Principia Biopharma, Inc.

Bolstering Sanofi's immunology and inflammation (I&I) growth aspirations, the FDA on Friday approved the French pharma's Wayrilz (rilzabrutinib) for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The nod lends credence to Sanofi's $3.7-billion purchase of Principia Biopharma to gain the asset in 2020, as Wayrilz now represents a potential key growth driver for its I&I pipeline — an area the drugmaker is increasingly relying on for revenue as it slims down its oncology portfolio. For related analysis, see Vital Signs: Sanofi builds momentum for its I&I bets.An oral BTK inhibitor, Sanofi said Wayrilz can get at the root causes of ITP by targeting different pathways across the immune system."With its differentiated mechanism of action, Wayrilz has the potential to become a treatment of choice for immune thrombocytopenia patients who have not responded to a prior therapy," Brian Foard, Sanofi's head of specialty care, said in a company release. "Its multi-immune modulation approach shows promise in addressing the key drivers of immune thrombocytopenia, which aligns with Sanofi's commitment to adapting and evolving therapeutic solutions to help tackle ongoing unmet patient needs."Durable platelet responseThe approval was based on results from the Phase III LUNA 3 study, which were toplined last April before being shared in more detail at last year's American Society of Hematology (ASH) meeting. The 202-patient study compared twice-daily oral Wayrilz against placebo. The BTK inhibitor met the trial's primary endpoint of durable platelet response, with 23% of patients who received the therapy achieving platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, compared with zero patients in the placebo group. Additionally, Wayrilz reduced the need for rescue therapy by a significant 52% versus placebo, and also led to significant and clinically meaningful improvements in physical fatigue and bleeding. The most common treatment-related adverse events were diarrhoea (23%), nausea (17%), headache (8%) and abdominal pain (6%).Feedback from experts suggest Wayrilz is likely to become a go-to second-line option after thrombopoietin receptor agonists, with the potential to quickly gain traction due to physician familiarity with BTK inhibitors such as Imbruvica (ibrutinib) in blood cancers. However, Sanofi has plenty of competition nipping at its heels from Novartis' BAFF-R antibody ianalumab and several anti-CD38 mAbs. For further analysis, see KOL Views Q&A: Sanofi's rilzabrutinib can contend in ITP but competition fierce and more footsteps approaching.Outside the US, Wayrilz is under regulatory review in the EU and China.

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. 

The FDA approved Sanofi’s BTK inhibitor that the French drugmaker acquired in its $3.7 billion buyout of Principia Biopharma. The company said Friday that the regulators cleared rilzabrutinib in a rare disease called immune thrombocytopenia, or ITP. The drug is branded as Wayrilz. The wholesale acquisition cost for Wayrilz will be $17,500 a month, which is before discounts, rebates or patient assistance programs, a Sanofi spokesperson said. Wayrilz is part of a larger effort at Sanofi to become the leading immunology pharma company. Sanofi has unveiled or acquired a handful of programs targeting immunological conditions in recent years, and the company expects Wayrilz to produce between €2 billion and €5 billion in annual peak sales. So far, Sanofi’s strategy hasn’t always led to success. The company was forced to shelve studies of another drug from Principia called tolebrutinib in 2023 after trials were put on hold . The drug continued to be dogged by safety concerns despite positive efficacy results in a multiple sclerosis trial that read out last year. Tolebrutinib had been Principia’s lead drug at the time Sanofi acquired the company in 2020. Another program called itepekimab underwhelmed in a COPD study earlier this year. And even the path for Wayrilz has been bumpy. The drug failed an atopic dermatitis study in 2023. Sanofi’s immunology pipeline also includes amlitelimab, an OX40L drug from Kymab that’s currently in Phase 3 studies for atopic dermatitis; lunsekimig, an anti-IL-13/TSLP program with a Phase 2 readout in asthma expected next year; and frexalimab, a CD40L-targeting therapy that’s expecting Phase 2 lupus data in the second half of 2026. “Our current and evolving portfolio within immunology and immunoscience more broadly really explores the multifaceted nature of key neurologic nodes within the immune system,” Sanofi CSO Mike Quigley told Endpoints News in an interview ahead of the decision. As for Wayrilz, ITP is a rare autoimmune disorder that leads to low platelet counts and an increased risk of bleeding and bruising. Quigley estimates there are about 100,000 ITP patients in the US. In addition to ITP, Sanofi is continuing to study Wayrilz in asthma, chronic hives, IgG4-related disease and other rare diseases, though these studies are early and no readouts are expected until 2027. Editor’s note: This story was updated to add the drug’s wholesale acquisition cost.