An FDA advisory committee voted to recommend the approval of volanesorsen (Waylivra), an RNAi drug for rare lipid disorder familial chylomicronemia syndrome (FCS). The FDA is expected to make it’s final decision by Aug. 30. The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted 12-8 in favor of approval for this treatment for this very rare disorder.
Although the panel vote is not binding, the FDA tends to follow committee recommendations, especially for rare diseases. FCS is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia (>880mg/dL) and a risk of unpredictable and potentially fatal acute pancreatitis. Because of limited LPL function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90% triglycerides. In addition to pancreatitis, FCS patients are at risk of chronic complications due to permanent organ damage. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognitions that affect their ability to work. There are currently no FDA-approved therapies for FCS.
Volanesorsen is an antisense oligonucleotide that inhibits apolipoprotein C-III (ApoC-III), a protein made in the liver that regulates triglyceride metabolism. Akcea is seeking approval for the drug as an adjunct to diet in patients with FCS.
The Advisory Committee reviewed data from two Phase 3 clinical trials, APPROACH and COMPASS, as well as the ongoing APPROACH Open Label study for WAYLIVRA. Results from the phase 3 APPROACH trial, the largest study ever conducted in patients with FCS, show that patients with FCS treated with WAYLIVRA achieved a statistically significant mean reduction in triglycerides of 77% from baseline and decreased risk of pancreatitis. The most common adverse events in the APPROACH study were injection site reactions and platelet declines. The Committee’s input will be considered by the FDA in its review of the New Drug Application for WAYLIVRA. The FDA is not bound by the Committee’s guidance, but takes its advice into consideration when reviewing investigational medicines. WAYLIVRA is also under regulatory review in the European Union and Canada.
“People with FCS have severely elevated triglycerides, which lead to multiple severe daily and chronic symptoms, such as abdominal pain and increased risk for pancreatitis, which can be fatal. WAYLIVRA is the first drug to demonstrate substantial triglyceride lowering in clinical trials in people with FCS,” said Brett P. Monia, chief operating officer at Ionis. “WAYLIVRA illustrates how our antisense technology can create targeted drugs for people living with severe diseases who currently have no available therapeutic options.”
Akcea Therapeutics’ press release announcing this news can be found here.
