(c) Ophthotech

Ophthotech Announces Results from Pivotal Phase 3 Trials of Fovista ® in Wet AMD

Ophthotech Corporation has announced that the pre-specified primary endpoint of mean change in visual acuity at 12 months was not achieved in its two pivotal Phase 3 clinical trials investigating superiority of Fovista (pegpleranib) anti-PDGF therapy in combination with Lucentis (ranibizumab) anti-VEGF therapy compared to Lucentis monotherapy for the treatment of wet age-related macular degeneration (AMD). The addition of Fovista to a monthly Lucentis regimen did not result in benefit as measured by the mean change in visual acuity at the 12 month time point.

The two clinical trials (OPH1002 and OPH1003) were international, multicenter, randomized, double-masked, controlled Phase 3 studies evaluating the safety and efficacy of 1.5 mg of Fovista administered in combination with Lucentis (Fovista combination therapy) compared to Lucentis monotherapy. In each of these trials, patients were randomized to one of two approximately equal sized treatment groups. The two Phase 3 trials enrolled an aggregate of 1,248 patients with wet AMD. The results from the databases of the two trials were unmasked and analyzed concurrently.

The combined analysis from the two trials (OPH1002 and OPH1003) showed that patients receiving Fovista combination therapy gained a mean of 10.24 letters of vision on the Early Treatment of Diabetic Retinopathy Study (ETDRS) standardized chart at 12 months, compared to a mean gain of 10.01 ETDRS letters for patients receiving Lucentis monotherapy, a difference of 0.23 ETDRS letters. In OPH1002, consisting of 619 treated patients, subjects receiving Fovista combination therapy gained a mean of 10.74 letters of vision on the ETDRS standardized chart at 12 months, compared to a mean gain of 9.82 ETDRS letters in patients receiving Lucentis monotherapy, a resulting difference of 0.92 ETDRS letters (p=0.44). In OPH1003, consisting of 626 treated patients, subjects receiving Fovista combination therapy gained a mean of 9.91 letters of vision on the ETDRS standardized chart at 12 months, compared to a mean gain of 10.36 ETDRS letters in patients receiving Lucentis monotherapy, a resulting difference of -0.44 ETDRS letters (p=0.71). None of these results of the pre-specified primary efficacy analysis were statistically significant.

In the pooled analysis of pre-specified secondary endpoints from both trials, 24.2% of patients receiving Fovista combination therapy gained 20 or more ETDRS letters from baseline at month 12, compared to 22.1% of patients receiving Lucentis monotherapy. In OPH1002, 25.9% of patients receiving Fovista combination therapy gained 20 or more ETDRS letters from baseline at month 12, compared to 20.0% of patients receiving Lucentis monotherapy. In OPH1003, 22.5% of patients receiving Fovista combination therapy gained 20 or more ETDRS letters from baseline at month 12, compared to 24.1% of patients receiving Lucentis monotherapy.

In the pooled analysis, 12.1% of patients receiving Fovista combination therapy lost 5 or more ETDRS letters from baseline at month 12, compared to 11.2% of patients receiving Lucentis monotherapy. In OPH1002, 12.0% of patients receiving Fovista combination therapy lost 5 or more ETDRS letters at month 12, compared to 12.3% of patients receiving Lucentis monotherapy. In OPH1003, 12.2% of patients receiving Fovista combination therapy lost 5 or more ETDRS letters at month 12, compared to 10.2% of patients receiving Lucentis monotherapy.

In addition, in the pooled analysis, 13.5% of patients receiving Fovista combination therapy achieved visual acuity of 20/25 or better at month 12, compared to 13.9% of patients receiving Lucentis monotherapy. In OPH1002, 13.6% of patients receiving Fovista combination therapy achieved visual acuity of 20/25 or better, compared to 13.2% of patients receiving Lucentis monotherapy. In OPH1003, 13.5% of patients receiving Fovista combination therapy achieved visual acuity of 20/25 or better, compared to 14.6% of patients receiving Lucentis monotherapy.

Based on a preliminary analysis of the safety data from these two trials, Fovista combination therapy and Lucentis monotherapy were generally well tolerated after one year of treatment. The ocular adverse events more frequently reported in the Fovista combination therapy group compared to the Lucentis monotherapy group were mainly related to the injection procedure. The incidence of reported serious systemic adverse events was generally similar in both treatment groups as was the incidence of myocardial infarction or cerebrovascular accident.

Note: Fovista is a registered trademark with Ophthotech, while Lucentis is a registered trademark of Genentech.

Posted in Age-related Macular Degeneration, Pharmaceuticals/Drugs and tagged , , , .