In July, Johnson & Johnson teased data from a head-to-head study showing its multiple sclerosis (MS) candidate ponesimod bested Sanofi’s Aubagio at reducing flare-ups that worsen patients' symptoms. Now, the company is unveiling those data, which will support regulatory filings for the drug in the U.S. and Europe.
Ponesimod, an S1P1 immunomodulator, hit the primary endpoint of lowering patients' annualized relapse rate, or the average number of relapses a person faces a year. The rate for ponesimod patients was 0.202 relapses per year versus 0.290 for the Aubagio group, an improvement of 31%.
The study, presented at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), tested a 20 mg dose of ponesimod against the labeled 14 mg dose of Aubagio (teriflunomide) in adults with the relapsing form of MS over two years. These patients suffer unpredictable relapses of their disease, Luc Truyen, global head of development and external affairs for neuroscience at Johnson & Johnson’s Janssen unit, told FierceBiotech.
“These acute bouts of neurological dysfunction are caused by inflammatory lesions in the brain and spinal cord emerging,” Truyen said. Though the effects of a relapse differ from patient to patient, Truyen said they could include loss of sight, loss of feeling in the leg or difficulty walking.
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“Before the advent of treatments in the early 1990s, the average relapse rate was about 1.5 per year in a typical relapsing-remitting patient. Today, based on the available therapies, this has been reduced to about 0.3 relapses per year, which is already a significant improvement,” Truyen said. “What we’ve done here in this trial is compare teriflunomide—which has a known positive effect on relapse rate—at its labeled dose with ponesimod. The outcome over two years of this study is we reduced the annualized relapse rate by a third, or 30.5%, on top of what teriflunomide has already done.”
The drug also outdid Aubagio at reducing fatigue as measured by The Fatigue Symptoms and Impacts Questionnaire–Relapsing Multiple Sclerosis, a patient-reported questionnaire designed to assess fatigue-related symptoms and how they affect people with MS. The investigators looked at results for a prespecified time point and found that the fatigue of ponesimod patients stabilized, while that of the Aubagio patients worsened over time.
Ponesimod also curbed the number of active lesions by 56% over Aubagio. These lesions can be seen on an MRI and serve as a surrogate endpoint for MS activity; they include new lesions, or new areas of inflammation, as well as lesions that are “lit up” by gadolinium, a contrast agent that doesn’t cross the blood-brain barrier in healthy people.
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“In the context of what is available, I’ll almost quote a statement made in the keynote address (at ECTRIMS): We need to start treatment earlier with more efficacious therapies,” Truyen said. J&J’s advisers think that, on the strength of its data, ponesimod should be considered as an option for newly diagnosed patients, he said.
Ponesimod was one of two late-stage programs J&J picked up in its $30 billion buyout of Actelion in 2017. Last year, the company pulled the plug on a phase 3 trial of the other asset, a treatment for Clostridium difficile-associated diarrhea, leaving ponesimod as its last chance to turn a profit on pipeline products from that deal.
Ponesimod isn’t Aubagio’s only challenger. Just last month, Novartis announced that Arzerra, an injectable cancer drug it picked up in its 2015 asset swap with GlaxoSmithKline, outshone Aubagio in phase 3. The study included more than 1,800 patients and found that Arzerra reduced the rate of relapses.
Novartis aims to file Arzerra for approval in MS by the end of this year. If it gets across the finish line, it would be a turnaround for the cancer med that stumbled in chronic lymphoblastic leukemia. Facing competition from J&J and AbbVie’s Imbruvica, Novartis and partner Genmab stopped marketing it outside the U.S. in 2018. The Big Pharma will present full data for Arzerra at ECTRIMS on Friday.