The Food and Drug Administration on Thursday approved an Alnylam Pharmaceuticals medicine for a serious heart condition, a decision that should help the biotechnology firm secure its position as one of the sector’s most valuable companies.
The agency cleared the drug, called Amvuttra, for people with a cardiac form of the rare disease transthyretin amyloidosis. Alnylam already sells the therapy for individuals with a genetic type of the disease that causes progressive nerve damage.
Transthyretin amyloidosis with cardiomyopathy is considered deadlier than the nerve type, and often leads to hospitalizations and heart failure. It’s also thought to be more common, making it a target for drugmakers seeking a lucrative market opportunity.
In testing, treatment with Amvuttra led to a 28% lower risk of recurrent cardiovascular events or death from any cause than placebo in people with the disease. The drug similarly reduced that risk versus placebo among people who weren’t receiving another medication for the condition, Pfizer’s tafamidis, at the study’s start.
Both measures were the study’s main goals after statistical changes Alnylam made to the study a year ago.
Amvuttra labeling specifies treatment can reduce hospitalizations or death resulting from heart complications, as well as urgent visits for heart failure. That indication could help the drug’s commercial prospects, as tafamidis and the other available medication, BridgeBio Pharma’s Attruby, are also cleared for that use.
The approval provides a “new and clinically differentiated treatment option that has been shown to improve outcomes,” said CEO Yvonne Greenstreet, in a statement.
Alnylam didn’t disclose Amvuttra’s price in its press release. Tafamidis has a list price of over $250,000 while Attruby’s yearly cost is about $244,000.
Approval of Amvuttra in transthyretin amyloidosis, or ATTR, cardiomyopathy is important for the future of Alnylam, which pioneered a drugmaking method called RNA interference.
Though the company has developed four other marketed medicines — cementing itself as one of the industry’s most prolific developers — it’s still not profitable. Alnylam has accumulated a deficit of more than $7 billion since its 2002 founding, including $1.85 billion in combined net losses over the last three years, according to its most recent annual report.
Wall Street analysts and investors view approval in ATTR cardiomyopathy as Alnylam’s best opportunity yet to turn a regular profit. Historically, the disease has been underdiagnosed as it can be mistaken for other conditions. But better awareness, diagnostic tools and the availability of tafamidis since 2019 have grown the market, leading analysts to forecast annual sales for drugs that treat the condition rising to $15 billion to $20 billion over time. Global sales of tafamidis surpassed $5 billion last year.
Alnylam has sought to prove its medicines can deliver powerful benefits by “silencing” the misfolded protein implicated in the disease rather than stabilizing it like tafamidis does. The company came close to an approval with an earlier drug, Onpattro. But the FDA rejected it in 2023 after determining the supportive data weren’t meaningful enough to warrant an OK, and Alnylam abandoned seeking a clearance of Onpattro in cardiomyopathy.
The company tried again with Amvuttra, which works similarly to Onpattro but is administered through an under-the-skin injection rather than an infusion. Alnylam also ran the main trial supporting its approval for long enough to assess whether treatment could extend lives — the kind of evidence underlying tafamidis’ approval — and detected a benefit that appears to have satisfied U.S. regulators.
Amvuttra’s sales potential may not end up being as high as some on Wall Street predict, however. The drug will compete for market share tafamidis and Attruby, both of which are taken orally. The latter was approved last year and is off to a faster-than-expected start. Alnylam’s drug wasn’t tested directly against either one and, while cross-trial comparisons can be misleading, its results don’t appear strong enough to indicate vutrisiran is clearly superior. Physicians interviewed by BioPharma Dive last year said that deciding which drug to start new patients on, or switch to if one therapy stops working, will be difficult.
Given the drugs’ costs, insurers may not approve use of Amvuttra alongside tafamidis or Attruby. Generic versions of tafamidis, which could arrive later this decade, will further shift the market balance. Ionis Pharmaceuticals and Intellia Therapeutics are advancing other medicines, meanwhile.
In an interview ahead of the FDA’s decision, Chief Commercial Officer Tolga Tanguler said Amvuttra can help grow the market. While diagnosis rates have climbed since tafamidis’ initial approval, the majority of patients aren’t on treatment, leaving room for new entrants to gain share, he said.
Tanguler said Alnylam sees Amvuttra as “well positioned to become the standard of care.” He noted how adherence to the drug, which is injected four times a year, is very high in the neuropathy form of ATTR. “You don’t get that on an oral therapy,” he added. Good results “can only happen if you’re actually taking your medicine.”
Alnylam’s therapy also was tested in people who were already on other background therapies, among them tafamidis, which “set the bar very high.” Amvuttra nevertheless succeeded, with benefit reported across different subgroups.
“I have every confidence we’ll be able to communicate that very effectively to both payers and prescribers,” Tanguler said.
The company projects Amvuttra and Onpattro will generate about $1.6 billion to $1.7 billion in combined revenue this year, versus just over $1.2 billion last year. Tanguler expects Amvuttra’s usage to grow over the second half of the year and accelerate after.
