Stoke, Johnson & Johnson, Google’s Calico

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Good day. It’s the first real work week of 2025 and we’re already starting to get news again, so let’s get right to it.

The need to know this morning

• Metsera, privately owned reported placebo-adjusted weight loss of 6% in a cohort of 20 participants treated for 12 weeks with a titrated monthly dose of their experimental GLP-1 injection, called MET-097i.
• Privately owned Orna Therapeutics and Vertex Pharmaceuticals signed a research collaboration use Orna’s non-viral delivery technology in an effort to develop an in-body genetic treatment for sickle cell anemia.

Google’s anti-aging project disappoints

In 2013, Google said it would try to understand and ultimately slow aging through a company called Calico. The first data finally emerged from a drug developed by Calico that failed.

The pill, known as fosigotifator, was being tested in ALS. It was not designed to slow aging itself. The FDA does not consider aging a disease, so most so-called “longevity” companies have started by addressing specific age-related diseases.

In a large multi-arm trial, fosigotifator failed to slow patients’ deterioration more than placebo over a 24-week period, although Calico did note that patients who received a “high exploratory dose” appeared to maintain muscle and respiratory function. for longer than the placebo. patients.

Read more by STAT’s Jason Mast.

The FDA is trying to start regulating AI in drug development

The FDA published a series of new guidance documents yesterday before 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 Among them was the agency’s first draft guidance on the use of AI in drug development.

The draft guidance does not capture how AI is used in drug discovery, but rather focuses on the AI ​​models used to produce data to support regulatory decision-making about the safety, efficacy or quality of medicines.

He suggests that sponsors contact the FDA in advance about any potential use of AI and come prepared with proposed plans for establishing the credibility of a model’s output: the higher the risk, the stricter the criteria.

Read more by STAT’s Katie Palmer.

FDA wants confirmatory trial enrollment to start early

The agency also published draft guidance yesterday on the confirmatory trials that drugmakers must conduct if their treatments receive accelerated approval. In 2023, Congress had given the FDA the authority to require a confirmatory trial to be “in place” before granting accelerated approval. This new draft guidance defines how the FDA would define “ongoing.”

It says that soon after the end of Phase 2 trials, drugmakers should reach an agreement with the agency on the design of the confirmatory trial. It also says enrollment in the trial should have already begun before accelerated approval.

Eva Temkin, a partner at the law firm Arnold & Porter, said the agency had already been encouraging drug companies to start enrollment early, on a case-by-case basis. “I think the real change that the FDA is trying to emphasize in its guidance is that there will now be a presumption for all expedited approvals, rather than a case-by-case basis,” he said.

Temkin also said it was noteworthy that the draft guidance discusses how making a drug available through accelerated approval can make it more difficult to recruit patients for a confirmatory trial. In these cases, drug companies should mitigate this effect, the FDA says, “by completing all or a significant portion of the enrollment prior to accelerated approval.”

The draft guidance leaves some flexibility for drugs in very rare diseases. In situations where there are particularly small populations with large unmet needs, and if adequate justification is provided, the agency may not require that a confirmatory trial be “under way” before 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 that Tagrisso could reduce the risk of death by 51% in patients with non-small cell lung cancer, an achievement that experts called “extraordinary.” Soon, patients will be able to gain another important breakthrough in the treatment of EGFR-mutated non-small cell lung cancer. Topline results from 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 an average 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 period by at least a year, he said. “This is really the first time in a decade that any combination of therapies has shown an overall survival benefit compared to standard care.”

Median overall survival has not yet been reached in the MARIPOSA trial, Naumovic said.

Read more.

Can an epilepsy medication do more than reduce seizures?

From my colleague Adam Feuerstein: In a phase 3 study, the first of its kind, Stoke Therapeutics will evaluate the effect of its experimental treatment on seizures, but will also evaluate possible improvements in cognition and behavior in patients with Dravet syndrome, a severe form of epilepsy .

The company said today that it has reached an agreement with the FDA, along with regulators in Europe and Japan, to greenlight the Phase 3 study of zorevunersen by mid-year.

“Showing improvement in cognition would differentiate us from any other drug approved for Dravet. It’s never been done before,” Stoke CEO Ed Kaye told STAT in December, after the the company presented promising new data from a mid-stage study.

The Phase 3 study, called EMPEROR, will evaluate zorevunersen against a sham comparator in approximately 150 Dravet participants ages 2 to 18 years. While reductions in seizure frequency (the primary endpoint of the study) can typically be measured after three to four months, Stoke will run the study for a full year so that it can fully evaluate the secondary endpoints that will track the changes. in cognition and behavior.

“EMPEROR is unlike any study ever done on Dravet syndrome. It’s going to be longer and more complicated than anti-seizure drug studies, but the potential impacts of disease modification, as we’ve been discussing, are monumental,” said Kim Parkerson, head of neurology clinical development at Stoke.

Eli Lilly Allowed to Intervene in Composite 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 statement that Eli Lilly’s tirzepatide (also known as Mounjaro/Zepbound) is no longer in short supply.

A quick update on that front: the judge 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 really over and that compounding pharmacies should still be able to make copies of brand-name treatments. Meanwhile, Lilly has wanted to join the lawsuit “to protect its interests and help bring this lawsuit to a quick end,” according to a legal document filed last week.

More readings

• Four years after AlphaFold’s AI ‘solved’ protein structure, fierce competition continues. STATISTICS
• Wearable device maker ActiGraph acquires assets from Biofourmis to boost clinical trial offerings. STATISTICS
• Health care is UPS’s $20 billion lifeline to offset shipping slowdown. Bloomberg