The US Food and Drug Administration (FDA) has rejected an antisense drug to treat elevated triglycerides, despite an earlier positive opinion from an advisory panel supporting the approval. The drug Waylivra (volanesorsen), developed by antisense specialist Ionis Pharmaceuticals and its affiliate Akcea Therapeutics, received a Complete Response Letter stating concerns over the drug's risk/benefit profile, including platelet declines seen in clinical studies. Waylivra reduces the production of apolipoprotein C-III, a protein produced in the liver that regulates plasma triglycerides. The sponsors sought approval to treat familial chylomicronemia syndrome, a-rare hereditary disease caused by impaired function of the enzyme lipoprotein lipase and characterized by extremely elevated triglycerides, which can cause unpredictable and potentially acute pancreatitis as well as organ damage.

Analysts are worrying over what the FDA setback could mean for a second Ionis/Akcea antisense drug, Tegsedi (inotersen), which was recently approved in the European Union for treatment of polyneuropathy in adults with hereditary transthyretin amyloidosis (hATTR). Tegsedi is a more important revenue driver for Akcea, and many analysts continue to predict FDA approval of the compound. Madhu Kumar, analyst at B. Riley FBR, takes a different view. The agency's refusal undercuts the argument “that development of a monitoring system will be sufficient to address concerns around platelet losses on phosphorothiate ASO [antisense nucleotide],” he wrote in a note to investors. Tegsedi would compete with Alnylam Pharmaceuticals' Onpattro (patisiran), which gained United States and European approvals in August to treat hATTR. Because Onpattro works through a different mechanism, RNA interference, to block production of transthyretin in the liver, it does not raise the same safety risks as Tegsedi.