Akcea Therapeutics, Inc. an affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc., received a Complete Response Letter (CRL) from the Division of Metabolism and Endocrinology Products of the U.S. Food and Drug Administration (FDA) regarding the New Drug Application (NDA) for Waylivra (volanesorsen).
“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. We continue to feel strongly that Waylivra demonstrates a favorable benefit/risk profile in people with FCS as was reflected in the positive outcome from our Advisory Committee hearing in May. We will continue to work with the FDA to confirm the path forward,” said Paula Soteropoulos, chief executive officer of Akcea Therapeutics.
Familial chylomicronemia syndrome (FCS) is an ultra-rare, devastating hereditary disease that causes unpredictable and potentially fatal acute pancreatitis, chronic complications due to permanent organ damage, and a severe impact on daily living. The hallmark of FCS is extremely elevated triglycerides.
Results from the Phase 3 Approach trial, the largest study ever conducted in patients with FCS, show that in comparison to placebo, treatment with Waylivra reduced triglycerides by 77 percent (-94 percent when compared to placebo). The Endocrine Society and current clinical practice guidelines recommend triglyceride reduction as the goal of treatment for FCS. The most common adverse events in the Approach study were injection site reactions and reductions in platelet levels.
“We are fully supportive of Waylivra and the many patients, physicians and researchers who are working to provide the first therapeutic option for FCS, a truly life-altering disease that deserves a treatment,” said Brett P. Monia, Ph.D., chief operating officer of Ionis Pharmaceuticals.
About Watlivra and FCS
Waylivra, a product of Ionis’ proprietary antisense technology, 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 and may also affect other metabolic parameters.
Waylivra is also under regulatory review in the E.U. and Canada for the treatment of people with familial chylomicronemia syndrome (FCS).
FCS is an ultra-rare disease caused by impaired function of the enzyme lipoprotein lipase (LPL) and characterized by severe hypertriglyceridemia, or triglyceride levels that can be greater than 10 times normal values, and the risk of unpredictable and potentially fatal acute pancreatitis. Because of limited LPL function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90 percent triglycerides.
In addition to pancreatitis, people with FCS are at risk of chronic complications due to permanent organ damage, including chronic pancreatitis and pancreatogenic diabetes. They can experience daily symptoms including abdominal pain, generalized fatigue and impaired cognition that affect their ability to work. People with FCS also experience major emotional and psychosocial effects including anxiety, social withdrawal, depression and brain fog. There is no effective therapy for FCS currently available. Additional information on FCS is available at www.fcsfocus.com, and through the FCS Foundation at http://www.livingwithfcs.org and the LPLD Alliance at www.lpldalliance.org.
Waylivra is also currently in Phase 3 clinical development for the treatment of patients with familial partial lipodystrophy, or FPL. Akcea anticipates reporting top-line data from this study in 2019.
(Source: Akcea Therapeutics, Inc.)