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Positive results in the HELIOS-B trial could support an expanded approval of Alnylam’s drug vutrisiran in transthyretin amyloidosis cardiomyopathy.
An experimental medicine helped people with a deadly heart disease stay out of the hospital and live longer in a closely watched clinical trial, a finding that could pave the way for a regulatory approval and help its developer, Alnylam Pharmaceuticals, rebound from a significant setback.
Trial data released Monday showed trial participants with the disease, transthyretin amyloidosis cardiomyopathy, and treated with Alnylam’s drug had a 28% lower risk of death from any cause or recurrent cardiovascular event, compared to those given a placebo. Alnylam said its drug was associated with a 33% risk reduction versus placebo among people who weren’t on another drug for the condition, Pfizer’s tafamidis, at the study’s start.
Both comparisons were parallel main study goals after statistical changes Alnylam made to the study in February.
Treatment with the medicine, called vutrisiran and sold as Amvuttra for a different form of the disease, was associated with significant improvements in secondary measures of heart health, Alnylam said.
Researchers also analyzed vutrisiran’s impact on survival alone and found treatment led to a 36% reduction in the risk of death in the overall study population up through 42 months. That figure was 35% for study volunteers not on tafamidis.
Alnylam said the benefits of treatment were consistent across major subgroups of trial participants, including those with different levels of disease severity. Rates of adverse events, serious adverse events and side effects leading to study discontinuation were similar between drug and placebo arms. Among volunteers receiving vutrisiran, no adverse events were at least 3% more common than placebo, the company said.
“There’s absolutely zero question about the robustness of this result,” said Alnylam’s Chief Medical Officer Pushkal Garg, on a Monday conference call with analysts. “This is not a chance finding. This drug has profound activity in this disease.”
Still, the company didn’t provide full trial details, leaving some questions about the drug and its benefits unanswered. Full study data will be disclosed at the European Society of Cardiology meeting at the end of August.
Alnylam plans to submit the results to regulators for approval and use a so-called priority review voucher to speed up its evaluation.
The data “support vutrisiran becoming a blockbuster in TTR-cardiomyopathy,” wrote Stifel analyst Paul Matteis, in a note to investors on Monday. Shares surged by as much as one-third in early trading Monday, reaching levels the company hasn’t hit since late 2022.
The results are a needed boost for Alnylam, one of the biotechnology sector’s largest companies and a pioneering developer of a drugmaking method called RNA interference. Though Alnylam has brought four rare disease drugs to market and discovered a cholesterol-lowering medicine now sold by Novartis, it hasn’t been consistently profitable. The company lost $440 million in 2023 and $1.1 billion the year prior.
Success in transthyretin amyloidosis cardiomyopathy could change that. While Alnylam already sells vutrisiran and a similar, earlier medicine called Onpattro for the rarer “polyneuropathy” form of the disease that affects the nerves, the type that causes heart damage is more prevalent. Alnylam has estimated that more than 250,000 worldwide have the cardiomyopathy form, compared to between 30,000 to 50,000 in the U.S. and Europe who have polyneuropathy. The only available drug for the condition, tafamidis, generated $3.3 billion last year, making it a top-selling medicine for Pfizer, which sells it as Vyndamax.
Alnylam has sought to top Vyndamax, first with Onpattro and now vutrisiran. It came close with Onpattro, reporting success in a Phase 3 study in 2022. But the Food and Drug Administration rejected its application last year, arguing the company’s study results weren’t meaningful enough to warrant approval.
Alnylam later abandoned plans to seek approval of Onpattro in cardiomyopathy. In the meantime, a pill similar to Pfizer’s and developed by BridgeBio Pharma succeeded in testing, adding another potential competitor to the mix. The FDA could approve that drug by November.
Vutrisiran works similarly to Onpattro, but is administered via a subcutaneous injection rather than by infusion. Unlike the shorter study of Onpattro, Alnylam ran vutrisiran’s trial long enough to tell whether the drug could extend lives and prevent hospital stays — the kind of benefits that supported the approval of Vyndamax.
Analysts’ expectations were high because of Onpattro’s performance in clinical testing and the potential that drugs like it may be superior to Pfizer’s and BridgeBio’s pills. Whereas those oral medicines are designed to “stabilize” the misfolded protein, transthyretin, that causes the disease, RNA interference therapies stop it from being made.
Though the “debate rages on,” experts interviewed by the investment bank Stifel “believe the silencer mechanism should be superior,” Matteis wrote earlier this year.
Debate will likely intensify further following Alnylam’s results. BridgeBio’s drug was associated with a 25% relative reduction in the risk of death in its Phase 3 trial, and a 50% relative risk reduction in hospitalizations.
Comparing drugs across trials can be misleading, though. And in transthyretin amyloidosis cardiomyopathy, there are “varying patient demographics,” making comparisons tougher, Matteis wrote. Still, vutrisiran “at the very least looks like it will be the go-to second-line” drug for the condition, “while also fighting for first-line use,” he wrote.
Matteis also noted what he described as a “highly robust benefit on top of tafamidis.”
BridgeBio shares fell by as much as 18% in early trading Monday.
The next big readout for TTR cardiomyopathy will come in 2025, when AstraZeneca and Ionis Pharmaceuticals are expected to reveal the results of a Phase 3 study testing another type of “silencer” called eplontersen.
Intellia Therapeutics and partner Regeneron also have a gene editing treatment for the disease that’s in late-stage testing.
Editor’s note: This story has been updated with executive commentary and stock price changes.
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Recent biotech company acquisitions have put emerging schizophrenia treatments in focus. But many development hurdles still stand in the way of new medicines for the brain.
The first medicine approved for PPD, Sage’s Zulresso, never gained traction. The company is in the midst of launching its second, but long-standing challenges could slow uptake.
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