Akcea Therapeutics, and Ionis Pharmaceuticals have announced that a marketing authorization application (MAA) has been submitted to the European Medicines Agency (EMA) for volanesorsen for the treatment of patients with familial chylomicronemia syndrome (FCS).
Volanesorsen, a product of Ionis' proprietary antisense technology, was discovered by Ionis and co-developed by Ionis and Akcea and, if approved, will be commercialized by Akcea.
"The submission of the volanesorsen MAA to the EMA represents a critical milestone for Akcea. This filing brings us one step closer to our goal of providing physicians and patients with a treatment for a disease with multiple, severe, daily and chronic manifestations," said Paula Soteropoulos, president and chief executive officer of Akcea. "We have had productive communications with regulatory agencies in the EU, the U.S., and Canada, and are on track to also complete regulatory submissions in the U.S. and Canada in September. Further, Akcea is building the organization and infrastructure to commercialize volanesorsen globally."
FCS is a severe, rare disorder characterized by extremely high levels of triglycerides and the risk of recurrent, potentially fatal pancreatitis. People with FCS are unable to effectively metabolize large, triglyceride-rich lipid particles called chylomicrons due to a deficiency in lipoprotein lipase, an enzyme that helps to break down triglycerides. There is no effective therapy available.
"Patients with FCS need new therapies that can meaningfully lower their severely elevated triglycerides. Because of their very high triglycerides, these patients suffer from daily and chronic symptoms and are at significantly increased risk for morbidity and mortality, primarily due to recurrent attacks of pancreatitis," said Dr. Marcello Arca, Head of the Lipid and Atherosclerosis Unit of the University Hospital Policlinico Umberto I. "Based on the positive results from the Phase 3 program with volanesorsen, I'm encouraged that for the first time, these patients may have a new therapy that can help them achieve the triglyceride reductions they need to lessen the burden of their disease and decrease their risk for pancreatitis."
"Akcea has shown great commitment in supporting patients and working to find a treatment for this debilitating condition. Their work means that the European FCS community of patients, families, and physicians are one step closer to having an effective treatment that will make the life-long struggle of living with the burden of FCS much more manageable. It is great to be working with a supportive partner like Akcea, and we also appreciate the perseverance of our community in the quest to find an effective treatment," said Jill Prawer, Founder and Chair, LPLD Alliance.
The submission of volanesorsen for the treatment of FCS is based on data from the Phase 3 APPROACH and COMPASS studies. The pivotal APPROACH study, a one-year, randomized, placebo-controlled study in 66 patients with FCS (average baseline triglycerides of 2,209 mg/dL, or 25.0 mmol/L), achieved its primary endpoint of reduction in triglycerides at three months, with a 77% mean reduction in triglycerides, which translated into a 1,712 mg/dL (19.3 mmol/L) mean absolute triglyceride reduction in volanesorsen-treated patients. This compared to an 18% increase for placebo, or a -94% treatment effect. Further, 50% of treated patients achieved triglyceride levels below 500 mg/dL (5.6 mmol/L), a recognized threshold for enhanced pancreatitis risk. In addition, in the APPROACH study, treatment with volanesorsen was associated with a statistically significant reduced rate of on-study pancreatitis attacks in the group of patients who had a higher incidence of pre-study pancreatitis and reduced abdominal pain in patients reporting pain as a prominent pre-treatment symptom.
The COMPASS study, a six-month randomized placebo-controlled study in 113 patients with very high triglycerides (>500 mg/dL), also achieved its primary endpoint of reduction in triglycerides at three months, with a 71% mean reduction in triglycerides. In the COMPASS study, treatment with volanesorsen was associated with a statistically significant reduction in on-study pancreatitis attacks.
The most common adverse event in the studies was injection site reactions, which were mostly mild. Platelet count reductions were observed in many patients. These platelet declines were not clinically significant in most patients and were generally well managed with monitoring and dose adjustment. Five patients discontinued participation in the APPROACH study due to platelet count reductions, two of which were severe; four patients discontinued due to other nonserious adverse events.
Akcea and Ionis continue to conduct the BROADEN study, a Phase 3 clinical trial in patients with FPL, which continues to enroll, with topline data expected in 2019. Akcea plans to file for marketing authorization for volanesorsen to treat FPL in 2019 if the data from the BROADEN study are positive. The U.S. and EU regulatory agencies have granted Orphan Drug Designation to volanesorsen for the treatment of patients with FCS. Volanesorsen has also received Orphan Drug Designation in the EU for the treatment of FPL.