FDA approves first RNA-based therapy for treatment of rare hereditary disease

The US Food and Drug Administration (FDA) has approved the first RNA-based therapy for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated (hATTR) amyloidosis in adults.

Onpattro (patisiran) from Alnylam Pharmaceuticals is a lipid complex injection, RNA interference (RNAi) therapeutic aimed at the treatment of hATTR amyloidosis — a rare, inherited, rapidly progressive and life-threatening disease with multiple manifestations.

This approval marks not only the first of a treatment for patients with polyneuropathy caused by hATTR but also the first approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.

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

“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. 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,” stated John Maraganore, PhD, chief executive officer of Alnylam. “With the potential for the sequential launches of several new medicines in the coming years, we believe we have the opportunity to meaningfully impact the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs.”

“Today’s historic approval marks the arrival of a first-of-its kind treatment option for a rare and devastating condition with limited treatment options,” added Dr Akshay Vaishnaw, PhD, president of R&D at Alnylam. “We extend our deepest gratitude to the patients who participated in the Onpattro clinical trials and their families and caregivers who supported them. We are also grateful for the tireless efforts of the investigators and study staff, without whom this important milestone would not have been possible. We also look forward to working with the FDA to potentially expand the Onpattro indication in the future.”

The approval was based on positive results from the Phase III study (APOLLO) — a randomised, double-blind, placebo-controlled, global study evaluating the safety and efficacy of Onpattro in patients with hATTR amyloidosis. It was found that Onpattro improved measures of polyneuropathy, quality of life, activities of daily living, ambulation, nutritional status and autonomic symptoms when compared with placebo.

“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,” commented Dr Billy Dunn, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.