Third patient death tied to Sarepta gene therapy

From my colleague Jason Mast: A 51-year-old man died last month after receiving an experimental gene therapy developed by Sarepta Therapeutics for an ultra-rare form of muscular dystrophy, a company spokesperson confirmed late yesterday.

He is the third patient to die after getting a Sarepta gene therapy this year. All cases were tied to liver issues.

Two teenage boys died after receiving Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy, forcing the company to take the drug off the market for older patients. The 51-year-old man was in a clinical trial for limb girdle muscular dystrophy, a collection of rarer and generally slower-moving conditions.

The death will likely further stoke safety concerns around Sarepta’s gene therapies, as well as raise questions around the company’s transparency.

artificial intelligence

AI breakthrough may pave way to drugs for disordered proteins

Researchers in David Baker’s lab at the University of Washington have unveiled two AI-powered methods to design protein binders for intrinsically disordered proteins — shapeshifting molecules long considered undruggable. Published in Science and in a preprint, the studies from the Nobel laureate’s team describe tools to either cradle disordered targets into shape or assemble modular “pockets” that latch onto exposed amino acid pairs.

The breakthrough could open doors to targeting proteins implicated in diseases like Alzheimer’s, diabetes, and cancer, sidestepping decades of frustration in structural biology.

cancer

FDA advisory panel rejects Blenrep over eye risks

In a surprise setback for GSK, advisers to the FDA concluded yesterday that the risks of the company’s multiple myeloma drug Blenrep outweigh its benefits. The panel cited high rates of eye toxicity and lingering concerns over the selected dose, STAT’s Andrew Joseph writes.

Much of the discussion centered on blurred vision and corneal damage, with questions over whether U.S. patients being treated could realistically access the necessary eye care. FDA regulators had criticized GSK for not more thoroughly exploring lower, potentially safer doses during development — and for enrolling few U.S. patients in its pivotal studies.

“If a drug is so good, patients should be enrolled in the United States,” said Richard Pazdur, the agency's top oncology drug regulator.

BIOTECH

Ginkgo makes a push to take business from China

Ginkgo Bioworks, a former synthetic biology darling, is now leaning hard into contract research services — launching U.S.-based ADME (absorption, distribution, metabolism, and excretion) profiling designed to undercut or match pricing from Chinese and international vendors.

The new service promises to support small molecule drug discovery and machine learning applications. The move also signals a deepening pivot by Gingko from synthetic biology to CRO services, as the company continues to find its footing.

podcast

Inside an FDA rejection, and layoffs at Sarepta

Just how many employees is Sarepta Therapeutics laying off? And why did the Food and Drug Administration reject Ultragenyx's rare disease drug over manufacturing qualms? We discuss all that and more on this week’s episode of “The Readout LOUD.”

Ultragenyx CEO Emil Kakkis joins us to discuss what was in the rejection letter his company received late last week, and whether he still has confidence in FDA Commissioner Marty Makary. We also discuss Capricor's drug rejection, and Sarepta's decision to lay off hundreds of staffers, but give raises to some executives.

Listen here.

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