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Genentech and Biogen reported negative results from a phase II/III trial of Rituxan for the treatment of systemic lupus erythematosus (SLE). This randomized, double-blind, placebo-controlled, multi-center study enrolled 257 subjects with moderate-to-severe SLE on a background immunosuppressant, in the US and Canada. The subjects received Rituxan plus prednisone or placebo plus prednisone in two infusions fifteen days apart. They were retreated six months later with the same regimen. Efficacy was evaluated every four weeks for fifty-two weeks. The primary endpoint, the proportion of subjects who achieved either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) using the British Isles Lupus Assessment Group (BILAG) index compared to placebo at fifty-two weeks, was not reached. The study also did not meet any of the secondary endpoints, including time adjusted area-under-the-curve minus baseline of BILAG score over fifty-two weeks; proportion of subjects who achieve BILAG C or better in all domains at Week twenty-four; time to moderate or severe flare over 52 weeks; change in SLE Expanded Health Survey physical function score from baseline at Week fifty-two; and proportion of subjects who achieve a MCR with 10 mg prednisone per day from Weeks 24 to 52. A phase III trial of Rituxan evaluating lupus nephritis is currently underway and results are expected in Q1 of 2009.
Immunomedics reported positive results from a follow-up phase I/II trial of epratuzumab for the treatment of systemic lupus erythematosus (SLE). Phase I of the trial enrolled 12 subjects with SLE and analyzed the effect of epratuzumab on circulatory B-cell subsets. Results showed that epratuzumab preferentially targets naive and transitional B-cells. Phase II of the trial enrolled 11 subjects with SLE and 7 subjects without SLE. It was designed to analyze the effect of epratuzumab on the inhibition of the activation of B-cells. Epratuzumab stopped the over-activation of B-cells from SLE subjects but not normal B-cells, when activated by certain immune stimulating agents. Based on the results, Immunomedics plans to move forward with the development of epratuzumab.
ViroPharma and Wyeth announced negative results from a phase II trial of HCV-796 for the treatment of hepatitis C. This randomized, open-label trial placed subjects into one of three treatment groups: Group 1 was made up of treatment naive subjects who were to receive pegylated interferon and ribavirin (control therapy); Group 2 was made up of treatment naive subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours and Group 3 was made up of non-responding subjects who were to receive pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours. Primary outcomes included antiviral activity, the percentage of subjects with undetectable plasma HCV RNA levels at weeks 4, 12, 24, and 48 and the percentage of subjects with undetectable sustained virologic response (SVR). Interim safety data review showed elevated liver enzyme levels in 8% of HCV-796-treated subjects leading to the withdrawal of two subjects, compared with 1% in pegylated interferon plus ribavirin-treated subjects. Interim efficacy data showed that at weeks 4 and 12, 45% and 73% of treatment-naive HCV-796 plus pegylated interferon and ribavirin-treated subjects had undetectable HCV levels, compared with 7% and 39% of treatment-naive pegylated interferon and ribavirin-treated subjects, respectively. At total of 4% and 23% of HCV-796 plus pegylated interferon and ribavirin-treated subjects, previously unresponsive to treatment, had undetectable HCV levels at weeks 4 and 12, respectively. However, based on the negative safety data, ViroPharma and Wyeth discontinued the dosing of subjects enrolled in the trial.
Aspreva and Roche issued negative results from a phase III trial of CellCept for the treatment of lupus nephritis. This two-phase induction to maintenance study enrolled 370 subjects. It was designed as a randomized open label comparison of CellCept to intravenous cyclophosphamide (IVC) for the first six months (induction phase), followed by a double-blind comparison of CellCept to azathioprine for up to three years (maintenance phase). Treatment response in the induction phase was defined as a decrease in proteinuria and the stabilization or improvement of serum creatinine. Although response rates were similar between the two groups, the trial did not meet the primary endpoint of demonstrating that CellCept is superior to IVC in inducing treatment response. The response rate was 56.2% in the CellCept arm and 53% in the IVC arm. Treatment was well tolerated, with adverse events similar between the two arms. The maintenance phase of the trial is ongoing. Roche and Aspreva plan to further evaluate the data to determine the potential for a regulatory submission.
Gilead released positive results from a phase III trial of Viread for the treatment of "e" antigen (HBeAg)-positive chronic hepatitis B. This multi-center double-blind study, dubbed 103, enrolled 266 subjects who were randomized in a 2:1 ratio to receive either Viread (300 mg once daily) or Hepsera (10 mg once daily). The trial was designed to establish the non-inferiority of Viread to Hespera. The primary endpoint was the proportion of subjects with a complete response at week 48, defined by serum hepatitis B (HBV) DNA levels below 400 copies/mL and histologic improvement. This endpoint was achieved; 66.5% of subjects in the Viread arm had a complete response compared to 12.2% in the Hepsera arm (p less than 0.001), thus confirming non-inferiority. Adverse events were comparable between the two treatment arms. Based on the results, Gilead plans to file a NDA with the FDA and a MAA with the EMEA in the fourth quarter of 2007.