FDA approves new treatment for hereditary transthyretin-mediated amyloidosis


The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

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Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 109/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

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