Alnylam's Onpattro clears FDA vote for ATTR-cardiomyopathy
Despite a sceptical appraisal by FDA reviewers, Alnylam's Onpattro has been recommended for approval as a treatment for transthyretin amyloidosis cardiomyopathy (ATTR-CM) by the regulator's advisors.
The expert panel voted by nine to three that the benefits of Onpattro (patisiran) outweigh its risks as a treatment for ATTR-CM, a disease characterised by the formation of amyloid fibril deposits in the heart, ahead of a final FDA decision expected by 8th October.
Their positive assessment comes after the FDA reviewers published a briefing document ahead of the meeting, poking holes in the data for the drug in ATTR-CM, which comes mainly from the phase 3 APOLLO-B study.
In that trial, Onpattro met the primary endpoint of a statistically significant improvement in functional capacity, as measured by the 6-minute walk test (6-MWT), compared to placebo, with patients on the drug able to walk almost 15 metres further than the control group at 12 months.
It also met secondary objectives, showing improvements in health status and quality of life compared to placebo. However, the FDA said in its briefing document that the differences between the drug and placebo were "small" and raised "questions about its clinical meaningfulness."
It also noted that there seemed to be no benefit for Onpattro when used with Pfizer's Vyndamax (tafamidis), a widely-used therapy for ATTR-CM. Around 25% of patients on Onpattro in the study were also taking the Pfizer drug.
Onpattro was the first RNA interference drug to be approved by the FDA, getting the green light for polyneuropathy associated with hereditary ATTR in 2018, and is Alnylam's top-selling drug, adding $588 million to its top line last year.
The company's chief medical officer, Pushkal Garg, said that the advisory committee vote is "another step towards bringing patients with the cardiomyopathy of ATTR amyloidosis a novel treatment option that addresses the underlying cause of disease and has the potential to meaningfully benefit patients' functional capacity and quality of life."
Overall, panellists seemed to acknowledge that Onpattro had modest efficacy in ATTR-CM, but were tipped in favour of approval as the drug has a well-documented and manageable safety profile.
If the FDA clears the RNAi for the new indication, it will be a competitor to Vyndamax and Vyndaqel (tafamidis meglumine), which had worldwide sales of $2.5 billion last year.
Also coming through the pipeline is BridgeBio's acoramidis, which missed the mark on the 6MWT measure in the phase 3 ATTRibute-CM trial, but recovered with a significant benefit in a compositive endpoint that included all-cause mortality and cardiovascular-related hospitalisation.