On 28 October at the 7th Joint ECTRIMS-ACTRIMS conference held in Paris, Celgene presented detailed results from two Phase III trials, SUNBEAM and RADIANCE Part B, for its pipeline blockbuster candidate, ozanimod. In both trials, ozanimod confirmed its efficacy at reducing relapses and disease progression in comparison with Biogen’s Avonex (interferon beta-1a, or IFN) in patients with relapsing-remitting multiple sclerosis (RRMS).
Ozanimod is a second-generation S1P receptor inhibitor that specifically targets the S1P-1 and 5 subtypes. Inhibition of the S1P-1 receptors prevents immune cells from migrating to the brain and, in turn, reduces their attacks on neurons in the brain. Ozanimod is thought to have a better safety profile than the popular oral agent Gilenya from Novartis, which is an unspecific S1P receptor inhibitor that exhibits cardiovascular side effects.
The SUNBEAM study evaluated two doses (1mg and 0.5mg) of ozanimod in 1,346 patients with RRMS for at least one year. A significant reduction in annualized relapse rate (ARR) was demonstrated for both the 1mg dose (ARR = 0.18, p < 0.0001) and for the 0.5mg dose (ARR = 0.24, p = 0.0013) compared with IFN (ARR = 0.35) over an average of 13.6 months of treatment. Additionally, safety and tolerability is comparable to Avonex, and no second degree or higher atrioventricular blocks were reported, which was a key issue with Gilenya.
In the RADIANCE Part B Phase III trial, which had a longer duration, a total of 1,320 patients were randomized and treated with 1mg or 0.5mg ozanimod for two years. Both doses reduced ARR (ARR = 0.172 and ARR = 0.218 for 1mg and 0.5mg, respectively) compared with Avonex (ARR = 0.276) (p < 0.0001, p = 0.0168, respectively) over two years of treatment. Similarly, the incidence of adverse events (AEs), serious AEs, and AEs leading to discontinuation was comparable across treatment groups.
Celgene purchased Receptos in 2015 for $7.2bn to add ozanimod to its pipeline. The latest data from the two Phase III trials, although largely expected, confirmed its superior efficacy and comparable safety profile vs. Avonex. Celgene is on track to begin the global registration process by the end of 2017 in the US and by the first half of 2018 in the EU. According to GlobalData, ozanimod is likely to be a major product for the treatment of RRMS and is expected to reach blockbuster status. This is good news for Celgene, as the company’s stock price took a tumble recently when its promising pipeline asset for the treatment of Crohn’s disease, mongersen, failed in Phase III.
GlobalData (2017). PharmaPoint: Multiple Sclerosis – Global Drug Forecast and Market Analysis to 2026, to be published