he Food and Drug Administration on Friday approved a landmark rare disease treatment — the first to rely on a Nobel-prize-winning technique known as RNA interference, which silences disease-causing genes.

The approval is a major accomplishment for Cambridge, Mass.-based Alnylam, which will be marketing the drug, patisiran, as Onpattro and which has been working to bring an RNAi-based therapy to market for more than a decade.  

The agency gave patisiran a relatively narrow green light. Its only indication is for neuropathy, or nerve damage. Unlike the European regulator’s initial opinion, the FDA’s press release announcing the approval made no mention of Onpattro’s possible effect on heart damage, which is also a common symptom of the disease, known as hereditary transthyretin amyloidosis, or hATTR.


“Until today, there were no approved medications to treat these patients in the United States,” Alnylam CEO John Maraganore said on a conference call Friday afternoon. “We do look forward to working with the FDA to expand the Onpattro label in the future.”

It also does not specifically reference the form of the disease that is not inherited, though Alnylam executives have suggested that condition could be a focus for the company in the future.

“This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms,” FDA Commissioner Scott Gottlieb said in a press release announcing the approval.

The annual average list price for patisiran will be $450,000 — which is within the broad six-figure range that analysts had predicted. But the cost is higher than what the Institute for Clinical and Economic Review had assumed for a draft report, which concluded the drug would not be cost-effective at a price of $300,000 or higher. (The drug’s estimated price with discounts — $345,000 — is slightly closer to that number.) Maraganore has disagreed with the methodology of that report.

Alnylam said it plans to establish a value-based reimbursement model for the drug with “major health insurers”—essentially issuing a money-back guarantee if the drug doesn’t work for someone as well as it did in clinical trials. The company declined to provide any sales estimates in a conference call following the approval.

Patisiran may be the first RNAi-based drug on the market, but it won’t be the only one. Alnylam alone has three other late-stage RNAi-based drug candidates: givosiran for porphyrias, inclisiran to treat high cholesterol, and fitusiran for hemophilia. (Until December, fitusiran was on a clinical hold because a patient died.)

Once Alnylam launches Onpattro, the company itself won’t be manufacturing it. Agilent Technologies will be supplying it for the next five years. In time, patisiran production may shift to a manufacturing plant Alnylam is building in Norton, Mass. The facility should be ready by late 2019 or early 2020. 

The drug may be shipped out to health care providers by Sunday afternoon, a press release from Alnylam stated.

Alnylam shares were halted at $97 for most of the afternoon but fell 5 percent to $93 when trading re-opened. Investors had hoped for a broader FDA label that would have allowed Alnylam to market the drug to a bigger group of patients.

Correction: An earlier version of this story misstated which Alnylam products are in the late stage of development. Lumasiran is an early-stage candidate.

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