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ViroPharma issued results from a phase IV trial of Cinryze for the treatment of hereditary angioedema (HAE). This open-label, multicenter extension study enrolled 146 patients who were treated with Cinryze for up to 2.6 years. Subjects received 1000 units of Cinryze every three to seven days based on the decision of the investigator. Subjects experienced a 93.7% reduction in attacks while taking prophylactic Cinryze (median of 0.19 attacks per month) compared with the median historical rate at baseline (3.0 attacks per month). Some 87.7% reported an attack frequency of one or less attack per month during prophylactic Cinryze and 34.9% had no attacks during the study. Only 7.5% of subjects experienced relatively frequent attacks despite twice-weekly Cinryze. The drug was well tolerated. ViroPharma will publish the results in the September print issue of The American Journal of Medicine.
Shire reported positive results from a phase III trial of icatibant for treatment of acute attacks of hereditary angioedema (HAE). This global, randomized, double-blind, placebo controlled trial, FAST-3, enrolled 88 subjects with moderate to very severe cutaneous and/or abdominal symptoms of HAE. The subjects received a single subcutaneous injection of icatibant 30 mg or placebo following their first attack after enrollment. The primary endpoint, time to onset of symptom relief for the first attack as measured by a composite symptom score assessed by the patient, was reached with statistically significant benefit compared to placebo. The median time to onset of symptom relief for was 2.0 hours for the icatibant arm, compared with 19.8 hours for placebo (p<0.001). Icatibant also provided a significantly shorter time to onset of symptom relief of the primary symptom. This secondary efficacy endpoint was measured by a 30% reduction in symptom score. The median time to onset of relief for icatibant by this measure was 1.5 hours, compared with 18.5 hours for placebo (p<0.001). Icatibant was generally well tolerated.
Dyax issued positive results from a phase III trial of DX-88 for the treatment of hereditary angioedema. This double-blind, placebo-controlled, multi-center study, dubbed EDEMA4, enrolled 96 subjects in the United States and Canada. The subjects received a fixed 30 mg subcutaneous dose of DX-88 or placebo. The primary endpoint was patient reported assessment of individual symptom burden at four hours, measured using the Mean Symptom Complex Severity (MSCS) score. This endpoint showed improvement over placebo (p= 0.010). The secondary endpoint, symptom improvement at four hours measured by a Treatment Outcome Score (TOS), also showed improvement over placebo (p= 0.003). In addition, the proportion of subjects with successful response at four hours was 93.8% for the DX-88-treated group versus 58.3% for the placebo group (p=0.001). The proportion of subjects maintaining significant improvement in overall response was 43.8% for the DX-88-treated group versus 20.8% for the placebo group (p= 0.022). DX-88 was well tolerated with no drug-related serious adverse events reported. Based on positive phase III results, Dyax plans to complete a BLA filing with the FDA early in the fourth quarter of 2008.
Idenix released positive results from a phase I/II trial of IDX899 for the treatment of HIV-1. This study enrolled 30 treatment nave subjects who were randomized in three cohorts 8:2 to receive 800 mg/day, 400 mg/day and 200 mg/day of IDX899 orally once-daily or placebo, for seven days. The subjects receiving daily oral administration of 800 mg, 400 mg and 200 mg IDX899 achieved mean viral load reductions of 1.78, 1.78, and 1.83 log(10), respectively, compared to a mean plasma viral load increase of 0.05 log(10) for placebo. The mean CD4+ count change from baseline increased by at least 60 cells/mm3 for each of the 800 mg, 400 mg and 200 mg dosing cohorts and decreased by about 80 cells/mm3 for patients receiving placebo. Treatment was well tolerated. Based on the antiviral activity of IDX899 seen to date, the study was amended to also evaluate a lower dose of 100 mg/day. Treatment at this dose is currently under evaluation.
Pharming Group issued positive results from a phase III trial of Rhucin for the treatment of Hereditary Angioedema (HAE). This randomized double-blind placebo-controlled study enrolled 39 subjects in North America. On having an acute HAE attack the subjects received one of two doses of Rhucin (100 U/kg, 50 U/kg) or placebo. The primary endpoint was time to beginning of symptom relief. In the subjects who received the 100 U/kg dose of Rhucin, the median first symptom relief was approximately 68 minutes, those that received the 50 U/kg dose reported relief at approximately 100 minutes, and those that received placebo reported symptom relief at approximately 258 minutes. The time to minimal clinical symptoms, the secondary endpoint, was reported by subjects in the 100 U/kg, 50 U/kg, placebo groups at approximately 245, 247, and 1098 minutes, respectively. The primary and secondary endpoint results with both doses of Rhucin were statistically significant relative to placebo (p-values < 0.01). Based on the results Pharming Group plans to meet with EMEA and FDA to accelerate regulatory filings in Europe and the USA.
CSL Behring issued positive results from a phase III trial of C1-INH for the treatment of Hereditary Angioedema (HAE). This randomized, double-blind, placebo controlled trial, dubbed I.M.P.A.C.T. (International Multi-centre Prospective Angioedema C1-inhibitor Trial), enrolled one hundred and twenty five subjects. The subjects received C1-INH at 20 units/kilogram of body weight (U/ kg b.w.), 10 U/ kg b.w or placebo. The primary endpoint was time between start of C1-INH administration and onset of relief of symptoms from abdominal or facial attacks as determined by the subject's assessment. The median time to onset of relief of symptoms in the 20 U/kg b.w. C1-INH treatment group was thirty minutes, compared to 1.5 hours for those who received placebo. The C1-INH 20 U/kg b.w. arm also reached significance in secondary endpoints over placebo. These endpoints included the proportion of subjects with increased intensity of clinical HAE symptoms between two and four hours after start of study drug administration compared to baseline (p= 0.001, one sided), and time to the complete resolution of HAE symptoms (p= 0.024, one sided). The C1-INH 10 U/kg b.w. arm showed improvement over placebo but did not reach significance. Based on the results, CSL Behring plans to file for approval in the US, Canada and Europe.
InterMune released positive results from a phase Ia trial of ITMN-191 for the treatment of hepatitis C. This double-blind, placebo-controlled single ascending dose study enrolled healthy subjects who received single doses of ITMN-191 administered as monotherapy, with and without food. A significantly higher than anticipated plasma level of ITMN-191 was experienced by subjects in dose cohorts of ITMN-191 administered with food. Plasma levels of ITMN-191 were observed in all dose groups and pharmacokinetic modeling suggested a range of potentially efficacious doses for future multi-dose trials. All doses tested were well tolerated with adverse events mild to moderate in nature. Based on positive phase Ia results, InterMune plans to commence phase Ib multi-dose trials.
Lev Pharmaceuticals issued positive results from a phase III trial of Cinryze for the treatment of hereditary angioedema. This 24 week, double-blind, placebo controlled study enrolled 24 subjects who were randomized to receive 12 weeks of Cinryze followed by 12 weeks of placebo or 12 weeks of placebo followed by 12 weeks of Cinryze. All subjects were dosed twice weekly. The primary endpoint was met, with a 53% reduction in the number of attacks for the Cinryze group compared to placebo (p less than0.0001). In addition, Cinryze led to a 66% reduction in days of swelling (p less than0.0001) and decreases in the average severity of attacks (p=0.0008) and average duration of attacks (p=0.0004). Based on these results, Lev intends to file an amendment to a BLA currently under review by the FDA to include Cinryze for the prevention of HAE attacks.
Pharmasset and Roche reported positive results from a phase I trial of R7128 for the treatment of hepatitis C. This trial enrolled 40 subjects with chronically infected hepatitis C who had failed prior interferon therapy. Subjects received placebo or R7182 (750 mg or 1500 mg) administered either once-daily or twice-daily for 14 days as monotherapy. Subjects in the highest dose cohort (1500 mg twice daily) showed the greatest mean decrease in HCV RNA from baseline, with a mean 2.7 log10 IU/mL (>99%) decrease. There was no evidence of viral rebound in any dose cohort throughout the 14 days treatment period. Treatment was generally safe and well tolerated, with no serious adverse events reported. Based on the results Pharmasset and Roche plan to initiate a phase I/II trial of R7128 in September of 2007.
Pharming announced positive results from a phase III trial of Rhucin for the treatment of Hereditary Angioedema (HAE). This double-blind placebo-controlled study was conducted across several sites in Europe. Data is from the first 28 treated subjects who were randomized to either Rhucin or placebo. The primary endpoint, time to beginning of symptom relief, reached statistical significance. The subjects in the Rhucin arm reported first relief at a median time of 60 minutes compared to 8.5 hours for the placebo arm (p=0.0009). The secondary endpoint, time to minimal symptoms, also reached statistical significance,. The Rhucin arm reported minimal symptoms at a median time of 6.1 hours compared with 20.2 hours for the placebo arm (p=0.0038). Treatment was well tolerated, with no reported adverse events. Pharming recently submitted a MAA in Europe and phase III trials are ongoing in the US.
Dyax released positive top-line results from a phase III trial, dubbed EDEMA3, of DX-88 for the treatment of hereditary angioedema (HAE). This 72 subjects internationally and was conducted in two phases: a double-blind, placebo-controlled phase and a repeat dosing phase. In the first phase subjects received either a single 30 mg subcutaneous dose of DX-88 or placebo. After subjects received one treatment in the placebo controlled phase they were eligible for the repeat dosing phase. The primary endpoint, symptom improvement at four hours as measured by the Treatment Outcome Score (TOS), reached statistical significance with a p-value of 0.021. The two secondary endpoints also reached statistical significance. The assessment of individual symptom burden at four hours, as measured using the Mean Symptom Complex Severity score (MSCS) had a p-value of 0.024. Time to significant improvement in overall response, defined as patient reported symptoms as "a lot better" or "resolved" within the first 4 hours, had a median time of 149 minutes for the DX-88 group versus greater than four hours for the placebo group (p=0.044). Treatment was well tolerated, with no drug related serious adverse events. Dyax anticipates FDA approval of DX-88 in the second half of 2008.
Lev issued positive interim results from a phase III trial of C1-INH for thetreatment of hereditary angioedema (HAE). This multi-center, placebo-controlled,double-blind study, dubbed CHANGE (C1-inhibitor in Hereditary AngioedemaNanofiltration Generation evaluating Efficacy), was conducted in two phases. Inthe acute phase, 71 subjects with moderate to severe acute HAE attacks in theface, abdomen or genitals were enrolled. Efficacy and safety parameters wereobserved. In the ongoing prophylactic phase subjects with more severe HAE wereenrolled. Again, safety and efficacy parameters were observed. Treatment waswell tolerated with no drug-related serious adverse events, no immunogenicityand no reported injection site reactions. Results revealed that the primaryendpoint in the acute phase was reached. The median time to sustained symptomrelief of 2.0 hours for subjects receiving C1-INH compared to greater than fourhours for those receiving placebo (p=0.026). Based on the results, Lev plans tofile a BLA with the FDA in Q2 of 2007 for the acute treatment of HAE.
Pfizer reported positive interim data from two phase III trials of maraviroc for the treatment of HIV. Both trials enrolled subjects with CCR5-tropic HIV-1 infection across several international sites. Subjects were randomized to receive maraviroc (once a day or twice a day) along with a background regimen of current HIV therapy or background therapy alone. Of the 601 subjects enrolled in the first study, 60.4% of those who took the twice daily combination treatment achieved a level of less than 400 HIV copies per milliliter of blood, compared to 54.7% on a once-daily dose and 31.4% on just background therapy. The second study enrolled 475 subjects. Results revealed that 61.3% of twice-daily maraviroc subjects achieved target HIV levels, compared with 55.5% on once-daily therapy and 23.1% treated only with background therapy. Full results from both of the trials are expected by the end of 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.
Kos and Jerini reported positive overall preliminary results from two phase III trials, FAST-1 and FAST-2, of Icatibant for the treatment of hereditary angioedema (HAE). The FAST-1 trial was a double-blind, placebo-controlled study that enrolled 56 subjects in the US, Canada, Australia and Argentina. The primary endpoint in this trial, median time to onset of symptom relief, did not reach statistical significance. The subjects receiving Icatibant attained symptom relief in 2.5 hours versus 4.6 hours for placebo (p=0.131). Time to onset of relief of key symptoms showed a statistically significant reduction for skin swelling (p=0.032), skin pain (p=0.007), and abdominal pain (p=0.056). Median time to first improvement of symptoms was 0.8 hours for Icatibant versus 16.9 hours for placebo (p less than 0.001). The FAST-2 trial enrolled 74 subjects in 10 European countries and in Israel. It was designed as a double-blind comparator study with tranexamic acid. This trial reached statistical significance in the primary endpoint of median time to onset of symptom relief. The subjects receiving Icatibant attained symptom relief in 2 hours versus 12 hours for tranexamic acid (p less than 0.001). Time to onset of relief of key symptoms was significant for skin swelling (p less than 0.001), skin pain (p=0.002) and abdominal pain (p=0.028). Median time to first improvement of symptoms was 0.8 hours for Icatibant versus 7.9 hours for tranexamic acid (p less than 0.001). Based on the overall positive results, the companies plan to submit a NDA in December of 2006.
Dyax has issued interim results of a phase II trial of DX-88, for the treatment of hereditary angioedema (HAE). Preliminary data indicate that the drug appears safe and well tolerated, with no drug related serious adverse events reported (in keeping with safety data from other trials of the drug). Furthermore, preliminary evidence of efficacy was also observed: of the 61 HAE attacks observed among the first 34 enrolled subjects, median response time was 35 minutes. No substantial difference was noted between doses with respect to initial response rates (5 mg=92%, n=24; 10 mg=91%, n=22; 20 mg=100%, n=15), but a difference was noted in the durability of response, with just 3% of subjects experiencing “rebound” attacks (attack needing a second dose within 24 hours) at the 10 mg or 20 mg doses, vs. 25% at 5 mg. This ongoing, open-label, dose ranging, repeat dosing trial has to date enrolled 36 subjects across 19 US sites; these patients accou8nted for 85 HAE attacks, 61 of which were included in this interim analysis. Based on these data, and results obtained from two other phase II studies of the drug, Dyax announced plans to initiate a controlled, multicenter, multinational, 48-patient phase III trial of the drug before the end of Q2, 2005.
Dyax and Genzyme have issued positive final results of a phase II trial of DX-88, their investigational treatment for hereditary angioedema (HAE). These results were presented at the Annual Meeting of the American College of Allergy, Asthma and Immunology. Trial results indicate that the drug met its primary efficacy endpoint, with 72% of patients treated with DX-88 (n=40) reporting significant improvements in HAE symptoms within four hours of administration, as opposed to a 25% of patients receiving placebo (n=8), a statistically significant difference for all dose groups (p=0.0169). Secondary immunological endpoints were also met, with multiple administrations of DX-88 producing no detectable antibody response to the drug. Median time to onset of relief across all types of HAE attacks was 70 minutes for the DX-88 group, vs. 246 minutes for placebo. The double-blind, placebo-controlled, dose-escalating trial evaluated the safety and efficacy of four dose regimens of DX-88 (5, 10, 20 and 40 mg/m2) or placebo via 10-minute intravenous infusion in 48 patients with a confirmed history of HAE. The companies announced that the results from this trial would be used to support an ongoing, expanded phase II follow-up trial.
Jerini has issued the results from a phase II study of icatibant, for the treatment of hereditary angioedema (HAE). Results demonstrated that icatibant was efficacious in rapidly relieving acute HAE attacks when administered either intravenously or subcutaneously. The study treated a total of 20 HAE attacks, 12 via intravenous administration and 8 via subcutaneous injection; no difference in efficacy was observed between the groups, and the drug was safe and well tolerated. Jerini announced that they planned to pursue phase III development in the near future with the subcutaneous formulation, which would ultimately allow HAE sufferers to treat attacks at home, without the need to see a doctor.
Dyax and Genzyme announced preliminary results of their phase II trial of DX-88, their kallikrein inhibitor for the treatment of hereditary angioedema. Results from the first subject cohort have met the primary endpoint, significant improvement over placebo in symptoms of acute attacks within four hours. The double-blind, placebo controlled study had to date enrolled 105 subjects and delivered over 140 doses, among whom the drug was found to be safe and well tolerated, with an adverse event profile similar to placebo. There is currently no FDA-approved treatment for hereditary angioedema, and DX-88 has been granted Orphan Drug status for this indication.