Alnylam’s success brings first RNAi therapeutic to US

The US Food and Drug Administration (FDA) has approved the first ever RNA interference (RNAi) therapy: Alnylam’s Onpattro (patisiran).

Alnylam announced last week Onpattro has been approved in the US for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The product was hailed by the FDA as the first in a new class of drugs: small interfering ribonucleic acid (siRNA) treatments.

“New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses,” said FDA commissioner Scott Gottlieb. “We’re committed to advancing scientific principles that enable the efficient development and review of safe, effective and groundbreaking treatments that have the potential to change patients’ lives.”

Onpattro works by silencing a portion of RNA involved in producing an abnormal form of the protein transthyretin (TTR). It uses Alnylam’s Lipid Nanoparticle (LNP) technology platform to deliver the drug directly into the liver.

hATTR is a rare condition, affecting about 50,000 people worldwide. The drug’s average list price – which doesn’t include rebates to insurers — is US$450,000 (€395,000) per patient, per year, Xconomy reported. The average net price, taking rebates into account, is $345,000 per year.

Onpattro received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) late last month, paving the way for approval in Europe.

Alnylam holds the commercialization rights to Onpattro in the US, Canada and Western Europe, while Sanofi Genzyme holds the rights in the rest of the world, following a $700 million deal in 2014, which also saw Sanofi take a stake in Alnylam.

RNAi manufacturing

Alnylam stated the first batches of Onpattro are already available.

The firm has a facility in the southeastern Massachusetts town of Norton, which it built for $200 million in 2016 to support its clinical and commercial drug products, including siRNAs (small interfering RNA) and siRNA conjugates.

However, earlier this year, Alnylam entered into a five-year manufacturing services agreement for commercial supply of patisiran drug substance with Agilent Technologies. Agilent has a 69,000 sq ft GMP commercial API facility located in Boulder, Colorado.