WASHINGTON -- The FDA said Friday it had , caused by a gene mutation that leads to amyloid deposits in nerves and tissues.
Not only is patisiran the first drug with this indication, it's also the first so-called RNA interference (RNAi) agent to win approval for any condition, the FDA noted.
Formerly known as familial amyloid polyneuropathy, hATTR amyloidosis is a rapidly progressive disease caused by a mutation in the TTR gene that results in the buildup of misfolded transthyretin protein, leading to amyloid deposits in the heart, gastrointestinal tract, and peripheral nerves. Life expectancy of patients is about 3 to 15 years after the onset of neuropathy, less in patients who have cardiomyopathy.
In the phase III APOLLO trial, patisiran slowed peripheral neuropathy progression in patients with hATTR amyloidosis, improving neurological impairment and clinical manifestations by over 18 months.
In that trial, involving 225 patients, those "who received Onpattro had better outcomes on measures of polyneuropathy including muscle strength, sensation (pain, temperature, numbness), reflexes and autonomic symptoms (blood pressure, heart rate, digestion) compared to those receiving the placebo infusions," the FDA noted in its approval announcement. "Onpattro-treated patients also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living."
Adverse effects seen in the clinical studies included infusion-related reactions, back pain, nausea, abdominal pain, dyspnea, and headache, the FDA said. All patients in the trials were pretreated with acetaminophen, antihistamines, and a corticosteroid to minimize infusion reactions. Visual effects were also noted, including dry eye, blurred vision, and "floaters."
Because patisiran can diminish vitamin A levels in serum, patients should take an oral supplement providing the recommended daily allowance.
Patisiran, manufactured by Alnylam Pharmaceuticals, recently received a from Europe's main drug review committee for hATTR amyloidosis in adults with stage 1 or stage 2 polyneuropathy, and the United Kingdom's Medicines and Healthcare Products Regulatory Agency decided last week to make it before it receives formal marketing authorization.
RNAi technology -- also called siRNA for small interfering RNA -- uses short nucleic acid strings to interrupt gene translation and expression. Two U.S. geneticists who won a in 2006, and drug developers have been seeking to exploit it for therapeutic purposes for longer than that.
Contributing writer Judy George provided background material for this report.