The European Commission (EC) has approved Tegsedi (inotersen), by Akcea Therapeutics and Ionis Pharmaceuticals, to treat stage 1 or 2 polyneuropathy in adults with hereditary transthyretin amyloidosis (hATTR).
The approval — in the form of marketing authorization — comes on the heels of a positive recommendation by the Committee for Medicinal Products for Human Use (CHMP) of European Medicines Agency (EMA). CHMP is responsible for preparing EMA opinions on all questions concerning human medicines.
hATTR amyloidosis is caused by a buildup of misfolded aggregates of a protein called transthyretin (TTR; caused by mutations to the TRR gene) in multiple organs; the protein carries vitamin A and thyroxine (a hormone) about the body. Tegsedi is an RNA-targeted medicine that inhibits the production of the TTR protein. This disease is also known as familial amyloid polyneuropathy (FAP).
“Today, we are thrilled to see our successful research and development efforts result in the approval of an important new medicine for patients with hATTR amyloidosis. Using our antisense technology platform, we set out to design a therapy to block the production of the underlying cause of this disease, the TTR protein,” Brett P. Monia, PhD, chief operating officer at Ionis Pharmaceuticals, said in a press release.
Approval was based on positive results from the Phase 3 NEURO-TTR study (NCT01737398) that evaluated the use of Tegsedi in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. Treatment, weekly subcutaneous injections of 300 mg of Tegsedi for up to 15 months, was found to significantly ease neuropathy symptoms and improve quality of life for a substantial portion of patients.
Treatment with Tegsedi was also associated with a significant decrease in levels of the TTR protein across mutation types or disease stages.
Ionis has also applied to the U.S. Food and Drug Administration (FDA), requesting approval of Tegsedi to treat FAP. A decision is expected later this year.
An expanded access program (NCT03400098), offered by Ionis, is currently enrolling eligible hATTR patients with limited or no available treatment options at 26 sites across the U.S. More information is available here.
Tegsedi is also under regulatory review in Canada.
“TEGSEDI has demonstrated rapid and sustained benefits in improving the course of this disease and preserving quality of life,” said Teresa Coelho, a neurologist at Santo António Hospital, Porto, Portugal.
Ionis granted Akcea, an affiliated company, licensing rights worldwide to commercialize Tegsedi in April. As part of the deal, Akcea will give Ionis a $40 million milestone payment based on EC authorization of Tegsedi. Additionally, profits and losses from Tegsedi will be split 60% to Ionis and 40% to Akcea.