Update (August 21, 2020): For a better understanding of how the BTK pathway compares to other drug targets in the treatment of MS, Xtalks contacted the National MS Society for comment.
“While we have a number of MS treatments today, we still need more highly effective and safe treatments,” said Tim Coetzee, PhD, chief Advocacy Services and research officer, National MS Society. “The BTK pathway is a promising area, and we are excited to see the development of BTK inhibitor drugs as possible treatments for MS.”
Originally published on August 20, 2020:
Looking to bolster its autoimmune portfolio, Sanofi has announced it will be acquiring San Francisco-based Principia Biopharma in a deal valued at $3.68 billion. This all-cash deal will see Sanofi paying $100 per share with unanimous approval from both Boards of Directors.
The main attraction for Sanofi was Principia’s portfolio of Bruton tyrosine kinase (BTK) inhibitors, one of which is being developed to treat multiple sclerosis (MS). In a Phase IIb trial, BTK inhibitor ‘168 — which is being co-developed with Sanofi — decreased severe central nervous system damage (known as T1-hyperintense lesions) by 85 percent, when compared to a placebo. Gadolinium (Gd) enhancement — a contrast agent that accumulates in tissues when the blood-brain barrier is compromised due to inflammation — was used to visualize the lesions.
Since BTK is involved in signal transduction in innate and adaptive cells of the immune system, inhibiting its action could help reduce inflammation and tissue damage associated with autoimmune diseases like MS.
BTK inhibitor ‘168 is now entering Phase III trials with the first patient having been enrolled in June. Two other BTK inhibitors — a rare disease drug (rilzabrutinib) and a more general topical agent (PRN473) — were also highlighted as key assets to be taken over by Sanofi as part of the acquisition.
In a statement about the acquisition, Paul Hudson, CEO of Sanofi, said, “The addition of multiple BTK inhibitors to our pipeline demonstrates our commitment to strategic product acquisitions in our priority therapeutic areas. Full ownership of our brain-penetrant BTK inhibitor ‘168 removes complexities for this priority development program and simplifies future commercialization.”
Hudson announced in December that the French pharma giant would be refining the company’s drug development focus to prioritize its specialty care business, with immunology, oncology and rare diseases being top-of-mind. Stepping away from its cardiovascular and diabetes research, Hudson touted the potential of Sanofi’s Dupixent, an antibody drug approved to treat asthma and atopic dermatitis, saying, “Dupixent has the chance to be one of the most successful medicines in the history of the industry,” in a media call.
Sanofi kicked off its new innovation strategy by acquiring immune-oncology and autoimmune-focused biotech company Synthorx for $2.5 billion in December.
Principia’s proprietary Tailored Covalency platform is touted as the company’s biggest asset in developing its BTK inhibitor franchise. With the goal of limiting off-target effects, the platform is capable of generating small molecule inhibitor drugs with both reversible and irreversible covalent bonds.
Sanofi has been collaborating with Principia since 2017 when the former was granted an exclusive license to develop and commercialize BTK inhibitor ‘168. While the drug is currently being tested in MS, Sanofi also has the option of exploring it in additional indications involving other central nervous system diseases.
“Both ‘168 and rilzabrutinib have ‘pipeline in a product’ potential and we look forward to unlocking their full treatment benefits across an array of diseases,” said Dr. John Reed, global head of research & development at Sanofi.
The deal is expected to be completed by the end of this year.