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Good morning. It’s the first real workweek of 2025 and we’re already starting to get a pickup in news again, so let’s get straight into it.
The need-to-know this morning
- Privately held Metsera reported placebo-adjusted weight loss of 6% in a cohort of 20 participants treated for 12 weeks with a titrated monthly dose of its experimental GLP-1 injection, called MET-097i.
- Privately held Orna Therapeutics and Vertex Pharmaceuticals signed a research collaboration to use Orna’s non-viral delivery technology in an effort to develop an in-the-body, genetic treatment for sickle cell disease.
Google’s anti-aging moonshot disappoints
Back in 2013, Google said it would attempt to understand and ultimately slow aging through a company called Calico. The first data have finally emerged from a drug Calico developed — it failed.
The pill, known as fosigotifator, was being tested in ALS. It wasn’t designed to slow aging itself. The FDA doesn’t consider aging a disease, so most so-called “longevity” companies have started by tackling specific age-related diseases.
In a large, multi-arm trial, fosigotifator failed to slow patients’ decline more than placebo over a 24-week period, although Calico did note that patients who received an “exploratory high dose” appeared to maintain muscle and respiratory function longer than placebo patients.
Read more from STAT’s Jason Mast.
FDA tries to start regulating AI in drug development
The FDA released a spate of new guidance documents yesterday ahead of the transition to a new administration. Among them was the agency’s first draft guidance on the use of AI in drug development.
The draft guidance doesn’t capture how AI is being used in drug discovery, but instead focuses on AI models used to produce data that support regulatory decision-making about the safety, effectiveness, or quality of drugs.
It suggests sponsors reach out to the FDA early about any potential uses of AI, and that they come prepared with proposed plans to establish the credibility of a model’s output — the higher the risk, the more stringent the criteria.
Read more from STAT’s Katie Palmer.
FDA wants confirmatory trial enrollment to start early
The agency yesterday also released draft guidance on the confirmatory trials that drugmakers must conduct if their treatments receive accelerated approval. Back in 2023, Congress had given the FDA the authority to require that a confirmatory trial is “underway” prior to granting accelerated approval. This new draft guidance defines how the FDA would define “underway.”
It says that soon after the end of Phase 2 trials, drugmakers should reach an agreement with the agency on the confirmatory trial design. It also says that enrollment in the trial should have already begun prior to accelerated approval.
Eva Temkin, partner at law firm Arnold & Porter, said that the agency had already been encouraging drug companies to start enrollment early on a case-by-case basis. “The real shift that that I think FDA is trying to emphasize in their guidance — that there is now going to be a presumption for all accelerated approvals, rather than this case-by-case” basis, she said.
Temkin also said it was noteworthy that the draft guidance discusses how making a drug available through an accelerated approval can make it difficult to recruit patients into a confirmatory trial. In these cases, drug companies should mitigate this effect, the FDA says, “by completing all or a significant portion of enrollment prior to accelerated approval.”
The draft guidance does leave some flexibility for drugs in very rare diseases. In situations where there are particularly small populations with high unmet need, and if appropriate justification is provided, the agency may not require a confirmatory trial be “underway” prior to accelerated approval, the document says.
J&J’s lung cancer drug extended survival
From my colleague Angus Chen: A year and a half ago, AstraZeneca showed Tagrisso could reduce the risk of death by 51% for patients with non-small cell lung cancer, an achievement that experts called “extraordinary.” Soon, patients may get yet another major advance in the treatment of EGFR-mutant non-small cell lung cancer. The topline results of the MARIPOSA trial showed that Johnson & Johnson’s Rybrevant combined with Lazcluze has a significant overall survival advantage over Tagrisso alone, according to company officials.
Patients with advanced cancer typically live a median of three years on Tagrisso, said Biljana Naumovic, president of U.S. oncology solid tumors at J&J. The combination of Rybrevant and Lazcluze should extend that by at least one year, she said. “This is really the first time in a decade that any combination of therapies has shown overall survival benefit versus standard of care.”
The median overall survival has not yet been met in the MARIPOSA trial, Naumovic said.
Can an epilepsy drug do more than reduce seizures?
From my colleague Adam Feuerstein: In a first-of-its-kind Phase 3 study, Stoke Therapeutics will assess the effect of its experimental treatment on seizures, but also evaluate potential improvements in cognition and behavior of patients with Dravet Syndrome, a severe form of epilepsy.
The company said today that it reached an agreement with the FDA, along with regulators in Europe and Japan, for it to green-light the Phase 3 study of zorevunersen in the middle of the year.
“To show improvement in cognition would set us apart from every other drug that is approved for Dravet. It’s never been done before,” Stoke CEO Ed Kaye told STAT in December, after the company presented promising new data from a mid-stage study.
The Phase 3 study, dubbed EMPEROR, will evaluate zorevunersen against a sham comparator in approximately 150 participants with Dravet aged 2-18. While reductions in seizure frequency — the study’s primary goal — can usually be measured after three to four months, Stoke will run the study for a full year so that it can fully assess secondary endpoints that will track changes in cognition and behavior.
“EMPEROR is unlike any study ever conducted for Dravet syndrome. It is going to be longer and more involved than studies of anti-seizure medicines, but the potential impacts of disease modification, as we have been discussing, are monumental,” said Kim Parkerson, Stoke’s head of neurology clinical development.
Eli Lilly allowed to intervene in compounding lawsuit
Yesterday, we wrote that Eli Lilly wanted to intervene in a lawsuit that a compounding trade group filed against the FDA, over the agency’s declaration that Eli Lilly’s tirzepatide (aka Mounjaro/Zepbound) is no longer in shortage.
A quick update on that front — the judge has granted Lilly’s request to join the lawsuit as a defendant.
The trade group, called the Outsourcing Facilities Association, has been arguing that the shortage isn’t actually over and compounding pharmacies should still be able to make copies of the branded treatments. Lilly, meanwhile, has wanted to join the lawsuit “protect its interests and help bring this suit to a swift end,” according to a legal filing last week.