Akcea Therapeutics has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for volanesorsen to treat patients with familial chylomicronemia syndrome (FCS).
FCS is a rare genetic disease characterized by the build up of chylomicrons (chylomicronemia), large lipoprotein particles that are responsible for transporting dietary fat and cholesterol. Typically, the enzyme lipoprotein lipase (LPL) breaks down chylomicrons in the blood.However, in people with FCS, LPL does not function properly leading to higher triglyceride levels. Normal triglyceride levels are <150 mg/dL (or 1.7 mmol/L) but people with FCS often have triglyceride levels 10 times higher than normal. Currently, there is not effective treatment for this condition and patients must maintain a very strict, low-fat diet.
In a news release, Paula Soteropoulos, president and chief executive officer of Akcea said, “We have successfully submitted marketing authorization applications in the U.S., the E.U. and we are on track to submit our application for marketing authorization in Canada in September. We are also on track to launch volanesorsen globally in 2018 pending approval in the respective markets.”
“Because of drastically impaired function of lipoprotein lipase, patients with FCS have triglyceride levels that can reach 10 to 20 times that of healthy individuals. This frequently leads to recurrent episodes of acute pancreatitis, which can be fatal. Today, there is no therapy for FCS patients that can effectively reduce their triglycerides to levels that are even close to acceptable,” said Dr. Linda C. Hemphill of Massachusetts General Hospital and Harvard Medical School. “I am encouraged that the significant reductions in triglyceride levels and reduced risk of pancreatitis in the APPROACH and COMPASS studies indicate that we may soon have an option for these patients."
The NDA includes data from two Phase 3 clinical trials – the APPROACH and COMPASS studies.
The pivotal APPROACH study was a 1-year, randomized, placebo-controlled study in which 66 patients with FCS received valonesorsen or placebo and the study achieved its primary endpoint with a 77% reduction in triglycerides after 3 months of volanesorsen treatment compared to a 13% increase in the placebo treated group.
The COMPASS study was a 6-month randomized placebo-controlled study in 113 patients with very high triglycerides (>500 mg/dL). It also achieved its primary endpoint with a 71% reduction in triglycerides after 3 months of volanesorsen treatment.
The most common adverse event in the studies was injection site reactions, which were mostly mild.
The company noted that platelet count reductions were observed in many patients and 5 Five discontinued participation in the APPROACH study due to platelet count reductions.
Richard Dunbar, MD of the Perelman School of Medicine at the University of Pennsylvania talks about what patients, caregivers and physicians should understand about FCS.
Volanesorsen is an antisense drug in development for 2 rare metabolic disorders: FCS and familial partial lipodystrophy (FPL). Volanesorsen is designed to reduce the production of ApoC-III, a protein produced in the liver that plays a central role in the regulation of plasma triglycerides.
In 2015, we talked with Paula Soteropoulos of Akcea about volanesorsen (also known as ISIS-APOCCIII Rx). That interview is below.