Patisiran Infusion Approved as First-Ever Therapy for Polyneuropathy Caused by hATTR

The US Food and Drug Administration (FDA) has approved patisiran (Onpattro) infusion for the treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. With the approval, the therapy becomes the first indicated for the disease caused by hATTR—a rare, potentially fatal genetic disease characterized by abnormal amyloid protein buildup.

Patisiran also makes history as the first FDA-approved small interfering ribonucleic acid (siRNA) treatment, a class of drugs that “silences” the portion of RNA involved in causing the disease. The patisiran infusion provides direct action against the proteins by encasing siRNA into a lipid nanoparticle to deliver the drug directly into the patient’s liver.

The therapy was particularly designed to interfere with the RNA production of an abnormal form of the protein transthyretin (TTR), thereby reducing amyloid deposit accumulation in peripheral nerves and improving patient symptoms.

Investigators reported the efficacy of patisiran in a clinical trial involving 225 patients—148 (65.7%) of whom were randomly assigned to the infusion therapy once every 3 weeks over 18 months, and 77 (34.3%) of whom were randomly assigned to placebo infusion at the same dosing regimen.

Patients on patisiran reported better polyneuropathy-based symptom outcomes in measures of muscle strength, sensation, reflexes, and autonomic symptoms versus patients on placebo. They also scored better on measures of walking, nutrition, and capability of performing daily activities.

Patisiran-treated patients most commonly reported infusion-related adverse reactions, such as flushing, back pain, nausea, abdominal pain, dyspnea, and headache. However, all participating patients received corticosteroid, acetaminophen, and anithistamines prior to their therapy, in order to account for any infusion-related reactions.

The FDA had granted the Alnylam Pharmaceuticals application Fast Track, Priority Review, and Breakthrough Therapy designations, as well as an Orphan Drug designation.

In a statement addressing the approval, FDA commissioner Scott Gottlieb, MD, said the approval is part of a “broader wave of advances” that directly target the root cause of a disease in order to stop or reverse the condition.

“In this case, the effects of the disease cause a degeneration of the nerves, which can manifest in pain, weakness and loss of mobility,” Gottlieb said. “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.”

In an interview with MD Magazine® sister publication Rare Disease Report®, Morie Gertz, MD, chair of Internal Medicine, Minnesota, at Mayo Clinic, called patisiran a practice-changing drug.

“In the US, the only approved treatment for hereditary TTR amyloidosis has been liver transplantation, which is very resource intensive, is limited by donor availability, is still associated with the potential for progressive disease, and now for the first time in this patient population, alternatives are available, and it’s certainly simpler than liver transplantation,” Gertz said. “In reality, it’s the first medication approved in the US for the treatment of hereditary TTR amyloidosis, at least at this time.”

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