J&J nabs FDA nod for Ponvory, joining Novartis, Bristol Myers in crowded MS market

Another oral multiple sclerosis drug is here, challenging a slate of existing players that includes heavyweights Novartis, Bristol Myers Squibb, Sanofi and Biogen.

Johnson & Johnson’s newly FDA-approved Ponvory, also known as ponesimod, is yet another S1P modulator to enter the U.S., joining Novartis’ aging blockbuster Gilenya and its follow-on Mayzent, as well as Bristol Myers’ newly approved Zeposia.

And it’s “similar in price point to other treatments,” a company media aide said after the approval announcement. But the J&J drug has a set of phase 3 data those competitors don’t have—a head-to-head win against Sanofi’s blockbuster pill Aubagio.

In a phase 3 study, a daily dose of Ponvory cut annual relapses by 30.5% over Aubagio, a widely used but older medicine. After two years, 71% of patients who got Ponvory had no confirmed relapses, compared with 61% for the Aubagio group. Plus, Ponvory showed it was better in terms of visible disease activity as shown on MRI. And Ponvory sported a numerical benefit in preventing disability from worsening.

But without other head-to-head studies, it’ll be difficult to compare Ponvory’s efficacy with its direct rivals in the S1P class. Zeposia, for example, got its FDA go-ahead in relapsing MS based on clinical data comparing it with Biogen’s Avonex. But Ponvory does boast one advantage.

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Patients who received Ponvory can have their lymphocyte counts start to return to normal in one week after stopping treatment, which is shorter than its other in-class rivals, Allitia DiBernardo, M.D., global head of medical affairs of neurology at J&J’s Janssen pharma unit, said in an interview. S1P modulators work by blocking the excretion of lymphoid immune cells from entering the central nervous system to cause an inflammatory response.

The fast reversibility is relevant in many situations, including vaccinations and family planning, because it can quickly give a patient a fully reconstituted, circulating immune population, DiBernardo explained.

But then again, Ponvory’s rival list extends beyond the oral S1P class. Roche’s CD20-targeted injectable Ocrevus is quickly establishing itself as the new MS leader with 2020 sales of CHF 4.33 billion ($4.66 billion), thanks to a 24% year-over-year growth. And Novartis just launched its rival CD20 therapy Kesimpta.

RELATED: Bristol Myers Squibb's Zeposia launches into crowded MS market

The CD20 class is believed to be more potent than existing S1Ps at controlling MS. To make life difficult for Ponvory, Kesimpta has its own Aubagio head-to-head data—and it looks better than Ponvory’s.

In its own studies, once-monthly, self-administered Kesimpta cut annual relapse rates by 50.5% in one phase 3 and 58.5% in another when compared with Aubagio.

DiBernardo stressed that there’s still room for new entrants such as Ponvory despite the multiple options already on the market. “One in four MS patients discontinue their disease-modifying treatment before even completing one year, and to me that speaks to the unmet need for better agents,” she said.

In an ongoing extension of its phase 2 trial, more than 50% of patients who elected to remain in this study were still on the approved 20-mg dose after more than eight years, according to the most recent analysis, she pointed out.

That fast immune cell recovery also holds relevance in Ponvory’s comparison with the CD20 drug class, DiBernardo said. While the new J&J drug only tucks lymphocytes away by blocking their trafficking, CD20 drugs work by depleting B cells, which means it takes even longer for immune cells to return to normal level.

In the end, different patients may choose the best drug that suits them. And many drugs are vying for share beyond the S1P and CD20 drugs including Merck KGaA’s Mavenclad, and Biogen’s Tecfidera and follow-on Vumerity.

Editor's note: The story has been updated with the correct percentage of retention in the ongoing phase 2 extension trial.