Despite the added survival benefit for its drug, Alnylam still faces steep competition from Pfizer, whose ATTR-CM therapies have become established treatment options.
Alnylam Pharmaceuticals on Friday revealed detailed data from the Phase III HELIOS-B study, which suggested that its RNA interference therapy vutrisiran can provide additional survival benefit for transthyretin amyloidosis cardiomyopathy patients who are already being treated with its blockbuster competitor, Pfizer’s Vyndamax (tafamidis).
A subgroup analysis of HELIOS-B at 42 months showed that in patients who were taking Vyndamax, add-on treatment with vutrisiran further reduced the risk of all-cause mortality by 41% versus placebo. The primary composite endpoint—composed of all-cause mortality and recurrent cardiovascular events—dropped by 22% in this subgroup.
Both effects, however, fell short of statistical significance, with p-values of 0.0983 and 0.2701, respectively, according to Alnylam’s news release.
Despite its potential additive effects, Friday’s results could pose competitive problems for Alnylam. Pfizer’s Vyndamax and sister brand Vyndaqel (tafamidis meglumine)—approved in May 2019—have firmly established a foothold in the transthyretin amyloidosis cardiomyopathy (ATTR-CM) space. The drugs earned $1.14 billion in the first quarter of 2024, hitting blockbuster status.
Alnylam’s shares dropped around 16% in premarket trading on Friday in response to the readout, according to Seeking Alpha.
Vutrisiran—approved in June 2022 as Amvuttra for polyneuropathy associated with ATTR—is a double-stranded siRNA therapeutic that works by targeting the mRNA of both mutant and wildtype transthyretin, tagging the molecules for destruction, according to its label. Through this mechanism of action, vutrisiran prevents the toxic build-up of the transthyretin protein, thereby addressing the underlying pathological pathway in ATTR.
In June 2024, the Cambridge, Massachusetts–based biotech unveiled topline data from HELIOS-B, touting a 28% reduction in the risk of the primary composite endpoint in the overall study population. Focusing on patients who were not taking any background therapies, vutrisiran lowered the likelihood of the primary outcome by 33%.
In the respective patient populations, vutrisiran cut the risk of all-cause mortality by 36% and 35% at 42 months.
Alnylam highlighted these data again in its news release on Friday, with Chief Medical Officer Pushkal Garg saying in a statement that the results “suggest that vutrisiran has the potential to become a new standard of care treatment for ATTR-CM, a progressive and ultimately fatal disease with limited treatment options.”
“In light of these data, we are working with urgency to file these data with regulators and bring this medicine to patients around the world,” Garg added.
Alnylam presented its detailed HELIOS-B findings on Friday at a Hot Line session at the 2024 Congress of the European Society of Cardiology. These data were simultaneously published in The New England Journal of Medicine.
