The delay is related to a third-party secondary packaging and labeling facility that Alnylam planned to use for the launch of vutrisiran.
Alnylam (Pavel Kapysh/Shutterstock)
The U.S. Food and Drug Administration has extended the review timeline of Alnylam’s therapeutic vutrisiran to July 14, 2022. The New Drug Application (NDA) was accepted on June 24, 2021, with an initial decision date of April 14.
The three-month extension review period from the FDA is not related to vutrisiran directly. Instead, the delay is related to a third-party secondary packaging and labeling facility that Alnylam planned to use for the launch of vutrisiran. The facility was recently inspected, and the results of the inspection require classification for the FDA to take action on the vutrisiran NDA. To avoid further delays and complications, Alnylam has chosen a new facility for packing and labeling vutrisiran and it has submitted an amendment to the NDA for the FDA’s review.
“We are committed to working with the FDA and the new facility to bring this important treatment option as quickly as possible to patients living with the polyneuropathy of hATTR amyloidosis, an inherited, progressively debilitating and fatal disease,” said Pushkal Garg, M.D., chief medical officer & EVP, development and medical affairs at Alnylam. “We are confident in our regulatory application and the body of data supporting the efficacy and safety of vutrisiran.”
Vutrisiran is intended for the treatment of transthyretin-mediated (ATTR) amyloidosis, a rare, progressive disease characterized by protein misfolding. In those with the condition, transthyretin protein made by the liver misfolds, aggregating in amyloid fibrils that are then deposited in organs, causing systemic symptoms including tendon rupture, lumbar spinal stenosis, palpitations and leg weakness. Notably, the disease causes peripheral sensory-motor neuropathy, autonomic neuropathy and/or cardiomyopathy.
There are two types of ATTR amyloidosis, hereditary, which denotes genetic involvement, and wild-type, which develops with age and is not inherited. Vutrisiran is being developed for both types, with hereditary ATTR amyloidosis representing a major unmet medical need with significant morbidity and mortality.
Vutrisiran is a subcutaneously administered RNA interference (RNAi) therapeutic that targets messenger RNA (mRNA). The drug is designed to target and silence specific mRNA to potentially block the production of both mutant and wild-type TTR protein before it is made, preventing the buildup of amyloid fibrils in the body. Alnylam envisions the therapy being used quarterly or potentially biannually to reduce deposition of misfolded proteins and facilitate the clearance of deposits, hopefully leading to a restoration of organ function.
In January 2022, Alnylam shared positive results from an 18-month study of vutrisiran in patients with hereditary ATTR amyloidosis with polyneuropathy, or the malfunction of peripheral nerves in the body. The drug significantly improved neuropathy impairment, quality of life, gait speed, nutritional status and overall disability in 122 patients. Additionally, vutrisiran performed positively in exploratory cardiac endpoints showing clinically meaningful improvement in patients.
The therapeutic was also well-tolerated and demonstrated an encouraging safety profile with treatment-emergent events occurring in 10% of patients which included pain in extremity, diarrhea and dizziness. The drug caused no clinically significant changes in liver function tests.
Vutrisiran was granted Orphan Drug Designation in the United States and the European Union for the treatment of ATTR amyloidosis. Alnylam submitted a Marketing Authorization Application to the European Medicines Agency in September 2021.
