribute to resolution of chronic HBV infection. Interestingly, no resistance to tenofovir disoproxil fumarate developed among patients who received the drug for up to 3 years.

Phase 3 Results Positive for ED Treatment Avanafil

The recent results of REVIVE (TA-301), a phase 3 pivotal study evaluating the safety and efficacy of avanafil, an investigational drug candidate for the treatment of erectile dysfunction (ED), met all primary end points. The study demonstrated statistically significant improvement in erectile function as measured by the Sexual Encounter Profile (SEP) and improvements in the International Index of Erectile Function (IIEF) score. In addition, the study demonstrated successful intercourse in 30 minutes or less and a favorable side effect and safety profile. The REVIVE study, a randomized, placebo-controlled, phase 3 study, enrolled 646 men with a history of generalized ED for at least 6 years. Patients underwent a 4-week, nontreatment run-in period followed by 12 weeks of treatment with either 50, 100, or 200 mg avanafil or placebo. All FDA-defined primary end points—including improvement in erectile function as measured by the SEP and improvements in the IIEF score—were met across all 3 doses of avanafil. Also, full efficacy was reported by patients in 30 minutes or less and was maintained for all doses across multiple time points from 30 minutes to beyond 6 hours.

Cholesterol Drug Shows Lowering of LDL and Positive Safety Profile

Results from an ongoing phase 3 clinical trial involving the cholesterol management compound lomitapide (AEGR-733)—a microsomal triglyceride transfer protein inhibitor small molecule drug—have shown that the drug significantly reduces patients’ low-density lipoprotein (LDL) cholesterol versus baseline and that it is well-tolerated and exhibits a promising safety profile.

The phase 3 trial, which currently includes 22 patients, is evaluating the long-term efficacy, safety, and tolerability of lomitapide for the treatment of patients with homozygous familial hypercholesterolemia (HoFH), a rare and extremely serious condition causing severely elevated levels of LDL cholesterol, which results in life-threatening cardiovascular events. Patients with HoFH face a shortened life expectancy and limited treatment options.

When the most recent data analysis took place, 14 of the patients had been involved in the trial and taking lomitapride for a minimum of 26 weeks, and 7 had been treated with lomitapride for 56 weeks. The group of 14 patients on the 26-week lomitapride treatment had a mean reduction in LDL cholesterol of 49% on top of maximum tolerated background therapy. Average baseline LDL cholesterol levels were 351 mg/dL, and 6 of the 14 patients achieved an LDL cholesterol level below 100 mg/dL, with 10 of the 14 achieving LDL cholesterol levels below 165 mg/dL.

In addition, lomitapride continues to demonstrate a positive safety and tolerability profile. Modestly increased hepatic fat levels at 26 weeks were reduced by week 56.

The results were presented at the American Heart Association’s “Scientific Sessions 2009” on November 16.