Janssen Seeks FDA Approval for Oral Ponesimod for Treating Relapsing MS

Marisa Wexler MS avatar

by Marisa Wexler MS |

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ponesimod, NDA submission

Janssen has submitted an application to the U.S. Food and Drug Administration (FDA) asking for ponesimod to be approved as an oral treatment for adults with relapsing multiple sclerosis (MS).

Ponesimod, formerly ACT-128800, is an experimental treatment that targets the protein sphingosine-1-phosphate receptor 1 (S1P1) with reportedly high selectivity. By doing so, it “traps” immune cells in lymph nodes (immune-related structures), which prevents them from doing damage to the nervous system.

The New Drug Application submitted to the FDA is based on data from the pivotal Phase 3 OPTIMUM clinical trial (NCT02425644). This trial compared the efficacy and safety of ponesimod to those of Aubagio (teriflunomide), an approved first-line therapy for MS marketed by Sanofi.

Like ponesimod, Aubagio works by reducing the activity of the immune system, albeit through different mechanisms.

OPTIMUM enrolled 1,133 people with relapsing-remitting MS (RRMS) or active secondary progressive MS (SPMS). The participants were randomly assigned to receive either ponesimod at 20 mg or Aubagio at 14 mg, both taken by mouth once a day for 108 weeks (two years).

Topline results from OPTIMUM demonstrated a significant reduction in the average annualized relapse rate (ARR) with ponesimod, as compared with Aubagio — 0.202 relapses per year for ponesimod versus 0.290 for Aubagio. That’s a 30.5% decrease with ponesimod compared with Aubagio.

Ponesimod treatment, as compared with therapy with Aubagio, also significantly reduced (by 56%) the average number of new, active, inflammatory brain lesions visible on magnetic resonance imaging (MRI). There also was a trend toward less disability progression with ponesimod, but this result did not reach statistical significance.

Importantly, ponesimod treatment led to a statistically significant reduction in fatigue relative to Aubagio, as assessed with a new scale — the Fatigue Symptoms and Impacts Questionnaire-Relapsing Multiple Sclerosis, or FSIQ-RMS.

“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,” Husseini Manji, MD, the global therapeutic area head for neuroscience at Janssen Research & Development, part of Johnson & Johnson, said in a press release.

“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,” Manji said.

In OPTIMUM, the safety profile of ponesimod was consistent with that reported in previous trials, and with the known safety profile of other S1P receptor modulators.

“In the coming months, we’ll work closely with the FDA to bring ponesimod one step closer to the MS patient community, and remain encouraged by its superior efficacy profile – specifically in reducing new inflammatory lesions and disability accumulation – in comparison to a leading therapy on the market,” said Mathai Mammen, MD, PhD, the global head of Janssen Research & Development.

Janssen recently submitted a similar application for ponesimod to the European Medicines Agency (EMA), seeking the therapy’s approval in the EU.

Multiple Sclerosis News Today had the opportunity to recently interview Luc Truyen, MD, PhD, global head of development and external affairs for neuroscience at Janssen. Find the interview on this link.

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