Lexeo's gene therapy for rare heart disease looks promising

Lexeo Therapeutics is developing a gene therapy meant to prevent deadly heart complications in patients with Friedreich's ataxia, a rare genetic disorder of the heart. The results are early and inconclusive but promising — and Lexeo is optimistic that it could win FDA approval, after another study.

"In my opinion, it sits squarely in the type of framework that Peter Marks has been sort of driving," Lexeo CEO Nolan Townsend told STAT's Jason Mast, speaking of the director of the agency's biologics division.

In an 11-patient study, the therapy showed some reduction in heart disease markers like left ventricle size and troponin levels. Although the data are encouraging, there's some concern that the patient pool is too small and the company has yet to show functional improvement in patients.

opinion

Do Medicare's new rules stifle drug innovation?

Medicare's new guidelines for drug price negotiations, part of the Inflation Reduction Act, might unintentionally stifle medical innovation, opines medical consultant and American Medical Association delegate Peter Rheinstein. CMS is interpreting the law in a way that lumps all medications with the same active ingredient into a single drug category, even if they are approved separately and used for different conditions. This could discourage pharmaceutical companies from investing in research to find new uses or improve existing drugs, he writes.

For example, the development of a once-daily pill version of tofacitinib for arthritis, which enhances patient adherence, might not have happened under these rules, Rheinstein argues. While the goal is to lower drug costs, CMS's approach could ultimately limit the development of new and potentially life-saving treatments. Instead, Rheinstein says that CMS should consider each drug separately if it received FDA approval on its own — to make sure that new drugs have the required time before facing price negotiations.

covid-19

What are the odds we get an heir to Paxlovid?

STAT's Matthew Herper weighs in from the Twitterverse: If your read Derek Lowe — and come on, you must read the bearded chemist who has been blogging about pharma for two decades — you've already thought about ibuzatrelvir, Pfizer's potential heir to Paxlovid, which would be given as a single pill and potentially without that metallic taste.

I read this eagerly, but I had another question that I asked virologist Michael Mina when he posted Derek's article on X. How do we test it?

Plenty of people still get Covid and die from it. But I've been watching clinical trials of Paxlovid and other antivirals. And these drugs keep failing in studies. Even Paxlovid worked best when it was given to high-risk people who have not been vaccinated. Shionogi's Paxlovid follow-up recently failed in a large study.

It's very hard to prove an antiviral drug works, a problem that has long dogged Tamiflu. The benefit only shows up if people are at very high risk, or if the study is very big. Otherwise, it just appears the drug is reducing symptoms a very tiny bit.

On this, David Boulware of the University of Minnesota had one perspective: Shionogi's drug failed because regulators wanted its study to contain too few high-risk patients. But my suspicion is that getting better Covid drugs will be less a problem of chemistry than of clinical trials. This is part of why we don't have more monoclonal antibodies against new strains. Paxlovid sales have come in higher than many analysts were expecting so far this year. Maybe that will encourage drug companies to solve this problem.

neuroscience

AI study shows brain variability based on sex, gender

Sex and gender uniquely shape brain connectivity, according to a new study using AI to analyze MRI scans of thousands of children. Researchers found that sex, largely influenced by biology, involved brain regions linked to vision and movement, while gender, defined by identity, had more diffuse brain network patterns. This highlights the need to consider both sex and gender separately in brain research.

Understanding how sex and gender influence brain connectivity in different ways could ultimately help improve how brain disorders are diagnosed and treated — allowing interventions to be tailored to individual needs.