Sanofi already has one oral drug for multiple sclerosis in its portfolio, but has snapped up another from Principia Biopharma in a deal that gives the Californian biotech a $40m upfront payment.
The focus of the deal is PRN2246, a Bruton’s tyrosine kinase (BTK) inhibitor that is in phase I clinical development for a number of central nervous system diseases. The BTK inhibitor has been specifically designed to cross the blood-brain barrier, a physiological obstacle that is designed to protect the brain from chemicals and often poses a challenge for CNS drug development. Other BTK inhibitors in development do not have this quality, according to Principia.
“BTK inhibition impacts multiple immune cell signalling pathways relevant in both the periphery and within the CNS, holding promise for the treatment of neurologic diseases,” it says.
Along with the upfront payment, Sanofi is pledging milestones payments of up to $765m plus royalties on sales if the PRN2246 makes it through to market. In return it gets an exclusive worldwide license to the candidate for MS and potentially other diseases, although Principia can choose to help fund phase III trials in return for higher royalties or a profit-sharing arrangement.
Sanofi ‘s established oral MS therapy is Aubagio (teriflunomide), which got off to a slow start after its launch in 2012 in the face of competition from rival drugs from Biogen and Novartis but has grown steadily in the intervening years. In the first nine months of 2017 it brought in €1.15bn ($1.34bn) for the French big pharma group.
With a 27% growth it is still one of Sanofi’s most important products, but is still lagging behind Biogen’s market-leading Tecfidera (dimethyl fumarate) which brought in almost $2.5bn in the same period, as well as Novartis’ Gilenya (fingolimod) which was only a little behind with $2.36bn in revenues.
The three established players in the oral MS therapy category are also about to see additional competition from new entrant Merck KGaA, which bagged EU approval for Mavenclad (cladribine) in August. And an even bigger threat is looming in the shape of Celgene’s ozanimod, a once-daily oral therapy that GBI Research has predicted could make rapid headway thanks to a benign safety profile.
“The agreement allows Principia to maximize the BTK opportunity in neurology with a strong partner for PRN2246, while focusing internal resources on our lead BTK inhibitor in another therapeutic area,” said Principia’s chief executive Martin Babler.
Principa’s lead BTK drug is PRN1008, which is in phase II testing for autoimmune disease pemphigus vulgaris. BTK is best known as the target for Johnson/AbbVie’s big-selling blood cancer therapy Imbruvica (ibrutinib) and AstraZeneca’s recently-approved rival Calquence (acalabrutinib).