What FDA’s Remibrutinib Approval Reveals About the Future of BTK Inhibitors

For the first time, FDA has approved a Bruton’s tyrosine kinase inhibitor (BTKi) for chronic spontaneous urticaria (CSU), giving the green light to Novartis’ twice-daily oral treatment remibrutinib (brand name Rhapsido) (1). The approval, announced by Novartis on Sept. 30, 2025, was granted for adult patients with CSU who remain symptomatic despite H1 antihistamine treatment.

What is CSU and what are the symptoms?

According to information provided by Novartis, CSU is a mast cell-driven condition that is believed to be brought on by immune dysregulation, with patients’ immune systems becoming activated through either allergic or autoimmune pathways (1). When this happens, immune cells, such as mast cells and basophils, activate the BTK protein; although this process is not fully understood, it can ultimately result in a release of histamine or other, proinflammatory mediators that cause red, swollen, and/or itchy hives.

Onset of symptoms like these hives are often unpredictable in patients with CSU, Novartis said, recurring for six weeks or more with no warning, making diagnosis difficult—sometimes taking up to 24 months (1). Patients report CSU symptoms negatively affecting their sleep, work, and mental health.

Even after first-line antihistamine treatment, more than half of patients still exhibit symptoms, including after being administered higher doses (1). For those who do not respond to antihistamine treatment, injectable treatments do exist, but Novartis said fewer than 20% of eligible patients receive them.

What’s the larger implication of the remibrutinib approval for the industry?

FDA’s approval of remibrutinib may represent a new phase in the application of BTK inhibitors beyond hematologic malignancies. While BTK inhibitors have become a mainstay in oncology, their expansion into immunology demonstrates the versatility of the drug class and underscores a broader trend of repositioning targeted therapies to address inflammatory and autoimmune conditions. For drug developers, this approval highlights the regulatory willingness to consider well-established mechanisms of action in new therapeutic areas when the unmet need is clearly defined.

The decision also stands to set a precedent for competition in the CSU space, which has historically relied heavily on injectable biologics. The availability of a twice-daily oral treatment offers a more convenient alternative, potentially shifting prescribing patterns and influencing payer considerations. This shift could encourage other manufacturers to accelerate development of small-molecule therapies in areas traditionally dominated by biologics, further blurring the lines between the two modalities.

For the bio/pharmaceutical industry more broadly, the approval reflects the growing emphasis on precision immunology and the push toward diversifying portfolios across therapeutic classes. As more companies pursue BTK inhibitors for non-oncologic conditions, the long-term impact will likely extend beyond CSU, shaping investment strategies, clinical trial designs, and regulatory pathways for next-generation targeted therapies.

Have other CSU treatments or BTK inhibitors been approved recently?

In March 2025, FDA approved Celltrion’s Omlyclo (omalizumab-igec) as the first interchangeable biosimilar to Genentech and Novartis’ Xolair (omalizumab), both treatments being indicated for a number of conditions, including CSU in those aged 12 and older whose hives have continued uncontrolled by H1 antihistamine treatment (2).

Meanwhile, two BTK inhibitors have been advanced by the European Medicines Agency (EMA) in 2025. In February, EMA’s Committee for Medicinal Products for Human Use gave a positive opinion to Eli Lilly and Company’s Jaypirca (pirtobrutinib), a non-covalent or reversible BTK inhibitor, for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia previously treated with a BTK inhibitor (3).

Then, in August 2025, EMA granted orphan drug designation to rilzabrutinib, an investigational, oral BTK inhibitor from Sanofi, for the treatment of IgG4-related disease (4).

What other moves is Novartis making?

On Sept. 29, 2025, Novartis announced the initiation of a tender offer to acquire Tourmaline Bio, advancing a previously announced merger plan. In parallel, Novartis also said a direct-to-patient platform would launch in the United States Nov. 1, 2025, providing secukinumab (brand name Cosentyx)—Novartis’ top-selling biologic in the US, approved to treat psoriasis, psoriatic arthritis, hidradenitis suppurativa, and other immune-mediated inflammatory diseases—at a 55% discount off list price for cash-paying patients (5).

Anecdotally, Novartis was one of 17 pharmaceutical companies to receive letters from the White House on July 31, 2025, outlining the step-by-step process US President Donald Trump said the companies must take to lower prescription drug prices in the US to the lowest price offered among other developed nations, a strategy known as the most-favored-nation price (6). Pfizer was the first of these companies to announce an agreement with the White House, on Sept. 30, 2025 (7).

Earlier in September 2025, Monte Rosa Therapeutics announced its second collaboration with Novartis focused on developing novel degraders for immune-mediated diseases, building on the companies’ initial 2024 licensing agreement for vav guanine nucleotide exchange factor 1 degraders, including MRT-6160, a candidate advancing toward multiple Phase II studies (8).

References

1. Novartis. Novartis Receives FDA Approval for Rhapsido (remibrutinib), the Only Oral, Targeted BTKi Treatment for Chronic Spontaneous Urticaria (CSU). Press Release. Sept. 30, 2025.
2. Lavery, P. FDA Approves Celltrion’s Omalizumab Biosimilar. BioPharmInternational.com, March 13, 2025.
3. Eli Lilly and Company. Lilly's Jaypirca (pirtobrutinib) Recommended by CHMP for Approval in the European Union for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Previously Treated with a BTK Inhibitor. Press Release. Feb. 28, 2025.
4. Sanofi. Sanofi’s Rilzabrutinib Earns Orphan Designation in the EU for IgG4-Related Disease. Press Release. Aug. 14, 2025.
5. Mirasol, F. Novartis Advances Pipeline and Redefines Distribution with Tourmaline Acquisition and DTP Platform. BioPharmInternational.com, Sept. 29, 2025.
6. Lavery, P. Trump Sends Letters to 17 Leading Pharma Companies Outlining Most-Favored-Nation Drug Pricing Protocol. PharmTech.com, Aug. 1, 2025.
7. Lavery, P. Pfizer Reaches First Agreement with White House on MFN Pricing; Who Will Be Next? PharmTech.com, Sept. 30, 2025.
8. Mirasol, F. Monte Rosa and Novartis Partner to Target Undruggable Immunology Pathways with Degraders. BioPharmInternational.com, Sept. 15, 2025.