In-vivo CAR-T inches toward clinical reality

A new Nature paper from Azalea Therapeutics, a spinout of Jennifer Doudna’s lab, offers an early but notable step toward in vivo CAR-T — engineering cancer-fighting T cells directly inside the body rather than through the laborious lab-driven process.

“It’s considered a holy grail in the field of gene therapy,” said Justin Eyquem, a co-founder of Azalea. “I’ve been doing this type of site-specific engineering, and we are always dreaming that one day we can do it in vivo.”

In mice, the team used a two-vector “double lock” system to precisely edit T cells and generate CAR-T cells capable of clearing both blood cancers and, notably, solid tumors, STAT’s Angus Chen writes. The process lessened the risk of off-target edits that have long plagued gene therapy. The approach could sidestep the logistical, financial, and clinical bottlenecks of current CAR-T. But the process would still likely have vector-related toxicities and adverse immune reactions.

The data are strong enough to justify human trials, but as with most things in gene therapy, the real question is whether the elegance of the biology survives contact with patients.

glp-1 drugs

Eli Lilly's 'triple-G' shows potency, raises concerns

Eli Lilly’s experimental “triple-G” drug retatrutide delivered striking results in a Phase 3 diabetes trial, driving blood sugar reductions on par with Mounjaro while producing unusually large weight loss, STAT’s Elaine Chen writes. Participants on the highest dose also lost 15.3% of their weight, while the placebo group lost 2.6%.

The results suggest the medicine could be highly beneficial for people who have diabetes and are also obese, a group estimated to make up around 60% of adults with type 2 diabetes, according to the Centers for Disease Control and Prevention.

RARE DISEASE

Charting the FDA’s course in the post-Prasad era

Will the FDA’s regulatory policies, particularly for rare disease drugs, shift in the wake of Vinay Prasad’s imminent departure from the agency?

STAT's Adam Feuerstein says he's paying close attention to the fate of six companies steering five drugs in front of the FDA over coming months. Collectively, how the agency handles these drugs should tell us more about the agency's current position on regulatory flexibility.

Among the companies: Replimune Group, Capricor Therapeutics, and Uniqure.

Check out the latest edition of "Adam's Biotech Scorecard" for more about those companies and the other three.

animal testing

FDA, NIH nudge drugmakers away from animal testing

HHS is accelerating a shift away from animal testing, with the FDA issuing draft guidance that effectively opens the door for drugmakers to use alternative methods, such as AI models and organ-like cell systems, without waiting for formal agency validation. And the NIH is taking action too, offering more than $150 million in funding for institutions studying ways to better simulate human biology, STAT’s Lizzy Lawrence writes.

“Technological advances are allowing us to move beyond animal testing in drug development, which has a poor track record of predicting safety and efficacy in humans,” FDA Commissioner Marty Makary said in a statement.

That said, some animal rights groups say the government’s efforts aren’t strong enough, while research advocates warn against sidelining animal studies too quickly.

rebranding

Drug pricing reform risks recreating 340B dynamics

The coming rollout of Medicare drug price negotiation for Part B drugs in 2028 could unintentionally recreate a system that resembles the 340B drug discount program, opines Sujith Ramachandran, an associate professor of pharmacy administration at the University of Mississippi. He says we need to “reform the root of the convoluted system” in place.

Lower negotiated prices will shrink the 6% add-on payments that outpatient clinics rely on, which ultimately could threaten billions in provider revenue — and trigger lobbying efforts on Capitol Hill.

“Reimbursement to health care providers for drug dispensing has been tied to the cost of the drug for far too long,” Ramachandran says in a new First Opinion. “Outpatient clinics should be compensated fairly for services they provide but not incentivized to dispense higher priced drugs just to get a larger profit from drug margin.

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