Vutrisiran Sodium

Alnylam Pharmaceuticals’ RNAi therapeutic vutrisiran has been recommended by the European Medicines Agency’s human medicines committee to treat adults with transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a potentially fatal disease of the heart muscle that occurs when misfolded transthyretin (TTR) protein accumulates and causes irreversible cardiovascular damage over time. The Committee for Medicinal Products for Human Use (CHMP) has recommended that the drug be authorised to treat both wild type and hereditary ATTR-CM. Administered as a subcutaneous injection once every three months, vutrisiran is designed to work with the body’s natural system to knock down TTR at its source. The drug is already approved in the EU under the brand name Amvuttra to treat hereditary TTR-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, and “has the potential” to be the first and only RNAi therapeutic to receive European Commission (EC) approval for ATTR-CM, according to Alnylam. The CHMP’s decision in ATTR-CM was supported by results from the phase 3 HELIOS-B trial, which met all ten of its pre-specified primary and secondary endpoints across both the overall and monotherapy populations. In the overall study population, which included patients receiving Amvuttra as a monotherapy and those using the therapy alongside standard treatments, Alnylam’s drug reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular events by 28% during the double-blind treatment period of up to 36 months. In the monotherapy population, Amvuttra reduced the risk of ACM and recurrent cardiovascular events by 33% in the double-blind period and the risk of mortality by 35% at month 42. Mortality in the overall population was also reduced by 36% at month 42. Alnylam’s chief medical officer, Pushkal Garg, said: “In the HELIOS-B study, vutrisiran treatment resulted in rapid knockdown of TTR and led to improved survival, fewer hospitalisations and less disease progression in patients with ATTR-CM, nearly half of whom were on a TTR stabiliser. “Combined with its quarterly dosing and well-established safety profile, we believe vutrisiran could offer an important new treatment option for patients in the EU.” The EC will now review the CHMP’s recommendation as it makes a final decision on vutrisiran in this indication.

Is the PDUFA delay for Stealth BioTherapeutics a canary-in-the-coalmine moment? Or is it an overblown one-off that signals little about disruption at the FDA? That’s the question seemingly on everyone’s minds after the FDA on Tuesday delayed a PDUFA date for Stealth’s new drug application. There weren’t safety or manufacturing concerns, the agency didn’t ask Stealth to conduct additional trials, and Stealth doesn’t know when a decision might get made. FDA Commissioner Marty Makary has pointed out that decision dates aren’t hard deadlines , but rather “target dates” the agency attempts to meet. That’s technically true: The law mandates that agency reviews meet a minimum of only 90% of the PDUFA dates it sets. “It’s not like missing a statutory deadline,” Patricia Zettler, an Ohio State professor who specializes in FDA law, told me this week. But the delay of Stealth’s PDUFA (as well as a delay for a post-CRL hearing from Vanda Pharmaceuticals) has people asking whether other stages of the regulatory process could be impacted. There are copious amounts of FDA work not tied to deadlines, like biomarker qualification programs , that could be slowed even if the FDA keeps largely hitting PDUFA dates. So far, most biopharma companies have said — both on earnings calls and in interviews with Endpoints — they aren’t seeing any impact on FDA reviews. And many recent PDUFA dates have been met without issues, including for Dupixent , Amvuttra , Sanofi’s RNAi drug for hemophilia and rare disease products from Amgen and J&J . Those applications coming through on time provide a significant counterpoint to the Stealth delay, Leerink analyst Daina Graybosch said. While Graybosch believes the agency will be affected by the layoffs (“it’s inevitable,” she said), it’s almost certainly too early to know how the changes at the FDA are going to affect US drug development and regulation. (Makary has argued that the regulator was overstaffed and inefficient before the cuts.) Graybosch didn’t follow the Stealth case closely, but she noted its exceedingly long development history and its drug having been previously rejected and delayed . “Blaming this on DOGE, I’m sorry, there’s so many things going on and ways and reasons to see risk,” Graybosch said. “Taking what happened at [Stealth] and reading into it more broadly feels alarmist to me.” But other analysts and FDA experts I spoke to agreed that the Trump administration’s healthcare staffing cuts are going against its stated goal of making government more efficient, and that firing hundreds of staff and slashing review teams will likely make the agency less effective at its job. “It may be too early to say things are chugging along just fine,” Zettler said. “Bigger questions are, ‘What about products that are earlier in development or are not as far along in their review process?’” —Max