Alnylam's Another RNAi Therapy Gets FDA Fast Track Qualification

- Apr 09, 2020-

Alnylam recently announced that the US FDA has granted vutrisiran fast-track qualification (FTD), a research RNAi therapy for the treatment of polyneuropathy caused by hereditary transthyretin protein (hATTR) amyloidosis in adults.


FTD aims to accelerate the development and rapid review of drugs for serious diseases to address serious unmet medical needs in key areas. Obtaining FTD for research drugs means that pharmaceutical companies can interact with the FDA more frequently during the R & D phase. After submitting a marketing application, they are eligible for accelerated approval and priority review if they meet the relevant standards. In addition, they are also eligible for rolling review.


In addition to being granted FTD, vutrisiran has also been granted orphan drug status (ODD) for the treatment of ATTR amyloidosis in the United States and the European Union. Currently, Alnylam is conducting two phase III clinical trials (HELIOS-A, HELIOS-B) to evaluate the safety and effectiveness of vutrisiran. Together, these studies constitute a comprehensive clinical development project aimed at demonstrating that vutrisiran has a wide-ranging impact on the multi-system manifestations of the disease and the full spectrum of patients with ATTR amyloidosis.


In the HELIOS-A study, 164 patients were randomly assigned to receive vutrisiran or Onpattro, with the aim of proving whether vutrisiran is superior to Onpattro in treating nerve damage. In the HELIOS-B study, 600 patients with hATTR amyloidosis with cardiomyopathy were randomly assigned to receive vutrisiran or placebo to assess the impact of vutrisiran on all-cause mortality and hospitalization rates associated with cardiovascular disease. Data from these two studies is expected to be obtained in early 2021.


Vutrisiran is a research-based, subcutaneous injection of RNAi therapy for the treatment of ATTR amyloidosis, including hereditary and wild-type amyloidosis. The drug is designed to target and silence specific messenger RNA and block it before wild-type and mutant transthyretin (TTR) proteins are produced. Vutrisiran is injected subcutaneously every quarter, which will help reduce the deposition of TTR amyloid in tissues, promote their removal and restore the function of these tissues. Vutrisiran used Alnylam's next-generation delivery platform-Enhanced Stability Chemistry (ESC)-GalNAc conjugate delivery platform development. If approved, it will further strengthen Alnylam's leading position in the hATTR amyloidosis treatment market.


Alnylam is a leader in the development of RNAi therapies. Its first product, Onpattro (patisiran), was approved by the FDA in August 2018, becoming the first RNAi drug to be approved for marketing in the 20 years since the RNAi phenomenon was discovered. In November 2019, the company's other drug, Givlaari (givosiran), was approved by the FDA for use in adult patients with acute hepatic porphyria (AHP) and became the second RNAi drug in the world.


Currently, Alnylam has two other RNAi therapies under review by regulatory agencies, and both are expected to be approved for listing this year. One of them is lumasiran, used to treat primary hyperoxaluria type 1 (PH1); the other is inclisiran, used to treat hypercholesterolemia. In addition, there are 6 RNAi therapies in the company's pipeline that are in late clinical development.


Prior to this, TMC and Alnylam signed a licensing and cooperation agreement to obtain the global development and commercialization rights of inclisiran. In November 2019, Novartis acquired TMC for US $ 9.7 billion and included inclisiran. Based on the agreement, Alnylam is eligible to receive inclisiran tiered royalties of up to 20% of global sales from Novartis.


Currently, there are two cholesterol-lowering drugs targeting PCSK9 on the market, but they need to be administered every 2 weeks or monthly. Inclisiran is administered once every 6 months and only twice a year, which is very advantageous in terms of treatment convenience. EvaluatePharma, a pharmaceutical market research agency, predicts that the annual sales peak of inclisiran will reach US $ 2.6 billion after its listing. Before Inclisiran's patent expires in 2035, Alnylam was able to obtain royalties from Novartis totaling more than $ 2.2 billion.


It is worth mentioning that just two days ago, Blackstone Group and Alnylam reached a strategic partnership. In this collaboration, Blackstone will provide $ 2 billion in funding to help Alnylam advance technological innovation and accelerate the commercialization process. Alnylam stated that the cooperation will help Alnylam "achieve financial sustainability without refinancing."