Atuzabrutinib

Pictured: Scientist in lab/Courtesy, Getty Images Reptile8488/Getty Images The companies said in first-quarter earnings calls that they want to restructure R&D, cut costs and shift away from high-risk drug development to focus areas. Pictured: Scientist in lab/Courtesy, Getty Images The first-quarter 2023 biopharma earnings season saw a clutch of leading drug developers cull pipeline programs, with Biogen , Novartis , and Sanofi among the companies to discard clinical-phase candidates in recent updates. The companies are looking to restructure research and development, cut costs, and shift from high-risk drug development to focus areas. Below is a round-up of what changed and why at the three companies in their reporting of first-quarter results. Biogen Christopher Viehbacher used the first quarter to continue the pipeline pivot he has overseen since becoming CEO of Biogen in November 2022. The changes include the termination of the development of BIIB093 for the prevention and treatment of severe cerebral edema in large hemispheric infarction, one of the most severe types of ischemic stroke. Talking to investors on a quarterly results conference call, Biogen’s head of development, Priya Singhal, attributed the action to “operational challenges and strategic considerations.” Biogen filed to run a Phase III trial of the candidate in August 2016. The study started two years later, 18 months behind schedule, and the targeted completion date has slipped twice since then. Biogen also decided to pause the start of a Phase IIb clinical trial of BIIB131 in acute ischemic stroke. At the same time, it weighs up on whether to run the study and has stopped the development of BIIB132 in spinocerebellar ataxia type 3. The changes follow disclosures that Biogen is reconsidering its approach to gene therapy and exiting ophthalmology research. Viehbacher told investors that changes are not just an effort to reduce costs. Instead, Biogen is stopping investing in some programs to “focus resources on those assets that we think are most promising,” such as the tau antisense oligonucleotide BIIB080 in Alzheimer’s disease. “We’ve actually already allocated more resources to accelerate this program,” Viehbacher said. Novartis Novartis followed through on its promise to narrow its focus in the first quarter by disclosing the removal of 10% of its pipeline programs. With the Swiss drug developer focusing on a few therapeutic areas and technology platforms, it is discarding or out-licensing candidates that fall outside its attention areas. “We systematically looked at the pipeline to identify projects that were outside the scope of those core therapeutic areas or, in the case of oncology, were addressing tumors that are no longer priority tumors for the company. We wanted to stop those projects,” Novartis CEO Vas Narasimhan told investors on a first-quarter conference call. “We have identified five tumor types we’re particularly interested in, and we’re trying to focus our energy there.” Narasimhan described Novartis’ actions as a “cleanup” of its portfolio and emphasized that its focus on “high-value medicines” remains on track. Asked specifically about oncology, he said the emphasis is on higher-quality projects in the portfolio going forward. Sanofi Sanofi, where Viehbacher was CEO until 2014, disclosed pipeline cuts days after Biogen. The most advanced asset affected by the changes was atuzabrutinib, a topical BTK inhibitor Sanofi acquired in its $3.7 billion takeover of Principia Biopharma. Sanofi blamed removing the drug candidate from its phase II pipeline on “efficacy and sub-optimal pharmacokinetics.” The French drugmaker disclosed the action alongside news of the end of the development of anti-TNFa/IL-6 nanobody SAR444419, a candidate based on the platform it acquired through the Ablynx buyout in 2018. The inflammatory disease prospect was in phase I development before Sanofi stopped work “based on the benefit/risk assessment.” Despite the setbacks, Sanofi CEO Paul Hudson told investors the company is “increasingly confident” in its ability to “fuel our next chapter of growth with innovative compounds and new launches from our pipeline.” Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn .

The action adds to worries that Sanofi’s bet on Principia will fall flat. 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.