Vepdegestrant

Welcome back to Endpoints Weekly. Our reporters tracked a flurry of deals and data readouts this week, plus updates on the Trump administration’s health agency picks. Let’s dive in. The Trump administration pulled its nomination for CDC candidate Dave Weldon hours before he was set to appear before the Senate HELP committee on Thursday. The move came as a surprise following what’s been a relatively easy path for other healthcare appointments. Endpoints’ Max Bayer has the details below. Keep reading for a summary of this week’s deals, including Roche and Zealand Pharma’s massive obesity partnership and Bristol Myers Squibb’s acquisition of 2seventy bio. And Elizabeth Cairns has the latest on Pfizer and Arvinas’ breast cancer candidate that extended progression-free survival in certain patients in a Phase 3 trial, but not in the overall population. The companies still plan to file for approval, she reported. Thanks for reading, and have a great weekend! — Nicole DeFeudis 🏛️The Trump administration pulled its nomination for Dave Weldon to lead the CDC on Thursday, hours before his Senate confirmation hearing was scheduled to begin. Weldon, a former Florida congressman, has been sympathetic to concerns about vaccines in the past and was seen as an ally of HHS Secretary Robert F. Kennedy, Jr.’s push to reopen long-settled questions about vaccine safety. The debunked link between vaccines and autism came up several times during the confirmation hearings for Kennedy, as well as for Trump’s NIH and FDA nominees. Two other healthcare nominees are advancing to the full Senate: FDA nominee Marty Makary and NIH nominee Jay Bhattacharya. The Senate HELP committee voted 14-9 in favor of Makary, and 12-11 for Bhattacharya. Mehmet Oz, Trump’s pick to lead CMS, sailed through a Senate confirmation hearing on Friday. The former surgeon and TV personality was questioned about the high cost of healthcare, potential cuts to Medicaid and more. Most of his responses seemed to satisfy legislators. When asked whether he would continue to defend Medicare drug price negotiations under the IRA, Oz responded: “It’s the law. I’m going to defend it and use it.” Meanwhile, the Trump administration must reinstate probationary government employees that it fired without proper notice, according to a court order. A Maryland federal judge granted a temporary restraining order against the government in a legal challenge brought by 20 states over mass layoffs. The order applies to over a dozen federal agencies, including HHS, that were named defendants in the suit. It restores the status quo for 14 days while the court considers a longer injunction. 📉 Pfizer and Arvinas are partnered on protein degrader technology that is aiming to change the treatment paradigm of certain cancers. But the pair ran into a stumbling block this week when they reported that their vepdegestrant program did not extend progression-free survival rates in the overall population of a Phase 3 breast cancer study. Arvinas’ stock price fell more than 50% on the news. The trial was considered the first big test of a class of drugs called proteolysis-targeting chimeras, or PROTACs, and Pfizer had high hopes for the program after paying $1 billion upfront to partner with Arvinas in 2021. Researchers were testing vepdegestrant as a monotherapy in estrogen receptor-positive, HER2-negative metastatic breast cancer. Patients were in the second-line setting, having previously received CDK4/6 inhibitors and hormone therapy. Vepdegestrant isn’t completely dead, as Pfizer and Arvinas will still seek approval. Despite its apparent lack of effect in the overall trial population, the drug cut the risk of progression or death by at least 40% (the companies did not provide the exact figure) compared to the hormone therapy Faslodex in patients with mutated estrogen receptor genes. But it may not get as broad a label as investors and executives may have wanted. 🧬 Beam Therapeutics, meanwhile, saw some good news when it reported this week that an experimental base editing treatment helped lower levels of mutant proteins — and increase levels of corrected proteins — in nine people with a rare lung disease. The one-time therapy reduced levels of mutant proteins by 11% and 38% in the first two dose levels. And, in one patient at the highest dose, the treatment reduced levels of mutant protein by 78%. Beam is still deliberating whether it will test higher doses. The company claims it’s the first clinical results using base editing to directly correct a disease-causing mutation. It’s also Beam’s first trial results using in vivo base editing, which is considered to be a sort of CRISPR 2.0 with its ability to insert single-letter changes to the DNA. There were no side effects, and the protein was detected within three days of treatment. 🤝Roche and Zealand Pharma will collaborate on the biggest obesity partnership to date, with Roche ponying up $1.65 billion upfront for an amylin analog called petrelintide. Including milestone payments, the deal could be worth up to $5.3 billion. They plan to test petrelintide in combination with some of Roche’s other pipeline programs, including the GLP-1/GIP agonist CT-868, and a pill called CT-996. Zealand CEO Adam Steensberg told Endpoints News that obesity will be the first indication, “with an ambition of rapidly expanding.” Bristol Myers also got in on the action, acquiring its troubled cell therapy partner 2seventy bio, which spun out from bluebird bio, for $286 million in cash. The companies are partnered on the CAR-T therapy Abecma. 2seventy has fallen on hard times of late, having sold off most of its R&D work to Regeneron and laying off staff. BMS is buying 2seventy for $5 per share after the company peaked at $38 — but 2seventy fared better than bluebird, after SEC documents revealed its buyout offer shrunk from $100 million to $29 million. And in a smaller deal this week, Daiichi Sankyo and Johnson & Johnson both teamed up with Nosis Bio, a startup developing new ways to deliver RNA therapies to specific cells. Nosis was founded in 2021 and has only raised $13 million so far, but the two pharma deals could bring in more than $1.5 billion if all the milestones are met. Much remains unknown: Nosis did not disclose how much money it received upfront from Daiichi and J&J, nor did it say what kinds of cells or diseases the partnerships entail. A biotech advancing a once-monthly liver disease drug is exploring both an IPO and an acquisition. Boston Pharma is getting ready to launch a Phase 3 study in patients with metabolic dysfunction-associated steatohepatitis, a form of advanced fatty liver disease also known as NASH. For years, the condition was mainly treated with diet and exercise, until Madrigal Pharmaceuticals won the first approval last year. A handful of competitors are in late-stage trials, but Boston Pharma’s CEO Sophie Kornowski isn’t daunted. “I’m extremely motivated to do it well, and to do it fast,” she said. The agency said this week that it won’t allow employees who review new drug or medical device applications to take a $25,000 buyout offered to all HHS staffers. These include individuals in the CDER, CBER, CDRH, CVM, CTP and OC offices. The carveouts for staff funded by industry user fee dollars show the extent to which the FDA and HHS are not targeting drug and device reviewers in the Trump administration’s wider government staffing cuts.