Janssen, a subsidiary of Johnson & Johnson, presented positive top-line results from the Phase III OPTIMUM study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Stockholm.
The study evaluated the efficacy and safety of ponesimod compared to Aubagio (teriflunomide) in adults with relapsing multiple sclerosis (RMS). Ponesimod is also under development for the treatment of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS), and in this study met its primary and most secondary endpoints.
OPTIMUM was a head-to-head, prospective, multicenter, randomised, double-blind, active-controlled, parallel-group, Phase III study to compare the efficacy, safety and tolerability of ponesimod 20mg versus teriflunomide 14mg in adults with RMS. The study included 1,133 participants with a treatment duration of 108 weeks. The primary endpoints of OPTIMUM were annualised relapse rate (ARR) up to the end of the study and the change from baseline to Week 108 in fatigue-related symptoms. Moreover, the study evaluated other secondary endpoints: cumulative number of combined unique active lesions (CUALs) using magnetic resonance imaging (MRI), time to first 12-week confirmed disability accumulation (CDA), and time to first 24-week CDA from baseline to end of the study. Sphingosine 1-phosphate (S1P) receptor modulators are well known to be safe and ponesimod confirmed its safety profile during the OPTIMUM study.
Ponesimod is a sphingosine 1-phosphate type 1 (S1P-1) receptor agonist and blocks the leaving of lymphocytes from lymph nodes. In this way, it reduces the availability of circulating effector T cells that can invade target organs, and activation of S1P1Rs also prevents demyelination by reduction of chemotactic chemokine release.
Ponesimod is an iminothiazolidinone derivative that demonstrated a 10-fold greater potency at the S1P1 receptor, in vitro, than any other S1P receptor subtype. This differentiates ponesimod from Novartis’ first-in-class S1P modulator, Gilenya, which non-specifically modulates S1P1, S1P3, S1P4, and S1P5 receptors.
Ponesimod, which targets an S1P1 receptor, works in a similar way to Celgene’s ozanimod, another pipeline product that is in pre-registration in the US for RMS and EU for RRMS, and could be another option in MS on top of several other older drugs already approved, according to these new data published.
According to GlobalData, ponesimod is expected to be launched in the US in 2020 and it will become the third-in-class S1P receptor modulator behind Gilenya (fingolimod) and ozanimod, as the currently available clinical trial data do not suggest that this drug holds a significant advantage over these two agents.
Furthermore, key opinion leaders (KOLs) interviewed by GlobalData think ponesimod will be another in-class drug and the data published are pretty much the same as the data published for Gilenya and Mayzent. So they do not see anything in there that distinguishes it, or is likely to distinguish it, from an efficacy standpoint nor a probability standpoint. As there will not be any difference in efficacy and tolerability, the competition for these drugs will be mostly on the commercial side, and who works best with the third-party payers in terms of getting their drug on the formularies. Also, at the moment in terms of safety monitoring, physicians have to monitor their patients, but with ozanimod, physicians only do safety monitoring once every six months, and this can be another competitive advantage in favour of ozanimod added to the earlier launch compared to ponesimod.
The MS therapeutics market has entered an exciting phase, with an upsurge of available treatment options and several promising late-stage pipeline products offering diverse mechanisms of action (MOAs). The launch of new therapies will drive growth in the MS space, provide more options for patients, and stimulate further competition.
GlobalData (2019) PharmaPoint: Multiple Sclerosis – Global Drug Forecast and Market Analysis to 2028, to be published.
GlobalData (2018) Multiple Sclerosis Competitive Landscape to 2026, July 2018, GDHC023CL
GlobalData (2018). Multiple Sclerosis: Dynamic Market Forecast to 2026, November 2018, GDHC008FS