November 18, 2024

The need-to-know this morning

Syndax Pharmaceuticals won FDA approval for Revuforj, a new treatment for a genetically defined type of advanced leukemia.
Cybin said its drug based on psilocin, a psychedelic found in certain types of mushrooms, alleviated depressive symptoms in a mid-stage clinical trial.
Neurogene discontinued further development of a high dose of its gene therapy for Rett syndrome after a patient reported a potentially life-threatening side effect.

glp-1 drugs

New Zepbound data gives insights on hospitalizations but not much on deaths

From STAT's Elaine Chen: Over the weekend at the American Heart Association meeting in Chicago, researchers presented full results of a trial testing Eli Lilly's obesity drug Zepbound in patients with heart failure with reduced ejection fraction, or HFpEF. Lilly had previously announced topline results that Zepbound reduced the risk of major problems (heart failure-related urgent visits or hospitalizations, intensification of diuretic treatment, or cardiovascular deaths) — by 38% compared to placebo.

The full results, which were also published in NEJM, broke down the findings for each individual outcome. Notably, Zepbound led to a 56% reduction in heart failure-related hospitalizations.

But in the trial, which tracked about 700 HFpEF patients over two years, Zepbound did not reduce the risk of cardiovascular-related or all-cause death. There were eight cardiovascular deaths in the Zepbound group versus five in the placebo group, and there were 19 deaths from any cause in the Zepbound group versus 15 in the placebo group. These differences were not statistically significant, meaning they could have occurred by chance.

Additionally, among serious adverse events tracked, there were seven cases of atrial fibrillation in the Zepbound group versus three in the placebo group, and six cases of heart attack in the Zepbound group versus two in the placebo group.

What can be interpreted from these numbers on deaths and adverse events? Really not much. Experts told me the number of cases were too small and the trial was too short to interpret anything meaningful, and that we have to wait for the results of ongoing large outcomes trials to get a better understanding of Zepbound's effect on death and problems like heart attacks.

"These very small numbers are just that. I think it's just a play of chance," said A. Michael Lincoff, a cardiologist at Cleveland Clinic who wasn't involved in the trial.

Observers were anticipating these full results since it's the first time we're seeing data on how Zepbound affects outcomes like hospitalizations and deaths. Novo is ahead, as it's already gathered cardiovascular outcomes data on its obesity drug Wegovy. Novo has also pooled together data across different trials to show that Wegovy reduced the risk of hospitalizations and urgent care visits among HFpEF patients.

Gene Therapy

Regenxbio improves muscle function in boys with Duchenne muscular dystrophy

Regenxbio reported Monday the first clinical evidence showing improved muscle function in boys with Duchenne muscular dystrophy following treatment with its experimental gene therapy.

The positive results from muscle-performance tests come from a small number of patients, but after consulting with the Food and Drug Administration, Regenxbio has expanded its current clinical trial so that it can support the submission of an accelerated approval application in 2026.

If successful, the Regenxbio gene therapy, called RGX-202, could become the second genetic medicine for Duchenne to reach the market, following the accelerated approval of Sarepta Therapeutics' Elevidys in June 2023. It might also become the first Duchenne gene therapy accessible to children starting on their first birthday. Elevidys can't be given to children under 4.

crispr

Intellia's CRISPR drug promising in ATTR cardiomyopathy

A CRISPR-based drug made by Intellia Therapeutics showed promise in reversing ATTR cardiomyopathy. New year-long data from a Phase 2 study showed a 90% reduction in TTR protein levels in patients with the progressive heart disease, STAT's Jason Mast writes. They also performed better on a six-minute walk test than those taking existing treatments. That said, the jury's still out on how investors will view the data — and experts are still a bit cautious and waiting for confirmatory Phase 3 data comparing it to established therapies from Alnylam, Pfizer, and BridgeBio.

"I cannot predict the stock market. I find it highly irrational lately," Intellia CEO John Leonard told STAT. "We've shown that we have achieved what appears to be a functional cure, in what has been an incurable disease. And I think the [investor] notes that I've read have been largely uninformed or wide of the mark in terms of understanding what's meaningful to patients and doctors."

cancer

Increased cancer diagnoses among young people

Cancer's on the rise among people younger than 50, with a recent study pointing to an increase in 17 of 34 cancer types. Researchers are now exploring whether this is due to factors like obesity, diet, smoking, and expanded health screening. Speaking at the Milken Institute's Future of Health Summit this week, experts emphasized the need for more efficient, targeted tests and AI-driven tools to predict disease risks earlier. They also said that it's important to educate younger populations about the fact that they might get cancer sooner than they'd expect — but that treatments are also improving.

"We need to break the stigma of cancer, because right now, what was science fiction is becoming science reality in a clinic next door," Mohit Manrao, head of U.S. oncology at AstraZeneca, said during the panel discussion.

Drug development

Novartis makes moves in radiopharma

From STAT's Allison DeAngelis: Novartis is making further moves in its bid to maintain its lead in the radiopharmaceuticals field, striking a license and collaboration deal with startup Ratio Therapeutics.

Novartis sells the two leading targeted radiation treatments for cancers on the market, Lutathera and Pluvicto. But the field has boomed over the last two years, and competition is edging in. Several pharma companies have made acquisitions in the field, including Bristol Myers Squibb and Eli Lilly.

The Novartis-Ratio deal is focused on developing a treatment that targets a biomarker called SSTR2. Novartis' existing drug Lutathera hits that same target, but uses what's often considered a first-generation isotope. Meanwhile, rival Bristol Myers Squibb and its new acquisition RayzeBio are in the late stages of testing a SSTR2-targeting drug that uses what is generally considered a next-generation approach: an alpha isotope called actinium 225 that emits a more concentrated burst of radiation to decimate cancer cells.

Novartis and Ratio have not decided whether they, too, will focus on an alpha isotope. Ratio's pipeline is isotope agnostic. Under this agreement, Ratio will get as much as $745 million in a mixture of upfront and future payments based on development goals to develop a new drug candidate.

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