Fenebrutinib

Welcome back to Endpoints Weekly. It’s going to be a chilly weekend here in Boston, with low temperatures dipping into the 30s — the perfect weather for a warm cup of tea while recapping another busy week in biopharma. If you haven’t already, be sure to read the Endpoints team’s exclusive on how Pfizer closed its deal with Metsera. We also have a feature from Max Gelman on how competition is stacking up in the PD-(L)1xVEGF space, details on Richard Pazdur’s appointment to CDER, some positive results for Roche’s BTK inhibitor, and the story behind a new VC firm hunting for the next big advances in obesity treatment. We’ll be back on Monday. Until then, stay warm! — Nicole DeFeudis 💇‍♂️Pfizer completed its up to $10 billion acquisition of the obesity biotech Metsera this week, ending a high-stakes bidding war between Pfizer and Novo Nordisk. Last week, we reported that Metsera had accepted Pfizer’s offer after the FTC warned the biotech that Novo’s bid was risky under US antitrust law. But you can see exactly how the final deal unfolded in this exclusive by Endpoints’ Elizabeth Cairns, Kyle LaHucik and Drew Armstrong — including how Metsera’s co-founder Paul Berns was in the middle of a haircut when he was alerted that Novo was submitting its surprise offer. The deal gives Pfizer a fresh chance in obesity after the company dropped its obesity pill danuglipron in April. Novo fought hard for Metsera, as it looks to maintain a leading stake in the obesity market. But even though Pfizer won the battle, all eyes will be on how the experimental drugs it acquired perform in trials. Stay tuned. 🏎️ Drugmakers in the PD-(L)1xVEGF space are revving their engines, Endpoints’ Max Gelman reported this week. While much of the focus has been on Summit Therapeutics and its lead drug ivonescimab, two other rival teams have recently detailed their clinical development plans. Check out Max’s in-depth look at the competition here. One of the challengers is Pfizer and 3SBio, which inked a licensing deal for a PD-1xVEGF bispecific called SSGJ-707, or PF’4404, earlier this year. Pfizer said on Monday that among other trials, it has plans for a Phase 3 study in first-line metastatic colorectal cancer and a Phase 3 non-small cell lung cancer study evaluating both squamous and non-squamous tumors. Bristol Myers Squibb and BioNTech are also in the running. They teamed up this year to advance a PD-L1xVEGF program that BioNTech got in its Biotheus acquisition. Bristol Myers outlined plans for five mid- and late-stage studies during an earnings call last month, and BioNTech said this week that it’s also looking at studies in pancreatic cancer, ovarian cancer and glioblastoma. Both companies intend to look at combinations within their respective pipelines, Max reported. Despite all the momentum, the race could take a while to play out as Summit plans to launch more studies and we wait for key data from Pfizer and BMS. Longtime cancer chief Richard Pazdur was appointed to lead the Center for Drug Evaluation and Research, just over a week after former director George Tidmarsh’s sudden resignation. Pazdur has 26 years of experience at the agency and is the founding director of the FDA’s Oncology Center of Excellence. During his time at the FDA, he has been focused on speeding up the development of new cancer therapies. Pazdur vs. Prasad: Current CBER Director Vinay Prasad previously criticized Pazdur in social media posts before Prasad joined the FDA. Endpoints’ Zachary Brennan analyzed the complex dynamic and the events that led to Pazdur’s appointment here. 💵Two former executives of Lilly’s diabetes unit have launched a venture capital firm called 501 Ventures, and they’re looking for the next approaches to obesity treatment. The firm will fund science for next-generation metabolic health medicines. Its founders, Enrique Conterno and Meg Powell, wouldn’t disclose the amount of capital they’re working with so far. But Powell said they’ll court pharma companies to help support the fund. Kyle LaHucik reported the details from this year’s ObesityWeek conference in Atlanta. Read more here . Roche reported positive results from two separate Phase 3 trials that tested fenebrutinib  in relapsing multiple sclerosis and primary progressive multiple sclerosis. Roche hasn’t shared the detailed results, but CMO Levi Garraway described the wins as “unprecedented.” Roche said it will wait for data from a second Phase 3 RMS trial before finalizing regulatory filing plans.

Genentech, a member of the Roche Group, has announced positive results from the first of two phase 3 trials investigating fenebrutinib, the first and only Bruton’s tyrosine kinase (BTK) inhibitor in development for the treatment of relapsing multiple sclerosis (RMS). Multiple sclerosis (MS) is a chronic neurological condition affecting more than 2.9 million people globally. Approximately 85% of patients are diagnosed with RMS, which is characterised by relapses and progressive disability over time. The remaining 15% have primary progressive multiple sclerosis (PPMS), a form marked by continuous worsening of symptoms without relapses or remissions. Currently, the only treatment approved by the US Food and Drug Administration (FDA) for PPMS is Ocrevus (ocrelizumab). Fenebrutinib is an investigational, oral BTK inhibitor that targets both B cells and microglia in the immune system. This dual mechanism of action is designed to address key drivers of MS pathology: B-cell inhibition helps to control the acute inflammation responsible for relapses, while targeting microglia within the central nervous system may limit chronic damage and slow long-term disability progression. According to Genentech, fenebrutinib’s high potency, selectivity and reversibility are driven by its non-covalent binding properties, distinguishing it from other treatments currently in development. Results from the randomised, double-blind, double-dummy, parallel-group FENhance 2 study showed that fenebrutinib met its primary endpoint, significantly reducing the annualised relapse rate (ARR) in patients with RMS compared with teriflunomide over 96 weeks of treatment. Results from FENhance 1, the second phase 3 trial in the RMS programme, are expected in the first half of 2026. In addition, the phase 3 FENtrepid study, which evaluated fenebrutinib versus Ocrevus in patients with PPMS, also met its primary endpoint. Fenebrutinib demonstrated non-inferiority to Ocrevus in delaying the onset of composite confirmed disability progression over the treatment period. “Fenebrutinib substantially reduced the number of relapses in RMS and slowed disability progression in PPMS. These unprecedented results suggest that fenebrutinib could potentially become a best-in-disease medicine as the first high-efficacy, oral treatment for people with RMS or PPMS,” said Levi Garraway, Genentech’s chief medical officer and head of Global Product Development. “Therefore, these pivotal results for fenebrutinib may offer new hope for people living with MS, and they reaffirm our enduring commitment to the MS community.”