Alnylam Pharmaceuticals’ stock price plummeted as much as 29% Thursday morning after disappointing Amvuttra sales and a lowered full-year forecast triggered renewed fears over the transthyretin amyloidosis (ATTR) franchise.
It was the first quarter Amvuttra sales crossed the $1 billion mark, but its $1.01 billion haul missed analysts’ expectations by 4%. In the U.S., the RNA interference therapy brought in $809 million, or 2% below consensus.
As Amvuttra had repeatedly topped Wall Street’s projections since its key FDA approval in ATTR-cardiomyopathy in March 2025, the weakness in the second quarter of 2026 came as a surprise, triggering the selloff. As Jefferies analysts pointed out in a Thursday note, investors were expecting a low-single-digit percentage beat ahead of the announcement.
The underwhelming performance led Alnylam to lower its full-year guidance, with the company now expecting total ATTR revenue to land in a range between $4.2 billion and $4.5 billion, representing a $200 million cut at both ends.
During an investor call Thursday, Alnylam CEO Yvonne Greenstreet, M.D., attributed the cut to normalized second-line growth after the drug benefited significantly from pent-up demand for a new therapy last year.
Nevertheless, pointing to patient demand in the first-line setting, Greenstreet said, “our confidence in Amvuttra’s growth trajectory has never been stronger.” Roughly 80% of new ATTR-CM treatment starts in the overall market are for first-line treatment, and that’s where Alnylam is focused, she noted.
Chief Commercial Officer Tolga Tanguler spent quite some time on Thursday’s call assuring investors that Amvuttra’s launch is progressing well and its long-term potential remains intact.
“Access remained broad, pull-through was strong, and adherence continued to exceed 90%,” Tangular said of Amvuttra in the U.S., where Alnylam’s total ATTR revenues recorded 15% growth sequentially versus the first quarter of 2026. The pace of U.S. underlying demand growth for Amvuttra more than doubled in the second quarter compared to the previous three months, he added.
Among physicians who already prescribe Amvuttra, the drug represents more than 50% of new patient starts, “underscoring the strong physician preference that develops with experience,” Tanguler said.
To further improve market penetration and expansion, Alnylam is accelerating its investments in diagnosis to identify patients earlier and to expand the treatable population, as well as in customer-facing activities to add more physicians to its prescribing base, according to the commercialization chief.
Two major developments in the ATTR-CM field “have cleared the path for us to be even more competitive in the first-line setting,” which has been Alnylam’s priority, Tangular said.
Pfizer recently announced that it fought back a generic challenge to its Vyndamax (tafamidis) to 2031. Then, in a high-profile setback, AstraZeneca and Ionis’ silencer Wainua failed in ATTR-CM in the CARDIO-TTRansform trial, likely eliminating a key competitor for Amvuttra.