Complete Response Letter from FDA for supplemental new drug application for patisiran for the treatment of the cardiomyopathy of ATTR amyloidosis

Patisiran is the established name for Onpattro, which is approved by the FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults. The CRL does not pertain to, nor does it impact commercial availability of, Onpattro for this existing indication.

The CRL indicated that the clinical meaningfulness of patisiran’s treatment effects for the cardiomyopathy of ATTR amyloidosis had not been established, and therefore, the sNDA for patisiran could not be approved in its present form. The CRL did not identify any issues with respect to clinical safety, study conduct, drug quality or manufacturing.

As a result of the CRL, the Company will no longer pursue an expanded indication for patisiran in the U.S. The Company remains dedicated to the ATTR amyloidosis community and will continue to focus on the HELIOS-B Phase III study of vutrisiran, an investigational RNAi therapeutic subcutaneously administered once every three months in development for the treatment of the cardiomyopathy of ATTR amyloidosis, and ALN-TTRsc04, which utilizes the Company’s IKARIA technology, with the potential for greater than 90% TTR knockdown with once annual dosing.

“First and foremost, our hearts go out to patients with the cardiomyopathy of ATTR amyloidosis who are living with a rapidly progressive, debilitating and fatal disease and face significant unmet need. While we are disappointed by this decision, we are committed to supporting them and are well positioned to address their needs with continued innovation that can potentially help improve their outcomes and treatment experience,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam Pharmaceuticals. “We remain confident in the HELIOS-B Phase III study of vutrisiran and look forward to sharing topline results in early 2024. If successful, we believe vutrisiran will offer convenient, quarterly subcutaneous dosing with a therapeutic profile that may potentially include cardiovascular outcome benefits. Beyond vutrisiran, we are excited about the potential for ALN-TTRsc04, which may allow for greater TTR knockdown and less frequent dosing, providing patients with ATTR amyloidosis an optimized treatment regimen.”

The sNDA for patisiran was supported by positive results from the APOLLO-B Phase III study. In APOLLO-B, patisiran met the primary endpoint as well as the first secondary endpoint at Month 12, demonstrating a significant difference compared to placebo in functional capacity, as measured by the 6-Minute Walk Test (6-MWT), and health status and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score, respectively.

New results from an interim analysis of the ongoing open-label extension (OLE) period of the APOLLO-B Phase III study were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting (ASM) 2023, which demonstrate the sustained treatment effect of patisiran on functional status, health status and quality of life and cardiac biomarkers over 24 months. These findings reinforce the long-term treatment effect of TTR silencing by an RNAi therapeutic in patients with ATTR amyloidosis and provide strong support for the Company’s continued evaluation of vutrisiran and ALN-TTRsc04.

As previously announced, the FDA’s Cardiovascular and Renal Drugs Advisory Committee met on September 13, 2023 to discuss the sNDA for patisiran and voted 9:3 that the benefits of patisiran outweigh its risks for the treatment of the cardiomyopathy of ATTR amyloidosis. The Company intends to maintain availability of patisiran for patients with the cardiomyopathy TTR amyloidosis who are enrolled in the OLE period of the APOLLO-B Phase III study and patisiran U.S. expanded access protocol (EAP).