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Idiopathic Thrombocytopenic Purpura (ITP)
February 11, 2008
Achillion released positive twenty-four week results from a phase II trial of elvucitabine for the treatment of HIV. This randomized, double-blind study enrolled seventy eight treatment-nave subjects with wild-type HIV-1 virus. The subjects received 10 mg/day elvucitabine with 600 mg/day efavirenz and 300 mg/day tenofovir or 300 mg/day 3TC with 600 mg/day efavirenz and 300 mg/day tenofovir. The study included a twelve-week blinded treatment period after which responders (subjects with viral loads below 400 copies/mL, or less than 2 log10 decrease) continued to an ongoing eighty four-week open-label extension period. Elvucitabine had a potent anti-viral effect similar to 3TC, with a mean change in HIV-RNA from base-line in the elvucitabine treatment group of -3.0 log10 (+/- 0.6) versus -3.2 log10 (+/- 0.5) in the 3TC treatment group. In the elvucitabine-treated group, 96% of subjects reached undetectable viral load, defined as achieving fewer than 50 copies/ml after twenty four weeks of therapy, compared to 94% in the 3TC-treated group. Elvucitabine was well-tolerated and demonstrated a safety profile comparable to 3TC for both incidence and severity adverse events. Analysis of forty-eight and ninety-six week data are currently under evaluation.
Amgen issued positive pooled results from two phase III trials of Nplate for the treatment of Idiopathic Thrombocytopenic Purpura (ITP). These parallel phase III trials enrolled sixty three splenectomized subjects and sixty two non-splenectomized subjects with ITP and a mean of three platelet counts of 30,000 per microliter or less. The subjects were randomized to subcutaneous injections of Nplate (n=42 in splenectomized study and n=41 in non-splenectomized study) or placebo (n=21 in both studies). The primary endpoint was efficacy as measured by a durable platelet response and treatment safety. Durable response was defined as a platelet count above 50,000 per microliter during six or more of the last eight weeks of treatment without rescue therapy ever being administered. The durable platelet response rate was significantly greater in subjects treated with Nplate compared to those in the placebo group in both studies (difference in proportion of splenectomized subjects responding 38% (95% CI (23.4-52.8 percent); p less than 0.0001); difference in proportion of non-splenectomized subjects responding 56% (95% CI (38.7-73.7 percent); p less than 0.0001)). The overall platelet response was 88% in non-splenectomized subjects compared to 14% in the placebo group; and 79% in splenectomized subjects given Nplate compared to no splenectomized subjects given placebo (p less than 0.0001). Nplate-treated subjects achieved platelet counts of 50,000 per microliter or more for an average of 13.8 weeks in the splenectomized group and 15.2 weeks in the non-splenectomized group compared with 0.2 and 1.3 weeks for subjects in the respective placebo groups. Significantly more subjects in the placebo group received rescue treatment to increase platelet counts to prevent or treat bleeding compared to the Nplate-treated subjects (57% placebo versus 26% Nplate-treated splenectomized group; 62% placebo versus 17% Nplate-treated non-splenectomized group) (p less than 0.0001). Adverse event rates were similar between the Nplate and placebo groups. A BLA is currently under review by the FDA.
December 3, 2007
GlaxoSmithKline reported positive results from two phase II trials of Promacta for the treatment of chronic hepatitis C-associated thrombocytopenia and chronic Idiopathic thrombocytopenic purpura (ITP). The first study was an international, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. A total of seventy-four HCV-infected subjects with platelet counts between 20,000 and 70,000/mL were enrolled. The subjects received Promacta (30mg, 50mg, or 75mg daily) or placebo for four weeks (pre-antiviral phase). The primary endpoint was platelet count increase to greater than or equal to 100,000/mL at week four. The subjects could then initiate antiviral therapy and continue Promacta or placebo for 12 additional weeks (antiviral phase). The primary endpoint was reached by 75%, 79% and 95% of subjects in the Promacta 30mg, 50mg and 75 mg groups respectively, compared to no platelet elevations in the placebo group (p<0.001). Treatment was generally well tolerated, with all adverse events mild to moderate in nature. The second trial was a multicenter, randomized, double-blind, placebo-controlled study. A total of 118 subjects with chronic ITP and platelet counts <30,000/mL and who had relapsed or were refractory to at least one ITP treatment were enrolled. The subjects received once-daily oral Promacta (30mg, 50mg, or 75 mg) or placebo. The primary endpoint was the proportion of subjects with a platelet count greater than or equal to 50,000 per cubic millimeter after up to six weeks of therapy. The primary endpoint was achieved in 28%, 70% and 81% of subjects who received Promacta (30mg, 50mg and 75mg, respectively) compared to 11% of the placebo group <0.001). Platelet counts rose to greater than 200,000/L in 4% of the placebo-treated subjects and in 14%, 37% and 50% of the Promacta 30mg, 50mg and 75mg-treated subjects, respectively. Treatment was generally well tolerated. Phase III trials of Promacta are currently underway.
June 18, 2007
GlaxoSmithKline reported positive results from a phase III trial of Promacta for the treatment of chronic idiopathic thrombocytopenic purpura (ITP). This international, randomized, double-blind, placebo-controlled trial enrolled 114 subjects with chronic ITP and baseline platelet counts of <30,000/microliter who had failed previous therapy. Subjects received Promacta (50 mg) or placebo once daily for six weeks. The Promacta dose could be increased to 75 mg in subjects not responding after an initial three weeks of treatment. Platelet counts were assessed weekly and up to six weeks following treatment. A platelet count of more than 50,000/microliter was achieved by 59% of the subjects receiving Promacta versus 16% of those on placebo. In addition, a significantly lower incidence of bleeding events during treatment was observed in the Promacta arm compared to placebo (p=0.029) with clinically significant bleeding (WHO Grades 2-4) observed in fewer Promacta subjects (16%) than placebo subjects (36%). GlaxoSmithKline is currently conducting several other phase III trials with Promacta.