Receptos, Inc. announced that the Phase 2 portion of the RADIANCE trial of its selective S1P1 receptor modulator, RPC1063, in relapsing multiple sclerosis (RMS) met the primary endpoint, reduction in MRI brain lesion activity. The overall safety profile of RPC1063 was consistent with the results of prior trials, and continues to support the differentiation of the drug candidate against other oral agents for treatment of RMS on the market or in clinical development.
The randomized, double-blind study assessed the efficacy, safety and tolerability of two orally administered doses (0.5 mg and 1.0 mg) of RPC1063 against placebo in 258 patients with RMS across 77 sites in 13 countries. The primary endpoint of the trial was the reduction in the cumulative number of total gadolinium-enhancing (GdE) lesions determined by MRI from week 12 to week 24 of study treatment, a standard endpoint for Phase 2 trials in this indication. Patients on RPC1063 experienced a statistically significant reduction in GdE lesions of 86% at both 0.5 mg and 1.0 mg compared to patients on placebo (p-values <0.0001 for each dose group compared to placebo). Secondary endpoints measuring effects on other MRI parameters were also positive and statistically significant (p<0.0001 for each dose group compared to placebo). Although this Phase 2 portion of the trial was not powered to detect a statistically significant difference between RPC1063 treatment arms and placebo on annualized relapse rate (ARR), there was a favourable trend for both RPC1063 dose groups. The detailed results of the Phase 2 portion of the RADIANCE trial are expected to be presented at a major scientific meeting in coming months.
Safety and tolerability data from the trial provide support for a differentiated, potential best-in-class profile. The overall adverse event profile appeared relatively similar between the RPC1063 dose groups and placebo with no concerning safety signals for patients receiving RPC1063. First dose changes in heart rate in patients receiving RPC1063 were generally modest (maximum mean reduction).
"The results of this trial demonstrated a significant treatment effect of RPC1063 at both doses, consistent with other molecules in the class," said Jeffrey Cohen, M.D., Principal Investigator of the RADIANCE trial and director of the Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research. "The results also showed a favourable overall safety profile, particularly in the critical areas of cardiovascular and hepatic side effects. The ongoing Phase 3 trial has been designed to confirm and extend these results."
Receptos initiated the Phase 3 portion of the RADIANCE trial under a Special Protocol Assessment (SPA) with the FDA in December 2013. The Phase 3 portion of the trial, which is currently enrolling patients, is a randomized, double-blind study designed to compare 0.5 mg and 1.0 mg of RPC1063 against interferon beta-1a (Avonex®) in 1,200 patients with RMS.
"The positive results of the Phase 2 portion of RADIANCE exceeded our expectations with respect to the differentiation thesis for RPC1063," said Faheem Hasnain, President and Chief Executive Officer of Receptos. "Based on our analysis of the Phase 2 dataset, we believe that RPC1063 has the opportunity to be the best-in-class S1P receptor modulator. Our Phase 3 program is now well underway, positioning the program as the most advanced S1P receptor modulator in development for relapsing multiple sclerosis. In addition, we believe that RPC1063 may have promise in other therapeutic areas, and we continue to look forward to the results of TOUCHSTONE, our Phase 2 trial of RPC1063 in ulcerative colitis, in the fourth quarter of 2014."
Source: MarketWatch Copyright © 2014 MarketWatch, Inc (10/06/14)
Receptos, Inc. announced today that the Company has enrolled the first patients in the Phase 3 portion of RADIANCE, its Phase 2/3 study of RPC1063 in relapsing multiple sclerosis (RMS). The announcement follows the review of interim analysis of the Phase 2 portion of the study which was announced in December 2013.
The RADIANCE Phase 2/3 study was designed to accelerate the RMS clinical development program for RPC1063 by allowing advancement into Phase 3 in a rapid fashion and eliminating the delay that typically exists between the completion of a Phase 2 study and the initiation of a subsequent Phase 3 study. Many of the clinical trial sites involved in the Phase 2 portion of the study are also participating in the Phase 3 portion of the study, allowing for efficient enrollment of Phase 3 patients that are separate from the Phase 2 patient population. In addition, Receptos has obtained Special Protocol Assessment (SPA) agreement from the US Food and Drug Administration on the clinical trial design for both the Phase 3 portion of RADIANCE as well as a second planned RMS Phase 3 study. The second Phase 3 study is planned to begin after announcement of the top-line results of the Phase 2 portion of the RADIANCE study, which is expected to occur in mid-2014.
"Our initiation of Phase 3 positions RPC1063 as the potential next-to-market sphingosine 1-phosphate 1 receptor (S1P1R) modulator for the treatment of relapsing multiple sclerosis," said Faheem Hasnain, President and Chief Executive Officer of Receptos. "Since the founding of Receptos in 2009, we have made rapid progress in the development of RPC1063, which we believe may represent a best-in-class molecule in the S1P1R modulator class. In addition to the top-line results of the Phase 2 portion of RADIANCE, we also look forward in mid-2014 to the top-line results of TOUCHSTONE, our Phase 2 study of RPC1063 in ulcerative colitis, as well as continued progress with our pipeline programs."
RPC1063 is a novel, oral, once daily, selective and potent sphingosine 1-phosphate 1 receptor (S1P1R) modulator in development for autoimmune indications. The Phase 2 portion of the RADIANCE study is a randomized, double-blind study designed to compare 0.5 mg and 1.0 mg of RPC1063 against placebo in patients with RMS. While the Phase 2 study was originally designed to enroll 210 patients, the trial over enrolled a total of 258 patients and completed enrollment on time in October 2013. The Phase 3 portion of the trial is a randomized, double-blind study designed to compare 0.5 mg and 1.0 mg of RPC1063 against interferon beta-1a (Avonex(R)) in 1,200 patients with RMS. Receptos is also enrolling a randomized Phase 2 study, called TOUCHSTONE, examining the efficacy, safety and tolerability of RPC1063 in ulcerative colitis (UC). Top-line results for both studies are expected in mid-2014.
Source: MarketWatch Copyright © 2014 MarketWatch, Inc (07/01/14)