FDA clears Denali's Hunter syndrome drug

The FDA yesterday granted accelerated approval to Avlayah, an enzyme replacement drug for Hunter syndrome developed by Denali Therapeutics. It's a notable moment after a series of harsher calls on rare disease drugs by the agency. The FDA recently rejected gene therapies from Regenxbio and Ultragenyx, raising questions about whether Denali's would meet a similar fate.

Avlayah, designed to cross the blood-brain barrier and potentially address cognitive decline, was reviewed by CDER, not CBER, and got through on biomarker-backed data, STAT's Andrew Joseph and Jason Mast write. The early approval offers relief to families who worried that innovation was slowing in this space.

"Generations of Hunter Syndrome and MPS families have fought for this exact moment," one patient advocate told STAT. "May the FDA never again underestimate the rare disease community."

rare disease

Sarepta's rebound hinges on early RNA signals

Sarepta Therapeutics yesterday offered a cautiously encouraging glimpse of its rebuild after last year's tumult, sharing early data on two RNA-based therapies for rare, muscle-wasting disease.

Shares jumped 20% after initial results showed strong gene-silencing in a handful of patients with facioscapulohumeral muscular dystrophy and more modest — and very preliminary — effects in myotonic dystrophy type 1, STAT's Damian Garde writes. Still, the dataset is tiny, and pivotal trials won't come until next year.

"We have a lot of work to do," CEO Doug Ingram, who will retire later this year, said on an analyst call.

Even unrelated serious adverse events will draw scrutiny given the company's recent history. After a brutal year marked by safety setbacks and a collapse in its Duchenne franchise, Sarepta is essentially asking investors to believe again — this time in RNA knockdown drugs licensed from Arrowhead Therapeutics. It's racing competitors like Vertex Pharmaceuticals, Dyne Therapeutics, and Novartis in an increasingly crowded field.

cell therapy

Allogene hopes to make strides toward off-the-shelf CAR-T

Allogene Therapeutics is pushing toward a make-or-break moment with its off-the-shelf CAR-T therapy cema-cel, STAT's Adam Feuerstein writes in his Biotech Scorecard newsletter. An upcoming interim readout from the ALPHA3 study could validate — or further undermine — a long-struggling strategy in B-cell lymphoma.

The company is testing whether giving cema-cel earlier, in patients who are in remission but still have a handful of cancer cells present — or "minimal residual disease." It wants to see if the cell therapy can delay or prevent relapse; if it does, the data could potentially position cema-cel as the first off-the-shelf CAR-T therapy approved in blood cancer.

"That's why this [Allogene] study is so interesting, because it is really the first that is trying to answer the question, if you have a complete remission with [minimal residual disease] positivity, does this approach [using an off-the-shelf CAR-T therapy] improve things for patients?" said David Qualls, a lymphoma expert at Dana Farber Cancer Center who was not involved in the study.

cancer

Corcept gets an approval in ovarian cancer

Corcept Therapeutics has salvaged its lead drug after an earlier FDA rejection, winning approval for relacorilant, which will be marketed as Lifyorli. The approval is for platinum-resistant ovarian cancer, where Corcept's drug can be used alongside the ubiquitous Abraxane.

The decision, which came earlier than expected, is backed by Phase 3 data showing a meaningful survival benefit, with a 35% reduction in risk of death and a roughly four-month median overall survival gain versus chemotherapy alone. The drug works by blocking cortisol signaling to make tumors more susceptible to chemo. Last year, Corcept tried to win FDA approval for relacorilant for a very different indication — Cushing's syndrome.

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