Amlitelimab

Welcome back to Endpoints Weekly! A programming note: We won’t be sending our usual newsletters on Monday, Feb. 16. Our team will be off for Presidents’ Day. Our reporters closely followed several big updates this week, including Moderna’s response after it received a refusal-to-file letter over its flu vaccine application and Paul Hudson’s exit from Sanofi. Senior editor Max Gelman also dug into what makes clinical trials so costly. And our team reported on readouts for AstraZeneca’s obesity pill and the launch of a head-to-head CAR-T trial. Enjoy the weekend — we’ll be back on Tuesday! — Nicole DeFeudis The FDA refused to review Moderna’s flu vaccine application, in a decision that the company is describing as a shifting of standards for its pivotal trial. The Phase 3 trial tested Moderna’s mRNA-based flu shot against a standard flu dose in adults 50 and older. But in a refusal-to-file letter, the agency criticized Moderna for not using the “best-available standard of care” in the comparison group. Typically, patients 65 and older are advised to get a higher or enhanced dose. Moderna took the debate public on Tuesday, publishing the refusal-to-file letter signed by vaccines and biologics chief Vinay Prasad. In the letter, Prasad wrote that the decision was “consistent with FDA’s advice given to you prior to your study.” In a news release, Moderna said the agency recommended in 2024 that Moderna use a higher-dose flu vaccine in adults 65 and older, but also agreed at the time that “it would be acceptable to use a licensed standard-dose influenza vaccine as the comparator in your Phase 3 study.” “We thought it was pretty clear that it was acceptable, and even agreed it was an acceptable approach in writing,” Moderna president Stephen Hoge said in a Tuesday interview. The debate was further complicated by reports from Endpoints News and others that Prasad overruled the review team and head of the vaccine group as part of the regulator’s refusal to review the application. On Wednesday, a senior agency official told reporters it was “entirely feasible” that Moderna could resubmit the application for adults aged 50 to 64. If approved, the vaccine could be used off-label for the oldest adults, the official said. They also said, “There was a healthy scientific debate on the refuse-to-file.” Moderna has requested a Type A meeting with the FDA to further discuss the application. On its fourth-quarter earnings call Friday, Moderna’s CFO Jamey Mock said it’s “too early to tell” whether the company’s goal of reaching break-even cash flow will be pushed back after the FDA declined to review its flu shot for adults 50 and older. For more discussion, watch our Post-Hoc Live session with the Endpoints reporters who tracked this story. Sanofi’s board elected not to renew Paul Hudson’s director mandate, the company announced this week, ending Hudson’s tenure as CEO . He will be replaced by Merck KGaA’s Belén Garijo, who will start on April 29. Hudson’s last day is Feb. 17, and head of general medicines Olivier Charmeil will take over as interim CEO during the transition. The ouster comes after years of pipeline setbacks for Sanofi. Hudson, who started in his role in September 2019, had attempted to reposition the company as an immunology powerhouse. By acquiring companies like Principia and Kymab, Hudson bet that not only could Sanofi be at the forefront of immunology’s next frontier, but it could also minimize risk from the Dupixent patent cliff in the early 2030s. That strategy ended up being rocky, and Sanofi’s board appeared to have lost patience as the company faced a number of pipeline setbacks. One of the Principia programs was scrapped three years after the acquisition, and another was rejected by the FDA late last year. The centerpiece of the Kymab deal, an anti-OX40L program called amlitelimab, was positioned as a “pipeline-in-a-product,” but reported disappointing data in January despite achieving its primary goal. A new safety concern also cropped up, casting a growing shadow on the mechanism. Despite the change in leadership, reception for Garijo was frosty. Investors are concerned that Garijo doesn’t have a track record of delivering R&D productivity at Merck KGaA, according to analysts who spoke to Endpoints, partly due to pipeline misfires. But some of that criticism may be misplaced. Read more about the challenges Garijo will face here . And be sure to read more about Hudson’s departure, as well as all the other pharma job changes this week, in our weekly Peer Review column here . US clinical trials, particularly in oncology, have become increasingly redundant, inefficient and expensive. In a story this week, senior editor Max Gelman examined why this is the case . A closet full of identical EKG machines, as recounted by Eli Lilly’s head of oncology Jacob Van Naarden, illustrated the issue. Ironically, one of the most commonly cited problems of developing new drugs was the cost of older drugs. Precision oncology has exploded since Herceptin’s approval in 1998, and successful checkpoint inhibitors like Yervoy and Keytruda mean that even before a patient gets a dose of an experimental medicine, trials can cost hundreds of thousands of dollars a year. Other factors only compound the problem. Companies must staff trial sites and manufacture new therapies while contending with American patients’ unwillingness to take experimental medicines and payers’ reluctance to foot the bill. As costs have risen, many big companies — and some smaller biotechs — have turned to China, but it’s not a simple solution. Unfortunately, there’s no silver bullet to fixing this problem. The solution depends on who you ask. Read more from Max here . The Bay Area biotech announced this week that it treated the first patient in a Phase 3 trial that pits its experimental cell therapy ronde-cel against two currently available CAR-T treatments for certain patients with aggressive large B cell lymphoma. Lyell CEO Lynn Seely told Endpoints’ Lei Lei Wu that the company “wanted a randomized, controlled trial so we could have a very fair evaluation” of whether ronde-cel can beat the existing therapies. Lyell, Gilead and Johnson & Johnson are all studying next-generation CAR-T therapies for lymphoma that target two proteins — CD19 and CD20 — typically found at abnormally high levels in cancers, as opposed to CD19 alone. Gilead has outlined plans for a head-to-head Phase 3 trial in which it will go up against its existing therapy, Yescarta. Click here for more details. AstraZeneca added to the obesity pill mania this week when it reported that its oral GLP-1 elecoglipron succeeded in two Phase 2b studies — one for obesity and one for diabetes. Specific data were not announced, but the drugmaker said they would come in June. According to the trial protocol, senior biopharma journalist Elizabeth Cairns says it can be inferred that the drug produced greater weight loss than placebo at the 26-week mark and also allowed more subjects to lose at least 5% of their weight at the same point. AstraZeneca will start Phase 3 trials this year. The UK pharma licensed elecoglipron from the Hong Kong company Eccogene in November 2023. AstraZeneca paid $185 million upfront for the asset. Eccogene is aiming to go public, probably this year. Read more from Elizabeth here . DON’T MISS