A rare genetic mutation may delay early Alzheimer's

A new study bolsters evidence that a rare genetic mutation in apolipoprotein E3 (APOE3) may help delay early Alzheimer's, supporting efforts to develop therapies mimicking the mutation.

Researchers have long studied members of an extended family who carry a genetic variant that guarantees they'll get Alzheimer's. Scientists previously found that one woman in this family with two copies of the APOE3 mutation developed Alzheimer's 30 years later than expected. This new study now finds that people with just one copy of the APOE3 mutation also developed the disease several years later than people without any copies of the mutation.

The researchers found that while the people with the APOE3 mutation had plenty of amyloid, a protein that forms plaques in the brain associated with disease, those people had surprisingly little tau, a different protein that accumulates inside neurons and is linked to Alzheimer's disease severity.

gene therapy

Awaiting FDA's decision on Sarepta's Duchenne treatment

From STAT's Jason Mast: Sometime today or tomorrow, the FDA is expected to hand down a decision on whether it will broaden its approval of Elevidys, Sarepta's gene therapy for Duchenne muscular dystrophy.

The treatment has already lost much of the luster it held a few years ago, when there was hope it might cure or halt the disease, before it failed two consecutive randomized, placebo-controlled clinical trials. Still, many doctors and families see it as the best thing they've ever been able to offer their patients and the best thing on the horizon for at least a couple years.

The agency seems likely — based in part on comments from top official Peter Marks — to at least partially expand the approval for Elevidys, which is currently authorized only for 4- and 5-year olds. But it's unclear how broadly it will authorize access. Sarepta and much of the Duchenne community are hoping the agency will approve the treatment for nearly all patients with muscular dystrophy, regardless of age or wheelchair status.

Yet Sarepta has conducted only limited studies in older patients, in whom the treatment could be riskier and less beneficial, and hasn't released any data. Another option is an approval for only boys who can still walk or boys aged 4 to 7, the population studied in clinical trials.

pharma

Lilly takes more actions against unapproved versions of Mounjaro

After taking legal actions last year, Eli Lilly this morning filed even more lawsuits against med spas and wellness centers over unapproved versions of tirzepatide, the active ingredient in Mounjaro and Zepbound. Lilly said these entities misleadingly use the brand names, posing dangers for patient safety.

The pharma company also issued an open letter warning the public about the risks of these products.

With the immense demand for GLP-1-based drugs and recurring shortages of the branded treatments, a wide variety of businesses — from telehealth companies to med spas and compounding pharmacies — have popped up to offer their own versions of what they claim are GLP-1 drugs.

How much risk do compounded products actually pose? It's a complicated question. Compounding pharmacies are technically allowed to make copycat versions of approved medicines if those treatment are in shortage. Lilly argues in its open letter, though, that compounded products ultimately are not FDA-approved and lack the same quality protections as FDA-approved drugs. To learn more about this issue, my colleague Ed Silverman wrote a primer on this last year.

Aside from compounding pharmacies, patients have also turned to "research" websites that claim to sell the underlying chemicals in GLP-1 drugs. Patients have ordered from these websites, and then mixed and injected the chemicals themselves at home. Lilly also called out the risks of these websites in its open letter.

obesity

Task force recommends behavioral therapy over obesity drugs for children

In new recommendations issued this week, the U.S. Preventive Services Task Force favored intensive behavioral therapy over obesity drugs like Wegovy for children and teens with a high body mass index.

The task force said the evidence of benefits of obesity medications is "inadequate" due to the small number of studies and limited data on long-term treatment harm. This differs from recommendations from the American Academy of Pediatrics, which said obesity drugs should be considered for kids 12 and older whose weight tops growth charts.

There's been heated debate on whether children and teenagers should be widely prescribed obesity drugs. Some doctors have raised concerns about the lack of data not only on the physical long-term effects of the drugs, but also on how the treatments may affect mental health.

cardiovascular disease

An enormous stock-moving event for Alnylam Pharmaceuticals

STAT's Adam Feuerstein jumps in with a brief look at his Biotech Scorecard newsletter this week:

This week's Biotech Scorecard is devoted entirely to a preview of Alnylam Pharma's HELIOS-B study. For those unfamiliar, HELIOS-B is a Phase 3 cardiovascular outcomes study designed to answer one main question: Can Alnylam's RNA-interference therapy called vutrisiran improve the lives of patients with the progressive heart disease ATTR-CM?

The study outcome — expected at the end of June or early July — is an enormous stock-moving event for Alnylam. Billions of dollars in potential revenue are on the line. The results will also impact competitors, including BridgeBio Pharma and Ionis Pharmaceuticals.

HELIOS-B is one of the biggest binary events in biotech this year. The results are also likely to be a bit complicated. Hopefully, this week's newsletter will serve as your guide. Inside, you'll find background information, a look at how investors are defining success or failure, and some comments from Alnylam CEO Yvonne Greenstreet.

Lastly, an investor perspective from Daniel Schneeberger, founder and chief investment officer at Adar1 Capital Management, a biotech hedge fund. If you're a Twitter/X biotech person, you know Dan as the widely followed "Sheep of Wall Street."

Adam's Biotech Scorecard is delivered to STAT subscribers every Thursday morning. You can sign up for your own email copy here, or read it on the web here.

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