The FDA approved inotersen (Tegsedi) to treat polyneuropathy associated with hereditary transthyretin (hATTR) amyloidosis, Friday.
But the approval came with a boxed warning and mandatory laboratory monitoring for possibly life-threatening thrombocytopenia and glomerulonephritis. And because of these risks, inotersen will be available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS).
Formerly called familial amyloid polyneuropathy, hATTR amyloidosis is a rare, rapidly progressive disease caused by a mutation in the TTR gene that results in the buildup of misfolded transthyretin and leads to amyloid deposits in the heart, gastrointestinal tract, and peripheral nerves. Life expectancy is about 3 to 15 years after the onset of neuropathy.
In the phase III NEURO-TTR trial, inotersen, an antisense oligonucleotide inhibitor of transthyretin protein production, bettered the neurologic disease course and quality of life in patients with stage 1 or stage 2 hATTR amyloidosis, producing up to a 79% mean decrease from baseline in serum TTR protein. The drug's most common side effects were injection site reactions, nausea, headache, fatigue, thrombocytopenia, and fever.
Inotersen is the first RNA-targeting drug that reduces the production of TTR protein through a once-weekly subcutaneous injection, noted Akcea CEO Paula Soteropoulos. Self-administration will give patients "the flexibility to treat at a time that works for them, which could change the way this progressive and debilitating disease is treated and managed," she said in a statement.
Inotersen is the second drug for hATTR amyloidosis nerve pain to win FDA approval, following patisiran (Onpattro), an RNA interference (RNAi) drug that requires an every 3 weeks.
On Thursday, an (ICER) final evidence report concluded neither drug could meet the threshold for long-term cost effectiveness unless patisiran was priced below $200,000 and inotersen below $96,103 a year.
Inotersen will have a "maximum annual price of $450,000," Soteropoulos stated in a conference call Friday after the FDA approval announcement. Making inotersen widely available to patients is the next step: "We're now in launch mode," she said. To that end, Akcea will , a subsidiary of Express Scripts, to distribute the drug.
The inotersen label will contain warnings about stroke and cervical artery dissection, inflammatory and immune problems, liver effects, hypersensitivity reactions, a potential interaction that can lead to platelet counts that cannot be interpreted, and eye problems stemming from reduced levels of vitamin A.
In April, Akcea licensed the rights to commercialize inotersen from Ionis. The drug was on Thursday and earlier this year.