Akcea Therapeutics, a wholly-owned subsidiary of Isis Pharmaceuticals, Inc., announced that the US Food and Drug Administration has granted Orphan Drug Designation to volanesorsen (ISIS-APOCIIIRx) for the treatment of patients with Familial Chylomicronemia Syndrome (FCS).  FCS is a rare genetic disease characterized by extremely high triglyceride levels and risk of pancreatitis. In a phase 2 study published in the NEJM in December 2014, patients with FCS treated with volanesorsen achieved substantial reductions in apoC-III, triglycerides, chylomicrons and apoC-III-associated very low density lipoprotein-cholesterol (VLDL-C) particles.  Akcea is currently conducting an international multi-center, randomized, double-blind, placebo-controlled phase 3 study in patients with FCS.  

"FCS is a rare and very serious genetic disorder associated with very high triglyceride levels that put patients at risk of potentially life-threatening pancreatitis.  People with FCS cope with daily consequences of their disease, including persistent abdominal pain and life-altering food restrictions. Unfortunately, current treatment options do not reduce triglyceride levels enough to reduce the risk of serious illness in patients with FCS," said Paula Soteropoulos, president and chief executive officer at Akcea Therapeutics.  "Orphan drug designation for FCS underscores the need for improved therapies to treat patients with FCS and is an important benchmark as we complete the ongoing phase 3 study in patients with FCS and prepare for commercialization."

The Orphan Drug Act provides for economic incentives to encourage the development of drugs for diseases affecting fewer than 200,000 people in the United States.  Orphan drug designation entitles Akcea Therapeutics to seven years of market exclusivity in the United States if market approval is granted for volanesorsen for the treatment of patients with FCS.  Additional incentives include tax credits related to clinical trial expenses, an exemption from the FDA-user fee, and FDA assistance in clinical trial design.

FCS is a rare genetic disorder characterized by extremely high levels of triglycerides that affects an estimated one to two out of a million people.  FCS may also be called familial chylomicronemia, Frederickson Type I hyperlipoproteinemia, familial lipoprotein lipase deficiency (LPLD), or familial hypertryglyceridemia. Some people with FCS may live with recurrent stomach pain, and a high risk or prior history of hospitalization for pancreatitis.  FCS is primarily caused by mutations in genes that produce proteins involved in the clearance of particles that carry triglycerides, called chylomicrons.  Patients with FCS are unable to effectively clear chylomicrons, and as such, have high levels of triglycerides, which increase their risk of pancreatitis, type 2 diabetes and other serious illnesses.

Volanesorsen (ISIS-APOCIIIRx) is an antisense drug in development intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents.  Volanesorsen is designed to target apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides.  Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. Humans with elevated levels of apoC-III have high triglycerides associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome.  In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.  Humans with severely elevated levels of triglycerides are at risk of many serious health conditions, including pancreatitis, which can be life-threatening and require hospitalization.  Volanesorsen is currently being evaluated in a phase 3 study in patients with FCS.  A second phase 3 study of volanesorsen is planned to begin later this year in patients with Familial Partial Lipodystrophy, another severe and rare lipid disorder.  

Akcea Therapeutics is a development and commercialization company focused on transforming the lives of patients with serious cardiometabolic lipid disorders.