Dive Brief:

• Alnylam Pharmaceuticals lost nearly 30% — or close to $12 billion — of its market value after the company surprised investors by lowering financial forecasts for its most important drug franchise by $200 million.
• The RNA-focused biotechnology company had previously predicted those drugs, the transthyretin amyloidosis medications Amvuttra and Onpattro, would bring in $4.4 billion to $4.7 billion. But in an earnings report Thursday, it dropped that estimate to between $4.2 billion and $4.5 billion, revealing that Amvuttra’s early launch spike benefitted from “pent-up demand” that’s since “normalized.”
• Alnylam has been in a high-stakes battle over the last year to carve out a share of the multibillion-dollar “TTR cardiomyopathy” market, which has become increasingly competitive thanks to drugs like Pfizer’s Vyndamax, BridgeBio’s Attruby and, potentially, AstraZeneca and Ionis Pharmaceuticals’ eplontersen.

Dive Insight:

Alnylam had already seen its share price slide by a double-digit percentage after a study setback for eplontersen in July raised thorny questions about how useful drugs like Amvuttra are in patients on other treatment.

The latest news, then, represented a “one-two punch” for Alnylam that may hang over the company until the presentation of that failed study at a medical meeting in late August, wrote Cantor Fitzgerald analyst Olivia Brayer Saunders.

“We knew expectations for 2026 were ambitious, but we weren’t expecting a guidance cut,” she wrote.

Oppenheimer analyst Kostas Biliouris echoed that sentiment in his own note. While some investors may have been expecting a guidance reduction, “it comes as a surprise to us” for one to come this early in the year, especially since prescription rates tracked by healthcare data specialist Iqvia suggest the company could meet its original predictions.

Amvuttra sales totaled $1.01 billion for the quarter, or 3% below the average analyst estimate of $1.05 billion, according to Biliouris.

Alnylam shares traded around $200 apiece by late Thursday afternoon, down from a $286 close the previous day.

The earnings miss and guidance cut invites “major” questions on the outlook of Alnylam’s TTR business, wrote Jefferies analyst Faisal Khurshid. The “bull/bear debate ... is real, and today’s update underscores the complexity.”

Khurshid added that his team doesn’t envision “the overhang passing easily,” and is “not convinced there’s enough investor interest” in Alnylam’s pipeline to “make up for TTR uncertainty.”