FDA Rejects Volanesorsen (Waylivra) for Rare Triglyceride Disorder

Megan Brooks

Disclosures

September 04, 2018

The US Food and Drug Administration (FDA) has rejected the new drug application for volanesorsen (Waylivra, Akcea/Ionis) for the ultrarare lipid disorder familial chylomicronemia syndrome (FCS), the companies have announced.

In a news release, the companies said they received a complete response letter  from the FDA but did not divulge the reasons for the rejection or the concerns the FDA had.

"We are extremely disappointed with the FDA's decision," Paula Soteropoulos, chief executive officer of Akcea Therapeutics, said in the release.

"FCS is a devastating and potentially fatal disease, and patients currently have no treatment options available. We feel strongly that the clinical data demonstrate that Waylivra offers a positive benefit/risk profile in the treatment of FCS," Soteropoulos told Medscape Medical News.

"We are working through the feedback and intend to meet with FDA as it is critical that we find a way to approve this much needed therapy," said Soteropoulos.

The rejection is somewhat of a surprise given that the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted (12 to 8) in favor of approving volanesorsen back in May.  

FCS, characterized by extremely high triglyceride levels, affects 3000 to 5000 people worldwide. Volanesorsen is an antisense drug designed to reduce triglyceride levels by reducing production of the liver protein apolipoprotein C-III.

As previously reported by Medscape Medical News, in the phase 3 APPROACH trial, patients treated with volanesorsen experienced mean triglyceride reductions of 77% from baseline after 3 months of treatment (P < .0001), with a mean absolute reduction of 1712 mg/dL. That compares with a mean increase of 18% in patients receiving placebo. The average triglyceride level of those in the study was 2209 mg/dL.

The treatment effect persisted over a 52-week treatment period.

About half the volanesorsen-treated patients who had triglyceride levels of 750 mg/dL or greater had triglyceride levels less than 500 mg/dL after 3 months of treatment (P < .003), while none of the placebo patients experienced the same level of decrease.

The most common adverse events in the 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 Monia, PhD, chief operating officer of Ionis Pharmaceuticals, said in the release.

Volanesorsen for FCS is under regulatory review in the European Union and Canada. The drug is also in phase 3 clinical development for the treatment of patients with familial partial lipodystrophy, with top-line results expected in 2019.

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