“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,” Akshay Vaishnaw, Alnylam’s president of research and development, said in a press release.
FAP, also known as hereditary ATTR amyloidosis, is caused by mutations of the transthyretin (TTR) gene that lead to the production of faulty TTR proteins, which form toxic amyloid deposits in tissues.
Onpattro, an RNA interference (RNAi) therapy, is designed to prevent the production of the abnormal form of TTR by blocking its messenger RNA strand, the molecule generated from the mutated TTR gene that contains the instructions to produce the faulty TTR protein.
By preventing the production of abnormal TTR, the therapy can help reduce the accumulation of amyloid deposits in peripheral nerves and ease FAP-related symptoms.
The randomized, placebo-controlled, multi-center APOLLO study evaluated the safety and effectiveness of Onpattro in adults with FAP. It enrolled 225 FAP patients from 19 countries who were randomized to receive either Onpattro (148 patients) or placebo (77 patients) infusions (directly into the bloodstream), once every three weeks for 18 months.
APOLLO results showed that Onpattro safely and robustly decreased the levels of TTR protein and eased FAP-related symptoms, reflected by improved measures of polyneuropathy — with reversal of neuropathy impairment in 56 percent of patients — including muscle strength, reflexes, sensation (pain, numbness, and temperature), and autonomic parameters (blood pressure, heart rate, and digestion), compared with placebo.
Patients receiving Onpattro also showed greater improvements in their quality of life, ability to perform activities of daily living, walking ability, and nutritional status, compared with those receiving placebo.
The most common adverse effects associated with Onpattro were upper respiratory tract infections and infusion-related reactions, such as back pain, nausea, flushing, difficulty breathing, and headache. According to Alnylam, patients received premedications prior to Onpattro treatment to reduce the risk of infusion-related reactions.
“It’s extremely gratifying to see promising science translate into a treatment option that will allow patients to potentially experience an improvement in their disease and an improvement in their overall quality of life,” Muriel Finkel, president of Amyloidosis Support Groups, said.
“With an FDA-approved treatment now available, I am more optimistic than ever that we can increase awareness of this rare disease and encourage more people to get tested and receive the proper diagnosis,” added Isabelle Lousada, founder and CEO of the Amyloidosis Research Consortium.
Alnylam is expecting a final decision by September from the European Commission regarding the marketing authorization of Onpattro in all 28 European Union members, Iceland, Liechtenstein, and Norway. The company plans to file for regulatory approval of Onpattro in other markets, including Japan.