The FDA today granted Alnylam Pharmaceuticals approval for a first-in-class small interfering ribonucleic acid (siRNA) treatment—the first therapy indicated for polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults.

Onpattro™ (patisiran) is an infusion treatment whose approval comes 20 years after the discovery of RNA interference. Onpattro is designed to interfere with RNA production of an abnormal form of the protein transthyretin (TTR). By preventing the production of TTR, the drug is intended to help reduce the accumulation of amyloid deposits in peripheral nerves, improving symptoms and helping patients better manage their polyneuropathy.

“Alnylam was founded on the vision of harnessing the potential of RNAi therapeutics to treat human disease, and this approval heralds the arrival of an entirely new class of medicines,” Alnlyam CEO John Maraganore, Ph.D., said in a statement. “We believe today draws us ever-closer to achieving our Alnylam 2020 goals of becoming a fully integrated, multi-product biopharmaceutical company with a sustainable pipeline.”

Alnylam is one of several companies that have pursued development of RNAi treatments in recent years. Arrowhead Pharmaceuticals, for example, is in clinical phases of developing RNAi candidates ARO-HBV for hepatitis B and ARO-AAT for the liver disease associated with alpha-1 antitrypsin deficiency.

In June, Akcea Therapeutics won approval in Europe for Tagsedi (inotersen) for stage 1 or stage 2 polyneuropathy in adult patients with hATTR. Tegsedi is under FDA review with a target PDUFA decision date of October 6.

hATTR is a rare disease that affects about 50,000 people worldwide, characterized by the buildup of amyloid in the body's organs and tissues that interferes with their normal functioning. Most frequently, the protein deposits most occur in the peripheral nervous system, which can result in a loss of sensation, pain, or immobility in the arms, legs, hands, and feet. Amyloid deposits can also affect the functioning of the heart, kidneys, eyes, and gastrointestinal tract. Treatment options have generally focused on symptom management.

“Part of a Broader Wave”

“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, M.D., said in a statement. “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.”

Onpattro acts to alter or halt the production of hATTR-causing proteins by encasing its siRNA into a lipid nanoparticle, enabling it to deliver the drug directly into the liver.

During a conference call with analysts this afternoon, Alnylam said it plans to charge a list price of $450,000 per year for the averaghe patient for Onpattro, which will be dosed according to a patient's weight, but added that the price to patients after discounts will be $345,000.

Alnylam also said it had reached agreement in principle on the structure of value-based agreements with Harvard Pilgrim Health Care and other unidentified “major” health insurers, with discussions ongoing with many others.

To broaden patient access to Onpattro, Alnylam said, it has also launched launched Alnylam Assist, a program consisting of personalized services that include access to in-house case managers to assist in verifying insurance benefits and financial support for eligible patients, and field-based liaisons wose work will entail educating patients on hATTR amyloidosis.

The FDA approved Onpattro based on positive results from the global Phase III APOLLO study, results of which were published July 5 in the New England Journal of Medicine. The randomized, double-blind, placebo-controlled APOLLO was the largest-ever study in hATTR amyloidosis patients with polyneuropathy. APOLLO enrolled 225 hATTR amyloidosis patients in 19 countries with 39 genotypes who were randomized 2:1 (Onpattro:placebo) with patisiran administered at 0.3 mg/kg intravenously once every 3 weeks for 18 months.

APOLLO results showed that Onpattro improved measures of polyneuropathy, quality of life, activities of daily living, ambulation, nutritional status, and autonomic symptoms relative to placebo in patients with hATTR amyloidosis. Treatment with Onpattro also led to favorable effects on exploratory endpoints related to cardiac structure and function in patients with cardiac involvement, Alnylam said last month.

The most common adverse reactions reported by patients treated with Onpattro were infusion-related reactions including flushing, back pain, nausea, abdominal pain, dyspnea (difficulty breathing) and headache.

The FDA granted Onpattro its Fast Track, Priority Review Breakthrough Therapy, and Orphan Drug designations.

Previous articleCould Glaucoma Be an Autoimmune Disease?
Next articleWhat the Top 10 Biopharma CEOs Are Making