The FDA served up a Complete Response Letter for Akcea Therapeutics’ volanesorsen, rejecting the antisense drug for familial chylomicronemia syndrome (FCS), a rare lipid disorder. The denial comes three months after volanesorsen squeaked past an FDA advisory committee, which voted 12-8 to recommend its approval.
"We are extremely disappointed with the FDA's decision. FCS is an ultra-rare and debilitating disease. Our disappointment extends to the patient and physician community who currently do not have a treatment available to them,” said Akcea CEO Paula Soteropoulos in a statement on Monday.
“We will continue to work with the FDA to confirm the path forward," Soteropoulos said. But the company did not specify in its statement why the agency rejected the drug, nor did it say how it planned to move forward with the submission. Akcea’s stock dipped 24% in afterhours trading.
Volanesorsen, also known as Waylivra, was one of four programs that Ionis Pharma offloaded when it spun out Akcea in 2015. It is designed to treat FCS, which has no FDA-approved therapies. The disorder is caused by a genetic mutation that causes deficient triglyceride processing and, in some patients, leads to potentially life-threatening pancreatitis. While it typically appears in childhood or adolescence, the condition tends to be diagnosed late because it is so rare.
An antisense oligonucleotide, volanesorsen works by inhibiting apolipoprotein C-III (ApoC-III), protein made in the liver that regulates triglyceride metabolism. Akcea is seeking approval for volanesorsen as an adjunct to diet, the go-to treatment for patients with FCS.
FDA staff flagged several concerns in their briefing documents, namely the risk of serious bleeding and thrombocytopenia—low blood platelet count—associated with volanesorsen, whether the drug needs a risk evaluation and mitigation strategy, and if FCS is a specific enough description of the target population for the drug’s approval.
And, as if that wasn’t enough, Akcea unexpectedly submitted an amendment to its NDA submission proposing a new dosing and platelet monitoring strategy that had not been tested in clinical trials.
Had it been approved, volanesorsen would have been Akcea’s first marketed drug in the U.S. It sells another antisense drug, inotersen, as Tegsedi in the European Union. Akcea became the commercialization partner for the Ionis-developed drug after GlaxoSmithKline, Ionis’ original partner, ditched the deal in August last year.
Editor's note: This article has been updated with the correct year Akcea was formed. It was spun out in 2015, not 2017 as previously stated. Akcea filed for its IPO in March 2017.