The FDA approved oral ponesimod (Ponvory) to treat relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, drugmaker Janssen announced Friday.
Ponesimod is a selective modulator of the sphingosine-1 phosphate receptor, like two other approved MS drugs, fingolimod (Gilenya) and siponimod (Mayzent). Binding of the drug to the receptor lowers the number of circulating lymphocytes by trapping them in the lymph nodes, reducing the number of lymphocytes that could enter the central nervous system and damage myelin.
In contrast to fingolimod’s longer half-life, ponesimod leaves the blood within 1 week if treatment needs to be stopped, with effects on the immune system wearing off in 1 to 2 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,” Janssen (a Johnson & Johnson company) said in a press release. Most patients do not need genetic testing or first-dose monitoring with ponesimod.
The FDA’s approval was based in part on the 2-year, phase III OPTIMUM trial of relapsing MS patients that used an active control. In that study, ponesimod 20 mg reduced annual relapse rate (ARR) by 30.5% over teriflunomide (Aubagio) 14 mg. At 108 weeks, ponesimod 20 mg had an ARR of 0.202, compared with an ARR for teriflunomide of 0.290 (P=0.0003).
Ponesimod also reduced the number of new inflammatory lesions on MRI by 56% compared with teriflunomide (P>0.0001) and showed effects on fatigue based on a patient-reported outcome instrument, the Fatigue Symptoms and Impacts Questionnaire-Relapsing in Multiple Sclerosis. Confirmed disability accumulation was not significantly different between the two groups.
The drug has a proven safety profile and generally has been well-tolerated in clinical studies that total more than 10 years, with overall adverse event rates similar to placebo in phase II and teriflunomide in phase III trials, Janssen said. Most common adverse events in the phase III study were upper respiratory infection, hepatic transaminase elevation, and hypertension.
Ponesimod can increase risk of serious infections, the drug company warned. Breathing problems, liver problems, hypertension, skin cancer, or macular edema may occur. Patients also may experience bradycardia or bradyarrhythmia when they first start taking the drug.