Tolebrutinib

Sanofi has hailed rilzabrutinib's potential as a “multi-indication blockbuster” that could deliver 2 billion euros to 5 billion euros at its sales peak. While Sanofi originally had its eye on tolebrutinib when it purchased its partner Principia Biopharma for $3.7 billion five years ago, another one of the Bruton tyrosine kinase (BTK) inhibitors inherited from the biotech has made it across the FDA finish line first.The drug rilzabrutinib, which is now approved as Wayrilz in immune thrombocytopenia (ITP), has been hailed (PDF) by Sanofi as a potential “multi-indication blockbuster” that could deliver 2 billion euros to 5 billion euros at its sales peak. The FDA’s approval Friday specifically clears Wayrilz for use in adults with persistent or chronic ITP who haven't responded to prior therapy. The regulatory endorsement marks the first approval for a BTK inhibitor to treat ITP in the U.S., where the condition is estimated to affect around 100,000 people, Mike Quigley, Ph.D., Sanofi’s chief scientific officer and global head of research, said in an interview with Fierce.According to a Friday approval announcement, Sanofi believes there are about 25,000 patients who could specifically benefit from the new medication in the U.S. ITP is an autoimmune disorder in which low levels of platelets—the cells that allow blood to clot—can lead patients to bruise easily, start bleeding without cause and bleed more than those without ITP.To holistically treat ITP, a drug must attack the disease on three fronts, Quigley said, singling out autoantibody production by B cells, FC gamma receptor biology implicated in the body’s immune responses and inflammation. Sanofi believes that BTK proteins form a “key node that sort of permeates all three components of that pathophysiology,” Quigley explained. By targeting BTK with Wayrilz, the French pharma believes it can address ITP across all three of those axes.In contrast, most standard treatments for ITP focus solely on raising patients’ platelet counts, targeting a symptom rather than the underlying cause of the disease, Quigley pointed out.Many patients with the clotting disease receive steroids or thrombopoietin receptor agonists, such as Amgen’s Nplate or Novartis’ Promacta. Roche’s Rituxan is also used off-label to treat the condition in the U.S., though the antibody comes with some trade-offs when deployed against ITP. At the end of the day, ITP is “an unpredictable disease” that is “difficult to treat,” Quigley said.“By our accounts, more than 60% of patients worry about sudden changes in platelet counts,” Quigley said, describing a sense of "helplessness that these patients feel in the context of really unregulatable disease pathophysiology.”In turn, Sanofi is confident that Wayrilz, with its novel mechanism of action, will have a major role to play in subsequent ITP treatment, he said.The FDA green light was informed by Sanofi’s late-stage Luna 3 trial, in which Wayrilz helped raise and sustain platelet levels in 23% of ITP patients at 25 weeks, compared to none in the study’s control arm.The drug also helped patients achieve first platelet responses quicker than placebo, and those responses were longer-lasting, too. The time to first platelet response in the Wayrilz arm of the study landed at 36 days and was "not reached" in the control cohort, according to Sanofi's approval announcement.  Wayrilz also helped patients chart improvements in areas like physical fatigue and bleeding, as measured by the Immune Thrombocytopenic Purpura-Patient Assessment Questionnaire and the ITP Bleeding Scale.The drug’s safety profile was largely on par with the results observed in the trial’s placebo cohort, though patients on Wayrilz were more likely to experience side effects like low-grade diarrhea, nausea, headache and abdominal pain.Sanofi did not disclose pricing plans for the drug in its press release, but it noted that patients will be able to seek financial assistance, navigate insurance coverage and receive other materials for Wayrilz through its HemAssist patient support program. Rilzabrutinib was not the main draw for Sanofi when it moved to acquire the drug’s original developer, Principia, back in 2020. At the time, the company was all in on tolebrutinib—another BTK inhibitor that Sanofi had been developing in partnership with Principia as a potential treatment for multiple sclerosis (MS).But, after reviewing mixed MS data from the asset in 2024, Sanofi in January nixed further development of tolebrutinib in that indication. Sanofi has said it still plans to pursue approval of the drug in another setting.Meanwhile, Sanofi figures rilzabrutinib still has several more arrows in its quiver. Last February, Sanofi elected to move rilzabrutinib into a phase 3 study in chronic hives after the BTK inhibitor posted a win in a midstage chronic spontaneous urticaria study.The French drugmaker is also testing the treatment in asthma, focal segmental glomerulosclerosis, warm autoimmune hemolytic anemia and IgG4-related disease, where rilzabrutinib recently picked up an EU orphan designation.  Outside the U.S., Wayrilz already boasts an ITP approval in the United Arab Emirates, where it was cleared for the treatment of the bleeding disorder in June. Regulators in China and the EU are reviewing the drug for approval in ITP, as well.