With patisiran FDA nod imminent, Alnylam preps CNS pipeline for the clinic

John Maraganore
Alnylam plans to select its first CNS candidate this year and file its first IND in late 2019 or early 2020. (Alnylam)

On the back of promising preclinical data, Alnylam is gearing up to move RNAi therapies for central nervous system disorders into the clinic. The biotech is looking to tackle neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's, that have so far eluded effective treatment, planning to file its first IND by early 2020.

The company presented data (PDF) Tuesday at the TIDES: Oligonucleotide and Peptide Therapeutics annual meeting showing that a single, intrathecal injection successfully delivered a small interfering RNA (siRNA) conjugate to the brain and spinal cord. The data demonstrated "robust, durable, and broadly distributed silencing of CNS gene transcripts," the company said in a statement.

Alnylam plans to select its first CNS candidate this year and file its first IND in late 2019 or early 2020, "with the potential for one or more INDs per year thereafter." In addition to ALS and Alzheimer's, the company identified Parkinson's and Huntington disease as areas of unmet need that are "well-suited" for RNAi therapies.

"As we begin to advance our CNS pipeline, initial efforts are focused on genetically validated CNS targets, use of biomarkers for initial proof-of-concept, and disease settings with high unmet need and a definable path to regulatory approval and patient access,” said Kevin Fitzgerald, Ph.D., SVP of research at Alnylam.

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It's a big year for the RNAi player, which is poised to take its first RNAi treatment to market after spending the first 15 years of its life in R&D mode. The FDA's PDUFA date for the hereditary ATTR amyloidosis drug patisiran is Aug. 11, and the agency does not expect to hold an advisory committee meeting for the NDA.

Alnylam retooled its RNAi collaboration with Sanofi in January to regain the global rights to patisiran, as well as those to its early-stage candidate ALN-TTRsc02, while Sanofi will pick up the global rights for fitusiran. The deal, originally struck in 2014, had Alnylam ceding to Sanofi the rights to patisiran outside of North America and Western Europe.

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Sanofi decided not to opt into Alnylam’s primary hyperoxaluria type 1 (PH1) drug lumasiran in March, but not long after, Alnylam inked a discovery deal with Regeneron around RNAi treatments for chronic liver disease nonalcoholic steatohepatitis (NASH), and potentially for other diseases too.