Blog November 3, 2017

RNA Interference Achieves Key Milestone with Patisiran Success

It is a not uncommon phenomenon for a new discovery to attract much enthusiasm and hype — as well as investment and new company formation — only to suffer popular disillusionment a few years later as public interest turns to the next hot area of science when clinical success remains elusive and far off. After long years of dogged research and development finally prove the technology’s value in the clinic, excitement often once again blooms as a new class of drugs is launched.  We’ve seen this cycle many times — monoclonal antibodies and gene therapy being well-known examples.  Now, positive results from a Phase 3 trial with Alnylam and Sanofi’s RNA interference (RNAi) treatment patisiran appear likely to support the regulatory approval and commercialization of RNAi drugs as a new therapeutic class in 2018 — and perhaps draw excitement back to this field in general.


The development timeline for RNAi has been a long one — Alnylam was specifically founded in 2002 to pursue therapeutic applications of the technology, and RNAi was the subject of a Nobel Prize for Medicine in 2006. The technology uses bits of genetic code to shut down disease-causing genes and thus treat the disease.


Alnylam has been developing an RNAi drug, patisiran, for the treatment of patients with hereditary ATTR amyloidosis with polyneuropathy, a rare disease that leads to the simultaneous malfunction of many peripheral nerves, causing tingling, numbness, and kidney dysfunction.  In their recently reported Phase 3 study, 225 patients with the disease were enrolled. Two-thirds of the patients received 0.3 mg/kg of the RNAi treatment intravenously once every 3 weeks for 18 months, while the remainder received placebo.


The patisiran-treated patients fared significantly better than the placebo cohort on the trial’s primary endpoint, a modified neuropathy impairment score. They also bested the placebo-treated group in terms of five other secondary trial endpoints, showing a benefit on muscle strength, walking speed, disability, and other relevant disease parameters.  The safety results for the trial were also acceptable, with mild to moderate peripheral edema and infusion-related reactions being the most common adverse events in the treated patients, and discontinuations and deaths reaching higher levels in the placebo-group than those receiving patisiran.  These safety results are significant, as two of Alnylam’s other RNAi drug candidates reported significant problems, including patient deaths, which led to trial discontinuation. RNAi’s development overall has been slow in part due to safety challenges, including off-target effects, and problems related to delivery of these therapeutics.


Based on these positive results, Alnylam intends to seek U.S. approval for patisiran as the first-ever RNAi therapeutic by late 2017 and anticipates an initial market launch by mid-2018. Alnylam plans to commercialize patisiran in U.S., Canada and Western European markets, while Sanofi will market the drug in the rest of the world. Alnylam also hopes to follow its RNAi success with further treatments based on the technology. Givosiran, a potential treatment targeting a rare liver disease, will enter Phase 3 trials before the end of 2017, with interim data expected in mid-2018.


We’ll be awaiting the regulatory decision later this year, in the hopes that this is the first of several RNAi based therapies to come.  What are your thoughts on RNAi technology and its market potential? Do you expect it to succeed and prosper in many other indications or do you think the technology will be overshadowed by CRISPR, if that proves to work? Join our discussion on LinkedIn.