Alnylam joins three-way contest in ATTR cardiomyopathy

Alnylam has the FDA approval it sought for Amvuttra in a form of cardiomyopathy associated with rare disease ATTR amyloidosis (ATTR-CM), allowing it to compete head-to-head with rival therapies from Pfizer and BridgeBio Pharma.

Amvuttra (vutrisiran) has become the first RNA interference therapy to be approved for ATTR-CM, and the second challenger to Pfizer's Vyndaqel/Vyndamax (tafamidis) – which became the first drug for the disorder in 2019 – alongside BridgeBio's Attruby (acoramidis), which got an FDA green light last November.

Alnylam's drug has been approved to treat polyneuropathy associated with ATTR since 2022, bringing in sales of $970 million last year. Analysts consider, however, that the more life-threatening cardiomyopathy indication could catapult the drug to multibillion-dollar annual sales and make the company reliably profitable for the first time.

Part of the optimistic appraisal of its prospects comes from the strong results seen in the HELIOS-B study, in which Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular (CV) events by 28% after 36 months compared to placebo.

That result included a broad ATTR-CM population that included patients also being treated with Vyndamax at baseline and – if that group was excluded – Amvuttra performed even better with a 33% reduction in all-cause mortality and recurrent CV events, as well as a 35% improvement in survival.

With the usual caveat of trying to make comparisons between studies using different protocols and patient populations, Pfizer achieved a 41% reduction in all-cause mortality with five years of follow-up with tafamidis, while Attruby managed a 25% reduction in all-cause mortality at 30 months.

Despite being a rare disease, the market for ATTR therapies is large. Pfizer's products – both oral therapies for ATTR-CM – brought in $5.45 billion in revenues last year. Meanwhile, orally-dosed Attruby arrived too late onto the market last year to generate a sales figure, although, BridgeBio has reported that initial take-up was strong, with more than 1,000 prescriptions written by the end of 2024.

Amvuttra in comparison is given as a physician-administered subcutaneous injection once every three months, and the jury is out on whether its route of administration will be a help or hindrance to take-up.

On a conference call, Alnylam said that it intended to price the drug at $464,000 ($119,000 per prefilled syringe) – in line with what is charged for ATTR-PN – but said that would be reduced as patient numbers increased. For comparison, Pfizer and BridgeBio therapies have list prices in the region of $250,000.

Alnylam clearly has high hopes for Amvuttra in ATTR-CM, as it used a priority review voucher (PRV) – which has a market value of around $100 million if sold – to speed up the FDA's review, and has said it expects combined sales of the drug and older ATTR therapy Onpattro (patisiran) to reach up to $1.7 billion this year.