Alnylam shares dropped by a quarter on Thursday, with analysts suggesting the decline puts the RNAi specialist within range for a takeout.
Alnylam managed a 59% increase in revenue for its transthyretin franchise in the third quarter but a convergence of uncertainties has sent the big biotech “back to the penalty box,” according to analysts.
The franchise, which includes Amvuttra and Onpattro, collected $1.15 billion for the period, a major increase over the same period a year earlier. But the remaining quarter will be a tough slog for Alnylam, with pressures on inventory and pricing.
“While we remain positive on the TTR franchise and Alnylam’s long-term prospects overall, the trifecta of uncertainties is placing significant pressure on the stock,” BMO Capital Markets wrote on Friday morning.
Alnylam’s shares fell by a quarter at market close to $174. The stock is down 56% year to date. Alnylam currently has a market cap of $23.3 billion.
Oppenheimer said the plummeting stock has grown the case for a potential takeover of Alnylam, with Sanofi the most likely buyer.
On a Thursday earnings call, CEO Yvonne Greenstreet admitted that, despite a large effort to build out Amvuttra, the uptake has not been what the company had hoped.
“Look, we’re not satisfied with the pace of our future demand growth, and we need to do better,” Greenstreet said. “That being said, we have delivered substantial growth since the launch. It’s early days, and we think we’ve got significant opportunity ahead of us, and we’ve built a very strong foundation. And all the market fundamentals remain favorable.”
Greenstreet professed confidence in the clinical profile of Amvuttra in transthyretin amyloid cardiomyopathy (ATTR-CM), pointing to clinical evidence that the TTR silencer has shown a reduction in death and cardiovascular events.
Amvuttra was initially approved by the FDA in 2022 for ATTR with polyneuropathy (ATTR-PN). The drug was cleared for ATTR-CM in March 2025. The second launch has not been smooth, with Alnylam forced to cut guidance earlier this year as sales for the drug fell short of analyst expectations. Pressure is building on the franchise as competitors from BridgeBio Pharma and Pfizer steal market share.
Also putting pressure on Alnlyam is the upcoming 340B drug pricing rule update, which will impact the pool of money available for certain drugs—Amvuttra included—offered through Medicare.
“While the proposed rule would not become effective until January 1, 2027, our interactions with health systems over the last few months suggests that it could create Q4 ordering volatility as providers assess the implications for their economics and site of care choices,” CFO Jeffrey Poulton explained.
Alynlam has declined to say how much of its Amvuttra volume will be impacted by the 340B changes, but Truist Securities estimates that about 15-20% could be “directly exposed,” according to a Thursday note.
Greenstreet insists that the physicians who give Amvuttra a try prefer it with their patients. Alnylam has therefore been targeting the two-thirds of potential prescribers who have yet to write a script.
“What we need to do is build familiarity to drive adoption,” she said. “We’re very confident that we’ve made the right investments, and this is the right strategy, and we’re focused on driving execution with urgency.”
Meanwhile, Greenstreet warned analysts not to expect growth for the fourth quarter as that work continues.
Alnylam reiterated its guidance on Thursday, with expectations of net product revenue between $4.7-$5.1 billion, with the TTR franchise landing between $4.2-$4.5 billion. Poulton said revenue for the full year will likely fall on the low end of that scale.
Investors will have to wait for 2027 guidance, too. While Alnylam traditionally releases its next year expectations prior to the J.P. Morgan Healthcare Conference, which takes place mid-January every year, analysts noted that executives have pushed that out to February 2027.
“We view the departure from historical guidance timing as another indication of heightened uncertainty entering 2027,” Truist wrote.
