Alnylam’s vutrisiran aces ATTR cardiomyopathy readout

Alnylam is riding high today after reporting its RNAi drug vutrisiran showed across-the-board efficacy in cardiomyopathy associated with transthyretin-mediated amyloidosis (ATTR), setting up regulatory filings.

The announcement of top-line data from the HELIOS-B study sparked a 36% increase in Alnyam’s share price in pre-market trading as investors looked forward to a new revenue stream for the drug, which is already approved as Amvuttra to treat polyneuropathy caused by ATTR. The size of the increase suggests the results exceeded investors’ expectations. 

In the trial, vutrisiran given on its own reduced the risk of all-cause mortality and recurrent cardiovascular (CV) events by 28% after 36 months compared to placebo in the overall population, which included patients also being treated with Pfizer’s blockbuster ATTR-cardiomyopathy drug Vyndamax (tafamidis meglumine) at baseline.

The drug reduced the primary endpoint by an even more impressive 33% in a subgroup of patients who had not been on Pfizer’s drug at the start of the trial, and also reduced all-cause mortality by around 35%.

Additionally, it hit the mark on a range of secondary endpoints, showing improvement over placebo on the 6-minute walk test (6-MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and New York Heart Association (NYHA) Class.

Alnylam’s chief executive, Yvonne Greenstreet, said that vutrisiran has the potential to be a “transformative medicine” for ATTR-cardiomyopathy that could become a new standard of care, “driving Alnylam’s next era of substantial growth.”

The optimism behind the drug is evident in the fact that Alnylam has decided to use a priority review voucher (PRV) to reduce the FDA’s deliberation time for the upcoming marketing application to six months. 

The market for ATTR therapies is very large, with Pfizer’s tafamidis-based products Vyndamax and Vyndaqel (tafamidis) growing 39% last year to more than $3.3 billion. The oral, daily-administered drug is approved for both ATTR cardiomyopathy and polyneuropathy. 

Vutrisiran, meanwhile, is administered by physician-administered subcutaneous injection once every three months and brought in sales of $558 million last year from its use in ATTR-polyneuropathy alone. Alnylam thinks it could get approved for cardiomyopathy early next year, and reckons that could unlock “multibillion-dollar” potential sales.

For a rough comparison, Pfizer’s drug achieved a 41% reduction in all-cause mortality with five years of follow-up in the ATTR-ACT trial, having shown a 30% reduction at the 30-month timepoint, suggesting that vutrisiran is showing at least a similar benefit. 

The first patents on tafamidis are due to expire later this year, which could lead to generic competition, although Pfizer has filed lawsuits trying to fend off potential rivals until other patents expire, in one case extending out to 2035. 

Meanwhile, other rivals are now on or near the market, notably AstraZeneca and Ionis’ Wainua (eplontersen), which was approved by the FDA for ATTR-polyneuropathy in December and is also being developed for ATTR-cardiomyopathy. It can be self-administered by injection once a month.