Rhapsido soon to be launched in Korea

Approval expected in the first half of this year… first BTK inhibitor for chronic spontaneous urticaria (CSU) nears authorization

Company accelerates indication expansion across autoimmune diseases … competition among follow-on drugs intensifies

A shift in the treatment landscape for chronic spontaneous urticaria (CSU) is imminent. With Novartis positioning an oral BTK inhibitor as a successor to Xolair, competition over treatment options for antihistamine-refractory patients is entering a new phase.

Novartis’s Rhapsido (remibrutinib)

According to industry sources on the 28th, Novartis Korea has recently completed its regulatory submission for Rhapsido (remibrutinib). Approval is expected within the first half of this year.

Rhapsido is an oral targeted therapy that inhibits Bruton’s tyrosine kinase (BTK), a key pathway in the pathophysiology of CSU, thereby blocking the release of histamine and inflammatory mediators. The drug was approved in the United States last September for the treatment of adult CSU patients whose symptoms persist despite second-generation H1 antihistamines.

One of Rhapsido’s most notable features is its oral formulation, taken twice daily. Until now, treatment options for patients unresponsive to first-line antihistamines have been largely limited to the injectable biologic Xolair (omalizumab). The arrival of Rapsido opens a new option, an oral targeted therapy.

According to the Phase III REMIX-1·2 clinical trial results, which formed the basis for its U.S. FDA approval, Rhapsido demonstrated superiority over placebo in improving itch severity (ISS7), hive severity (HSS7), and total urticaria activity score (UAS7) starting from Week 2. Approximately one-third of patients achieved complete remission (defined as zero itch and zero hives) by Week 12.

In terms of safety, the drug showed a favorable profile, being stable enough not to require laboratory monitoring. Common adverse events were mild and included nasopharyngitis, headache, and abdominal pain.

Following the US approval, Novartis has submitted Rhapsido for approval in major markets, including the EU, Japan, and China, where it has received priority review status. With formal submission completed in Korea as well, the entry of the first oral targeted therapy for CSU is imminent.

Beyond CSU, Novartis is also expanding clinical development of Rhapsido across a range of immune-mediated diseases, including chronic inducible urticaria (CIndU), hidradenitis suppurativa (HS), food allergy, and multiple sclerosis.

BTK inhibitors emerge as a successor to biologics in CSU

Competition in the CSU treatment market is rapidly intensifying around BTK inhibitors.

BTK inhibition was first established in hematologic malignancies such as B-cell lymphomas and leukemia. Starting with the first-generation agent Janssen’s Imbruvica (ibrutinib), second-generation drugs BeiGene’s Brukinsa (zanubrutinib) and AstraZeneca’s Calquence (acalabrutinib), and third-generation Lilly’s Jaypirca (pirtobrutinib), have rapidly expanded their market share as later entrants.

With the mechanistic advantages of BTK inhibition having also been confirmed in autoimmune diseases, later entrants are increasingly targeting these indications in drug development.

Sanofi’s Wayrilz

Notably, Sanofi is strengthening its BTK inhibitor lineup in addition to its IL-4/13 inhibitor Dupixent (dupilumab).

In September last year, Sanofi received US approval for the BTK inhibitor Wayrilz (rilzabrutinib) for immune thrombocytopenia (ITP). The drug has now advanced into Phase III trials for chronic inducible urticaria(CIU) and CSU.

While Rhapsido achieves sustained BTK inhibition through irreversible binding, Wayrilz employs a hybrid mechanism combining reversible and irreversible binding.

Sanofi is also developing another BTK inhibitor, tolebrutinib. However, development has recently been put to a stop after the FDA issued a Complete Response Letter (CRL).

This treatment had garnered expectations for its mechanism of action, which selectively suppresses the immune response in multiple sclerosis by regulating B lymphocytes and disease-associated microglia. However, the requirement for additional data has rendered the approval timeline uncertain.