Janssen Submits NDA for New Multiple Sclerosis Drug
MARCH 20, 2020
Husseini Manji, MD
Janssen Pharmaceutical Companies of Johnson & Johnson has submitted its New Drug Application (NDA) to the US Food and Drug Administration (FDA) for ponesimod for the treatment of adults with relapsing multiple sclerosis (MS).
The investigational oral drug is a selective sphingosine-1-phosphate receptor 1 (S1P1) modulator that functionally inhibits S1P activity and reduces circulating lymphocytes. The drug was previously submitted to the European Medicines Agency for approval, as well.
The NDA is based off of data from the phase 3 OPTIMUM study, a head to head trial that examined the safety and efficacy of 20 mg ponesimod against 14 mg teriflunomide (Aubagio) in adults with relapsing MS.
The data, which were presented at the 2019 ECTRIMS annual meeting, showed a 30.5% greater reduction in annualized relapse rate (ARR) with treatment with ponesimod compared with teriflunomide at week 108. ARRs for ponesimod and teriflunomide were 0.202 and 0.290, respectively (P = .003).
The investigational treatment also showed positive impacts on secondary end points, including fatigue-related symptoms as assessed with the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS), an MS-specific, 20-item patient-reported outcome measure. At week 108, scores suggested statistically significant effects on symptoms of fatigue with ponesimod treatment compared with teriflunomide, with a mean difference of –3.57 (P = .0019).
“Fatigue is one of the most common and debilitating symptoms of MS and yet, it's one of the most challenging to manage and treat," said Husseini Manji, MD, FRCPC, Global Therapeutic Area Head for Neuroscience at Janssen Research & Development, LLC, in a statement. "We were thrilled to see improvement in fatigue-related symptoms as part of the Phase 3 OPTIMUM trial as we know the profound impact it may have on a person's daily life. The improvement in fatigue, coupled with reduction in ARR, demonstrate great promise for ponesimod with patients seeking a more targeted treatment option."
In addition, treatment with ponesimod was associated with a 56% reduction in cumulative number of combined unique active lesions (P <.001). The most common adverse events recorded were nasopharyngitis, headache, upper respiratory tract infections, and an increase in alanine aminotransferase.
It is an especially stressful time for MS patients as immunocompromised patients are particularly vulnerable to the coronavirus (COVID-19).
Robert Fox, MD, neurologist at the Mellen Center for MS and vice chair for research at the Neurological Institute at Cleveland Clinic, explained in an interview with NeurologyLive what hospitals are doing to counsel patients through the pandemic, while providing guidance to staff to help prevent the spread of the virus.
“At this point, the Mellen Center at the Cleveland Clinic is recommending that patients not cancel, interrupt, or delay scheduled doses of their MS medication. We believe that the way the medications work, the duration of action of these medications, and the risks of MS disease activity coming back are all reasons to continue MS therapies without interruption,” Fox said. “Given what we know about the current risks of COVID-19, MS therapy interruptions appear more likely to be harmful than helpful.”
This sentiment is echoed by several other MS centers including Stanford’s Multiple Sclerosis and Neuroimmunology Program, which has advised patients that “there is no reason to change or avoid medications pertaining to the treatment of multiple sclerosis. The CDC standard recommendations for minimizing exposure risk remain in effect.”
The National Multiple Sclerosis Society has also provided guidance for patients, advising that if they are currently taking a DMT and are concerned about COVID-19, “do not stop your DMT without first speaking with your MS provider.”