- An experimental drug to treat a rare autoimmune skin disorder failed in a late-stage trial, Sanofi said Thursday, reporting that, when combined with steroids, the oral treatment did not clear lesions better than steroids alone. Called rilzabrutinib, the drug was being tested in patients with pemphigus, which causes skin blistering and can be life-threatening.
- Rilzabrutinib was one of three similar drugs Sanofi acquired with its $3.7 billion buyout of Principia Biopharma in 2020, part of a spate of deals that has seen the French pharma spend tens of billions on biotechs over the past five years. The second drug, called tolebrutinib, is in late-stage studies in multiple sclerosis.
- The two drugs block an enzyme active in immune response, targeting a pathway that has been shown important to treating several types of blood cancer. Sanofi is competing with Merck KGaA and Roche to bring a drug from this class to market in MS.
Known best for its cardiovascular and metabolic drugs, Sanofi has sought to beef up its pipeline by buying biotechs testing experimental drugs in cancer, autoimmune and rare diseases. Since 2018, it has spent nearly $30 billion on acquisitions, according to data from BioPharma Dive, including an $11.6 billion takeout of Bioverativ, the hemophilia-focused spinout of Biogen.
The Principia buyout was a follow-through from a licensing deal Sanofi made on MS candidate tolebrutinib, also called SAR442168. With the acquisition, Sanofi gained access to two other drugs from this class, known as Bruton's tyrosine kinase inhibitors, rilzabrutinib and PRN473.
Eleven BTK inhibitors are in clinical testing in autoimmune disorders, according to Nature Biotechnology, but just two, rilzabrutinib and Gilead and Ono Pharmaceutical's tirabrutinib, were targeting pemphigus. As a drug targeting a rare disease, rilzabrutinib could have commanded a premium price, but with the PEGASUS trial results announced Thursday that outcome is looking less likely.
The trial randomized patients to receive rilzabrutinib or a placebo on top of a small dose of corticosteroid, and measured whether the combination treatment was better at eliminating patients' skin lesions between 29 and 37 weeks of treatment. Sanofi said it missed that endpoint, along with others measuring time to and duration of remission as well as cumulative corticosteroid dose.
The drug might not be shelved just yet, as it is also in a Phase 3 trial for a second disorder, immune thrombocytopenia. The Food and Drug Administration has granted Orphan Drug and Fast Track status in both diseases, providing for expedited review should another trial turn out positive.
The larger prize in the Prinicipia buyout likely was tolebrutinib, which treats a much more common disorder for which patients want more oral options — highly effective drugs like interferon, Tysabri and Ocrevus require injection or infusion.
Sanofi could have challengers in MS, however, as its Phase 3 trials of tolebrutinib are likely to read out on a similar time frame as those of Merck KGaA's evobrutinib and Roche's fenebrutinib, in 2023 and 2024.