FDA OKs Patisiran (Onpattro) for Polyneuropathy in hAATR

Megan Brooks

August 10, 2018

The US Food and Drug Administration (FDA) has approved patisiran (Onpattro, Alnylam Pharmaceuticals Inc) for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adults.

Patisiran is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs. Patisiran is also the first of a new class of targeted RNA-based therapies to treat a rare disease, the FDA said.

Patisiran, which is administered intravenously, uses RNA interference to interfere with production of mutant transthyretin (TTR) protein. By preventing the production of TTR, the drug can help reduce the accumulation of amyloid deposits in peripheral nerves, improving symptoms and helping patients better manage the condition, the FDA said.

Until now, treatment options for hATTR, which affects around 50,000 people worldwide, have generally focused on symptom management.

"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. 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," FDA Commissioner Scott Gottlieb, MD, said in a news release.

The efficacy of patisiran was demonstrated in APOLLO, a clinical trial involving 225 patients: 148 randomly allocated to receive an infusion of patisiran once every 3 weeks for 18 months and 77 to receive a placebo infusion at the same frequency.

The results were presented in April at the American Academy of Neurology 2018 Annual Meeting.

As reported by Medscape Medical News, patisiran led to significant improvement in polyneuropathy, including muscle strength, sensation (pain, temperature, numbness), reflexes, and autonomic symptoms (blood pressure, heart rate, digestion), from baseline relative to placebo.   

There were also significant improvement in quality of life, reduction in disease symptoms and disability, and improvement in ambulation with treatment vs placebo. Favorable changes in exploratory cardiac measures were also seen in the subpopulation of patients with good safety and tolerability.

Results of a post hoc analysis showed about a 50% reduction in the composite rate of all-cause hospitalization and mortality and a 45% reduction in the composite rate of cardiac hospitalization and all-cause mortality.

The FDA notes that the most common adverse reactions reported by patients treated with patisiran are infusion-related reactions, including flushing, back pain, nausea, abdominal pain, dyspnea,  and headache. All patients who participated in the clinical trials received premedication with a corticosteroid, acetaminophen, and antihistamines (H1- and H2-blockers) to reduce the occurrence of infusion-related reactions.

Patients may also experience vision problems, including dry eyes, blurred vision, and vitreous floaters. Patisiran leads to a decrease in serum vitamin A levels, so patients should take a daily vitamin A supplement at the recommended daily allowance, the FDA advises.

Patisiran had fast track, priority review and breakthrough therapy status, as well as orphan drug designation.

"There has been a long-standing need for a treatment for hereditary transthyretin-mediated amyloidosis polyneuropathy. This unique targeted therapy offers these patients an innovative treatment for their symptoms that directly affects the underlying basis of this disease," Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, said in the release.

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