Tafamidis

Transthyretin amyloid cardiomyopathy (ATTR-CM) has evolved from an untreatable condition to one managed with three FDA-approved disease-modifying agents: tafamidis, acoramidis, and vutrisiran.

• Alnylam Pharmaceuticals has received FDA approval for Amvuttra (vutrisiran) to treat ATTR cardiomyopathy (ATTR-CM), significantly expanding the drug's addressable patient population beyond its original polyneuropathy indication. • The approval represents a major advancement in treatment options for ATTR-CM patients, a progressive and often fatal condition characterized by the buildup of abnormal amyloid protein in the heart muscle. • This expanded indication strengthens Alnylam's position in the ATTR treatment market, potentially increasing the company's revenue stream while providing patients with a new therapeutic option for managing cardiac manifestations of the disease.

• An FDA advisory committee voted 9-3 in favor of approving Alnylam's Onpattro (patisiran) for transthyretin amyloidosis cardiomyopathy (ATTR-CM), with a final decision expected by October 8th. • Despite FDA reviewers questioning the clinical significance of Onpattro's modest efficacy in the APOLLO-B trial, the panel was swayed by the drug's established safety profile and potential to address the underlying disease mechanism. • If approved, Onpattro would compete with Pfizer's Vyndamax/Vyndaqel (tafamidis), which generated $2.5 billion in sales last year, marking another milestone for RNA interference technology following its historic 2018 approval for ATTR polyneuropathy.

• Alnylam's RNAi drug vutrisiran demonstrated a 28% reduction in all-cause mortality and recurrent cardiovascular events in ATTR cardiomyopathy patients, with efficacy increasing to 33% in patients not taking Pfizer's tafamidis. • The HELIOS-B trial showed vutrisiran's benefits increased over time, with a 36% reduction in the primary endpoint at 42 months, positioning the quarterly-administered injection as a potential new standard of care. • Vutrisiran, already approved as Amvuttra for ATTR polyneuropathy, could reach multibillion-dollar sales if approved for cardiomyopathy, though it faces competition from BridgeBio's acoramidis and AstraZeneca/Ionis' eplontersen.

The global cardiomyopathy market is expected to grow at a CAGR of 6.13% from 2025-2035, driven by rising cardiovascular disease prevalence and innovative therapeutic developments.