A betting man may have placed a pretty strong wager on the U.S. Food and Drug Administration’s approval of Akcea Therapeutics’ Waylivra (volanesorsen), a treatment for the rare lipid disorder familial chylomicronemia syndrome (FCS).
A betting man may have placed a pretty strong wager on the U.S. Food and Drug Administration (FDA)‘s approval of Akcea Therapeutics’ Waylivra (volanesorsen), a treatment for the rare lipid disorder familial chylomicronemia syndrome (FCS).
In May an FDA advisory committee gave Waylivra the green light, which typically sets the stage for approval. The committee supported approving the drug in a vote of 12-8. But on Monday, the FDA issued a Complete Response Letter to Akcea, a subsidiary of Ionis Pharmaceuticals, which means that a betting man would have lost.
Shares of Akcea have plunged more than 28 percent in premarket trading as the news has spread and investors were stunned by the CRL. The FDA typically follows the recommendation of its advisory committees, although they are clearly not bound to it, which makes this rejection a bit unusual. What makes it even more unusual, and potentially troubling for Akcea and its investors is the company only announced the FDA’s CRL and did not publicly disclose any reason why the drug was rejected.
Paula Soteropoulos, chief executive officer of Akcea Therapeutics, announced the company’s frustration with the FDA’s decision late Monday.
“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,” Soteropoulos said in a statement.
The CRL may have to do with the safety profile of Waylivra. When the drug passed out of the advisory committee, the eight dissenting votes raised concerns over the medication’s safety profile. The primary concern was that the therapy caused dangerous drops in platelet counts in some patients. When Akcea announced Phase III results, the company noted that five patients were forced to withdraw from the trial due to a drop in platelets.
The Phase III trial demonstrated that Waylivra reduced triglycerides by 77 percent in FCL patients. In announcing the CRL, Akcea pointed to clinical practice guidelines supported by the Endocrine Society that recommends triglyceride reduction as the goal of treatment for FCS. Waylivra 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, according to information provided by Akcea.
FCS is a rare disorder where patients have extremely high levels of triglycerides in their blood. That high level causes a range of symptoms including potentially fatal attacks of acute pancreatitis. With limited LPL function, people with FCS cannot breakdown chylomicrons, lipoprotein particles that are 90 percent triglycerides. 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 cognition that affect their ability to work.
Following the FDA advisory committee vote, Brett P. Monia, chief operating officer at Ionis, said Waylivra is the first drug to demonstrate substantial triglyceride lowering in clinical trials in people with FCS. On Monday Monia continued to voice his support for the drug.
“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,” Monia said in a statement.
