Novartis has scored the FDA’s approval for a second BTK inhibitor that’s for a non-cancer indication, teeing off a potential competition with Sanofi down the line.

The FDA has blessed Novartis’ remibrutinib, to be marketed under the brand name Rhapsido, as an oral drug for adult patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamine treatment.

CSU, also known as chronic hives, is a familiar area for Novartis, which has been selling the injectable Xolair together with Roche for the immune disorder in the U.S. since 2014. In April, the FDA also cleared Sanofi and Regeneron’s blockbuster antibody Dupixent to treat CSU.

Rhapsido comes with a novel mechanism of action. As BTK plays an important role in mast cell degranulation and hence the release of histamine that causes hives, as well as in B cell-mediated autoantibody production, inhibiting BTK signaling could tackle both the allergic and autoimmune types of CSU, Victor Bulto, Novartis’ U.S. president, explained in a recent interview with Fierce Pharma.

Despite its availability for over a decade, adoption of Xolair in CSU has been limited mostly to patients who have exhausted all other options, Bulto observed. That’s partly because dermatologists are generally not used to administering injectables, and Xolair carries a black box warning.

For Rhapsido, Novartis is angling the oral med right after antihistamines have stopped working, Bulto said. And the trigger for the search for another treatment option, according to Bulto, is typically when patients can’t sleep right.

By that standard, Novartis estimates the target CSU population in the U.S. is about 400,000, out of about 1.7 million people who live with the disease in the country, Bulto said. Of those target patients, only about 20% are being treated with either Xolair or Dupixent today, leaving a big space for Rhapsido.

Rhapsido proved its worth in CSU through the phase 3 Remix-1 and Remix-2 trials. Among patients with symptomatic CSU despite second-generation antihistamines, Rhapsido showed superiority over placebo in change from baseline in itch, hives and weekly urticaria activity at Week 12. Longer-term data presented last year showed that almost half of patients were completely free of itch and hives at the one-year point. Compared with placebo, significantly more patients treated with Rhapsido achieved well-controlled disease as early as Week 2 and at Week 12.

For a serious disease that can cause debilitating symptoms and unpredictable flares, Rhapsido represents “an exciting new option that has the potential to help a broad range of patients get fast relief,” Mark Lebwohl, M.D., from the Icahn School of Medicine at Mount Sinai and a member of the steering committee for the Remix clinical trial program, said in a Sept. 30 release.

Besides its efficacy in controlling hives and itching that plague CSU patients, Rhapsido “gives patients an oral option that can easily be incorporated into their daily lives,” Giselle Mosnaim, M.D., from the University of Chicago and an investigator of the Remix program, said in a statement.

Rhapsido has demonstrated a safety profile that does not require any lab monitoring, according to Novartis. This feature will give dermatologists confidence to treat resistant patients with the drug rather than referring them to allergists, Bulto noted.

Rhapsido’s approval follows an FDA go-ahead a month ago for Sanofi’s BTK inhibitor Wayrilz in immune thrombocytopenia (ITP). The French pharma has already moved the drug into a phase 3 study in chronic hives following a positive midstage trial readout.

One notable difference between the two BTK inhibitors is that Wayrilz’s binding to BTK is reversible with both noncovalent and covalent binding regions, whereas Rhapsido works by forming irreversible covalent bond with BTK. In cancer treatment, reversible noncovalent BTK inhibitors are generally considered safer than their covalent counterparts.

Novartis has not seen any alarming safety signal with Rhapsido across trials in multiple indications, Bulto said.

Both companies are eager to expand their options into other immunology indications, which underpin Novartis’ multibillion-dollar peak sales estimate for Rhapsido.

The Novartis drug recently showed promise in food allergy in a phase 2 trial, as the Swiss pharma spotlights its potential to become the first oral allergen-agnostic treatment. If successful, food allergy would be a huge opportunity with a patient population of 20 million in the U.S., according to Bulto.

Besides CSU, Novartis expects pivotal readouts for Rhapsido in chronic inducible urticaria and multiple sclerosis in 2026. The drug is also being pushed into phase 3 studies for hidradenitis suppurativa and generalized myasthenia gravis.

For Sanofi, the French drugmaker is also testing Wayrilz in asthma, focal segmental glomerulosclerosis, warm autoimmune hemolytic anemia and IgG4-related disease.

“We want to go to areas where we have the confidence that our scientists, our drug developers, our commercial teams know well,” and Novartis can use that know-how to understand whether its compound can win in the target areas, Bulto said.

Novartis is beefing up its immunology portfolio with the likes of Rhapsido as its Cosentyx, which generated nearly $3.2 billion sales in the first half of 2025, is slated to lose patent protection toward the end of the decade.