Sanofi, after $8B outlay, sees M&A strategy deliver 2 more duds

Sanofi’s first-quarter update (PDF) brought bad news for drug candidates acquired in buyouts worth $8 billion, with the French drugmaker removing Ablynx and Principia Biopharma molecules from its pipeline after getting a look at clinical data.

Ablynx, bought for 3.9 billion euros ($4.3 billion) in 2018, and Principia, acquired for $3.7 billion two years later, are among the bigger bets Sanofi has placed on biotech buyouts in recent years. Reeling from a big setback to its $2.5 billion Synthorx takeover, Sanofi needs its M&A strategy to start delivering, but the first-quarter results brought no relief on that front.

In the update, Sanofi disclosed the discontinuation of trials of the topical BTK inhibitor atuzabrutinib and anti-TNFa/IL-6 nanobody SAR444419. Sanofi added atuzabrutinib in the Principia deal, while SAR444419 is derived from the nanobody platform at the heart of the Ablynx takeover.

Working with Sanofi, Principia took atuzabrutinib into a phase 2a clinical trial in patients with mild to moderate atopic dermatitis in 2021. A look at data from the study, which wrapped up late last year, led Sanofi to stop development “due to efficacy and sub-optimal pharmacokinetics.” 

The action adds to worries that Sanofi’s bet on Principia, which had its knockers at the time, will fall flat. Sanofi stopped developing Principia’s lead candidate in myasthenia gravis earlier this year, citing the level of competition in the indication. Development of the asset, tolebrutinib, is ongoing in multiple sclerosis, but a partial clinical hold, which could stem from a classwide effect, has tempered expectations. 

Sanofi’s presentation made no mention of the partial clinical hold on tolebrutinib, only stating that the first pivotal readout is due around the end of the year. The drugmaker had hoped to resolve the hold by the end of last year, but the situation has dragged on, albeit without stopping Sanofi from dosing existing participants or preventing work toward pivotal data.

In a call with analysts this morning, Sanofi’s Global Head of R&D Dietmar Berger said the Big Pharma is “working closely” with the FDA to address the issues with the U.S. tolebrutinib trial.

“What they're looking for is further understanding of the patient population,” he added. “We have our program ongoing with regards to really close monitoring. We have not seen any new cases of liver toxicity in the same way since we introduced that level of monitoring, which is important to understand.”

“Obviously, the FDA is looking for more data on that and is also looking eventually for benefit-risk information, which we will have at the time when we will read out the study.”

The nanobody culled from the pipeline in the first-quarter update was in phase 1 development. Sanofi saw the candidate as a potential treatment for an inflammatory disease but has stopped work “based on the benefit/risk assessment.” The action comes months after Sanofi punted (PDF) a pair of nanobodies that were in phase 1 in atopic dermatitis and an inflammatory indication because of their clinical profiles.