Acoramidis

With last week's FDA approval of Attruby (acoramidis), BridgeBio may reach transthyretin amyloid cardiomyopathy (ATTR-CM) patients first, but Alnylam isn't far behind. The company used a priority review voucher as part of its regulatory submission for RNAi therapeutic vutrisiran, which the US regulator accepted on Monday and granted a PDUFA date of March 23, 2025. BridgeBio and Alnylam are both vying for a piece of the ATTR-CM market, which Pfizer currently dominates. The pharma's tafamidis — marketed as Vyndamax and Vyndaqel — became the first drug approved for the rare heart disease in 2019, and last year brought in a total of $3.3 billion in global sales. While BridgeBio's Attruby, an oral TTR stabiliser, has the same mechanism of action as tafamidis, Alnylam's asset is a wholly separate modality. Vutrisiran is designed to deliver rapid knockdown of mutant and wild-type transthyretin (TTR), the disease's underlying cause. The RNAi therapeutic was approved in 2022 as Amvuttra to treat polyneuropathy in adults with hereditary transthyretin-mediated (hATTR) amyloidosis.ATTR anticipationCardiologists have been excited about vutrisiran's potential in ATTR-CM since Alnylam top-lined data from the Phase III HELIOS-B trial in June.  In the overall study population, vutrisiran reduced all-cause mortality and recurrent cardiovascular events by 28% compared to placebo (see – Physician Views Results: Cardiologist feedback suggests Alnylam well placed to take on Pfizer in ATTR-CM field).Further results from HELIOS-B shared in August at the European Society of Cardiology (ESC) congress demonstrated that in the overall study population, vutrisiran reduced the relative risk of death by 31% through month 36, and by 36% after up to 42 months. However, patients not receiving tafamidis at the trial's start saw a non-significant risk reduction of 30% at 36 months. After the data drop, FirstWord spoke with Sarju Ganatra, director of the Cardio-Oncology Programme and co-director of the South Asian Cardio-Metabolic Programme at Lahey Hospital and Medical Center, who said the monotherapy arm showed a "lacklustre performance on the mortality benefit." For the full interview, see KOL Views Q&A: HELIOS-B cements pecking order for Alnylam’s Amvuttra, Pfizer’s Vyndamax in ATTR-CM.A pair of physician polls conducted after the ESC presentation showed that vutrisiran is on track to become an important new treatment option for ATTR-CM, though the majority of cardiologists noted that it was likely to be used most frequently alongside other treatment options (see Physician Views Poll Results: Amvuttra another compelling treatment option for ATTR-CM, say majority of cardiologists and Physician Views Results: Cardiologists have much to ponder with ATTR-CM treatment options set to expand).Meanwhile, Alnylam also has next-generation siRNA therapeutic nucresiran in early-stage testing for ATTR. The drug recently demonstrated rapid and durable reduction of serum TTR in healthy participants.

The US Food and Drug Administration (FDA) has approved BridgeBio Pharma’s Attruby (acoramidis) to treat adults with transthyretin amyloid cardiomyopathy (ATTR-CM) . The orally-administered drug has been specifically authorised to reduce cardiovascular death and cardiovascular-related hospitalisation in patients with the rare heart disease. Affecting up to 500,000 people worldwide, ATTR-CM is a progressive condition that occurs when the transthyretin (TTR) protein becomes misshapen and builds up in the heart. These deposits can lead to heart failure, making it difficult for the heart to pump blood properly. Attruby is designed to mimic a naturally occurring “rescue mutation” of the TTR gene that targets the root cause of ATTR-CM and, following the FDA’s approval, Attruby is now the first and only approved product with a label specifying near-complete stabilisation of TTR. The US regulator’s decision on the drug was supported by positive results from the late-stage ATTRibute-CM trial of 632 patients with symptomatic ATTR-CM. Results showed that Attruby significantly improved survival and reduced cardiovascular-related hospitalisation after 30 months of treatment compared to placebo. Kristen Hsu, executive director of research at the Amyloidosis Research Consortium, described the authorisation as a “significant milestone” for patients. “This new therapy provides more choices for patients and healthcare providers, helping to better manage this challenging disease. We’re hopeful that Attruby will improve outcomes and bring greater hope to those living with ATTR-CM,” she said. BridgeBio’s founder and chief executive officer, Neil Kumar, said the company’s “journey [with Attruby] is not over as [it looks] to pursue approvals globally, next in Europe, Japan and Brazil, and to continue exploring the full potential of this treatment”. Bayer has an exclusive licence to commercialise acoramidis for ATTR-CM in Europe, while AstraZeneca’s rare disease unit Alexion maintains an exclusive licence for the asset in Japan. Earlier this year, AstraZeneca shared positive phase 3 results that showed consistency with those in ATTRibute-CM, including survival, cardiac-related hospitalisations and other measures of improved functions and quality of life at 30 months.