Sanofi’s $3.7 billion Principia Biopharma buyout has delivered a phase 3 victory. The BTK inhibitor moved the needle in a clotting disorder, clearing Sanofi to file for approval of a “multi-indication blockbuster” that it predicts (PDF) could contribute to more than 10 billion euros ($11 billion) of drug launch sales.
The candidate, rilzabrutinib, is an oral, reversible BTK inhibitor that was already in phase 3 when Sanofi bought Principia. Researchers designed the candidate to have a lower risk of off-target effects and to be active at lower levels of systemic exposure than other BTK inhibitors, attributes that could support use outside of the B-cell mediated diseases typically targeted by the drug class.
Rilzabrutinib suffered a setback in 2021, when it flunked a phase 3 pemphigus trial, and missed the mark in a phase 2 atopic dermatitis trial last year. Yet, successes elsewhere have encouraged Sanofi to gear up for phase 3 trials in other indications as it enters a crucial run of readouts from rilzabrutinib studies.
The first readout was positive, with Sanofi reporting the LUNA 3 trial hit the primary endpoint of durable platelet response in adults with persistent or chronic immune thrombocytopenia (ITP). Sanofi linked rilzabrutinib to a higher rate of durable platelet response than placebo.
All participants had been failed by other therapies and had taken a median of four other ITP treatments. The median baseline platelet count was 15,000/μL, putting patients 90% below the bottom end of the normal range. Because they lack platelets, people with ITP can have bleeding that is hard to stop, leading to spots under the skin, nosebleeds and tiredness.
Sanofi is yet to share data from the trial but discussed results beyond the primary endpoint at a high level. Rilzabrutinib delivered positive results on key secondary endpoints, Sanofi said, and had a safety profile that was consistent with earlier studies. There is a long and ongoing history of safety issues linked to BTK inhibitors but rilzabrutinib is designed to stand apart from the pack in that regard.
Encouraged by the phase 3 data, Sanofi plans to file for approval of rilzabrutinib in Europe and the U.S. in ITP by the end of the year. The filing forms part of a busy near-term roadmap for the molecule. Sanofi is set to report data from a phase 2 asthma study in the first half of the year, with midstage readouts in IgG4-related disease and warm autoimmune hemolytic anemia set to follow by the end of 2024.
The French drugmaker is also setting the stage for another round of readouts, with phase 3 clinical trials in prurigo nodularis and chronic spontaneous urticaria scheduled to start in the second half of 2024. The activity informs Sanofi’s belief that rilzabrutinib is a multi-indication blockbuster that could treat more than 3 million patients with a range of diseases.