EU’s CHMP Recommends Approval of Tegsedi (Inotersen) for Treatment of FAP

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tegsedi (inotersen) as a treatment for Stage 1 or 2 polyneuropathy in adults with hereditary transthyretin amyloidosis (hATTR), also known as familial amyloid polyneuropathy (FAP).

The announcement comes from Akcea Therapeutics and Ionis Pharmaceuticals. Akcea, an affiliate of Ionis, acquired the TTR program in March.

CHMP’s opinion will now be considered by the European Commission, which is responsible for granting marketing authorization for medications in the European Union and for European Economic Area members, including Iceland, Liechtenstein, and Norway.

“Today’s positive CHMP opinion is an important step toward making TEGSEDI available to people with this systemic, progressive and fatal hereditary disease that relentlessly deprives them of their independence and dignity,” Paula Soteropoulos, CEO of Akcea Therapeutics, said in a press release.

“We are now anticipating approval in Europe shortly and we are ready to launch TEGSEDI to bring this new treatment to people with hATTR amyloidosis [FAP],” she added.

CHMP’s recommendation to approve Tegsedi is based on encouraging results from Ionis’ Phase 3 NEURO-TTR study (NCT01737398) and the open-label extension study (NCT02175004), which demonstrated that Tegsedi showed significant benefit in patients with FAP compared to patients treated with placebo.

Tegsedi was found to be effective in both primary endpoints: the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and the modified Neuropathy Impairment Score +7 (mNIS+7), which measures  disease progression.

Additionally, treatment with Tegsedi led to a significant reduction in levels of the transthyretin (TTR) protein, the accumulation of which is the underlying cause of FAP.

“The benefit demonstrated by TEGSEDI in the Phase 3 NEURO-TTR trial on both measures of quality of life and neurological disease progression provides hope for patients and their families that they may be able to maintain greater independence from their disease by alleviating debilitating symptoms while preserving their ability to perform daily activities,” said Teresa Coelho, MD, neurologist and neurophysiologist at Santo António Hospital in Porto, Portugal.

The adverse effects of Tegsedi treatment includes risk of thrombocytopenia (low platelet levels) and glomerulonephritis (kidney inflammation), which were effectively managed by enhanced monitoring and early detection and management.

Tegsedi is an antisense drug that is targeted to reduce the production of the TTR protein. Antisense drugs interact with and inactivate mRNA, the molecule that leads to the production of a protein.

“This positive CHMP opinion moves Ionis one step closer to becoming a multi-product sustainably profitable company delivering life-changing drugs to patients,” said Brett P. Monia, PhD, chief operating officer at Ionis Pharmaceuticals.

“Our antisense technology platform continues to deliver many important scientific and medical advances that should support continuing growth,” he said. “We remain highly committed to bringing TEGSEDI and other drugs from our pipeline to patients.”

Tegsedi is also under regulatory review for marketing approval in the United States and Canada. It has been granted orphan drug and fast track status by the U.S. Food and Drug Administration and the EMA.