Alnylam hails vutrisiran data, but investors seem sceptical

Alnylam Pharma has been riding high since revealing top-line results from its HELIOS-B trial of vutrisiran in transthyretin-mediated amyloidosis (ATTR) – but a look at the full data seems to have disappointed investors.

Shares in the company retreated after the presentation of the results at the European Society of Cardiology (ESC) conference, which confirmed a 28% reduction in the primary endpoint of deaths from any cause and recurrent cardiovascular events after at least 33 months of follow-up.

The total population also included patients also being treated with Pfizer’s blockbuster ATTR-cardiomyopathy drug Vyndamax (tafamidis meglumine) at baseline, and vutrisiran performed even better if it was used on its own, with a 33% reduction in the primary endpoint.

New data reported at ESC included a 36% reduction in deaths and recurrent cardiovascular events at month 42 for the overall cohort and 35% for the monotherapy group, which accounted for two-thirds of patients in the study. There was also a 22% reduction in those taking vutrisiran and Vyndamax together.

Alnylam’s chief medical officer, Pushkal Garg, said the data “suggest[s] 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.”

The 8.5% fall in the company’s shares – which still leaves the stock well above its level before the top-line data reveal in June – came despite the gene-silencing drug showing a statistically significant improvement on all of the primary and secondary endpoints in HELIOS-B, along with “strong trends” that adding the drug to Vyndamax boosts efficacy.

Vutrisiran is already approved as Amvuttra to treat polyneuropathy caused by ATTR, but extending its indications to include cardiomyopathy is seen as the key to unlocking sales that analysts at Goldman Sachs have suggested could top $5 billion at peak. It made $425 million in the first six months of the year.

Pfizer’s once-daily oral tafamidis therapies Vyndamax and Vyndaqel grew 39% last year to more than $3.3 billion, coming from sales in both ATTR cardiomyopathy and polyneuropathy. Basic patents are, however, due to expire in the US later this year and in Europe in 2026. Pfizer has been working to extend its patent life, but several generic drugmakers have filed copycat versions for approval.

Adding to tafamidis’ efficacy is seen as crucial for vutrisiran as it means the drug – which is administered by physician-administered subcutaneous injection once every three months – can be used both as a monotherapy and combination therapy option, which could be particularly important once cut-price tafamidis generics become available.

One reason for the fall could be the competitive threat posed by BridgeBio’s acoramidis, which demonstrated a 42% reduction in all-cause mortality and recurrent cardiovascular events in its phase 3 ATTRibute-CM trial and could be approved by the FDA in November. Shares in BridgeBio rose 13% after the ESC presentation.

Another potential rival is AstraZeneca and Ionis’ Wainua (eplontersen) – which is administered by self-injection every three months and is already approved for ATTR polyneuropathy. It is in the CARDIO-TTRansform study in ATTR cardiomyopathy, with results due next year.

HELIOS-B principal Investigator Professor Marianna Fontana, of University College London and the Royal Free Hospital in the UK, who presented the data at ESC, said: “Vutrisiran was highly effective and well tolerated in this contemporary population representative of patients that we see in our clinics, with consistent benefits regardless of background tafamidis therapy.”

She added: “This trial is also important as it is the first to show the benefit of gene silencers in any type of cardiomyopathy.”