the company has announced.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
In September, the FDA Cardiovascular and Renal Drugs Advisory Committee voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy on the basis of the results of the APOLLO-B phase 3 study.
However, many panel members questioned whether the benefits are clinically meaningful – a view shared by the FDA in a complete response letter (CRL) the FDA sent to Alnylam.
According to the company, the FDA indicated in the letter that the clinical meaningfulness of patisiran’s treatment effects for the cardiomyopathy of ATTR amyloidosis have “not been established,” and therefore, the supplemental new drug application for patisiran “could not be approved in its present form.”
The FDA did not identify any issues with respect to clinical safety, study conduct, drug quality, or manufacturing.
Nonetheless, as a result of the CRL, the company said it will no longer pursue an expanded indication for patisiran in cardiomyopathy of ATTR amyloidosis in the United States.
The company said it will continue to make patisiran available for patients with cardiomyopathy of ATTR amyloidosis who are enrolled in the open-label extension period of the APOLLO-B study and the patisiran expanded access protocol.
The company also said it will continue to focus on the HELIOS-B phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of cardiomyopathy of ATTR amyloidosis.
“We remain confident in the HELIOS-B phase 3 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,” Alnylam CEO Yvonne Greenstreet, MBChB, said in the statement.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of polyneuropathy of hereditary ATTR amyloidosis in adults.
A version of this article first appeared on Medscape.com.