The U.S. Food and Drug Administration ( FDA ) has approved Ponvory ( Ponesimod ), a once-daily oral selective sphingosine-1-phosphate receptor 1 ( S1P1 ) modulator, to treat adults with relapsing forms of multiple sclerosis ( MS ), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease.
The FDA approval is based, in part, on a two-year, head-to-head Phase 3 clinical trial in which Ponesimod 20 mg has demonstrated superior efficacy in significantly reducing annual relapses by 30.5% compared to Teriflunomide ( Aubagio ) 14 mg in patients with relapsing multiple sclerosis.
Over the study period, 71% of patients treated with Ponesimod had no confirmed relapses, compared to 61% in the Teriflunomide group.
Ponesimod was also superior to Teriflunomide in reducing the number of new Gadolinium-enhancing ( GdE ) T1 lesions and the number of new or enlarging T2 lesions by 59% and 56%, respectively. GdE T1 lesions and T2 lesions are identified using magnetic resonance imaging (MRI) technology and are recognized as classic measures of multiple sclerosis pathology that can provide insights into disease activity and disease burden, respectively.
The difference in rates of disability progression was not statistically significant between the Ponesimod and Teriflunomide groups.
If treatment needs to be stopped, Ponesimod leaves the blood within one week, with effects on the immune system wearing off in one to two weeks for most patients.
This may offer additional flexibility in treatment management if patients need to receive vaccines, address potential infections, or begin family planning.
Ponesimod has no known food restrictions and requires no genetic testing or first-dose monitoring for most patients.
Ponesimod has a proven safety profile and was generally well-tolerated over multiple clinical studies totaling more than 10 years, with overall adverse event rates similar to placebo in the phase 2 and Teriflunomide in the phase 3 trials.
The most common adverse events observed in the phase 3 trial in Ponesimod-treated patients were upper respiratory infection, hepatic transaminase elevation and hypertension.
The OPTIMUM ( Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis ) trial was a head-to-head, prospective, multicenter, randomized, double-blind phase 3 study comparing efficacy, safety and tolerability of Ponesimod 20 mg versus Teriflunomide 14 mg in adults with relapsing multiple sclerosis.
The primary endpoint of the study, which included 1,133 participants, was the annualized relapse rate ( ARR ) from baseline through the study period.
The study included several other important efficacy endpoints, including the number of new Gd-enhancing T1 lesions from baseline to week 108, the number of new or enlarging T2 lesions from baseline to week 108, and the time to 3-month and 6-month confirmed disability progression. ( Xagena )
Source: Janssen Pharmaceutical, 2021