Akcea Therapeutics, a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), today announced that the pivotal Phase 3 APPROACH study of volanesorsen met its primary endpoint of reducing triglyceride levels in patients with familial chylomicronemia syndrome (FCS).

APPROACH is a randomized, double-blind, placebo-controlled, 52-week Phase 3 study in 66 patients with FCS, a rare disease affecting approximately 3,000 to 5,000 patients worldwide. The average incoming triglyceride level of patients in the study was 2,209 mg/dL.  Patients treated with volanesorsen experienced robust reductions in triglycerides and related benefits as follows: 

  • For the primary endpoint of the study, volanesorsen-treated patients (n=33) achieved a statistically significant (p<0.0001) mean reduction in triglycerides of 77% from baseline after 3 months of treatment, compared to a mean increase of 18% in placebo-treated patients (n=33).  This represented a mean absolute reduction of 1,712 mg/dL in treated patients.   
  • The treatment effect observed was sustained over the 52-week treatment period. 
  • 50% of the treated patients who entered the study with triglycerides ≥750 mg/dL achieved triglyceride levels less than 500 mg/dL after 3 months of treatment. By comparison, none of the placebo-treated patients achieved this level (p<0.003). 
  • Volanesorsen-treated patients with the highest documented frequency of pancreatitis attacks suffered no attacks during the 52-week treatment period (p=0.02). 
  • A reduction in abdominal pain was observed in volanesorsen-treated patients compared to placebo-treated patients. 

“We are excited about the strong profile of volanesorsen in not only robustly reducing triglycerides, but also providing additional important patient benefits.  FCS is a life-threatening, rare disease with multiple severe daily and chronic manifestations. We believe the efficacy and safety data from volanesorsen studies demonstrate a favorable risk-benefit profile for patients with FCS,” said Paula Soteropoulos, president and chief executive officer, Akcea Therapeutics.  

The APPROACH study will support the regulatory submission for FCS of volanesorsen. Additional data from the study will be presented at an upcoming medical meeting.

“People with FCS have inherited mutations that inhibit the activity of lipoprotein lipase, the enzyme required to break down triglycerides carried by chylomicrons.  The results from this study provide encouraging data about triglyceride reduction in patients with FCS treated with volanesorsen, and are consistent with data from other clinical trials with the drug.  Since there are currently very few effective treatment options for FCS patients, I am encouraged that, if approved, volanesorsen could offer FCS patients an option to achieve the therapeutic benefit they need,” said Daniel Gaudet, M.D. Ph.D., head of the Clinical Lipidology and Rare Lipid Disorders Unit, Community Gene Medicine Center, Department of Medicine, Université de Montreal.

The APPROACH results were consistent with findings from both the Phase 3 COMPASS study as well as the Phase 2 program for volanesorsen.  In the COMPASS study, the five FCS patients treated for three months with volanesorsen experienced a 73% average decrease in triglycerides, which represented a mean absolute reduction of 1,511 mg/dL. In the Phase 2 program, which was the subject of two separate publications in the New England Journal of Medicine, the three FCS patients profiled in one publication had an average triglyceride reduction after three months of treatment with volanesorsen of 69% or a mean absolute reduction of 1,298 mg/dL.  

“The success of APPROACH represents an important milestone towards our first regulatory submissions for volanesorsen in the U.S., Europe and Canada in 2017,” said Dr. Louis O’Dea, chief medical officer, Akcea Therapeutics.  “We seek to bring this new treatment as expeditiously as possible to FCS patients who have a high unmet need with potentially life-threatening consequences.” 

In the study, there were no treatment-related liver adverse events, including no increases in liver fat.  There were no treatment-related renal adverse events.  The most common adverse event in the volanesorsen-treated group of patients was injection site reactions (ISRs), which were mostly mild.  Five volanesorsen-treated patients discontinued due to ISRs.  Declines in platelet counts associated with decreases in triglycerides were observed in many patients. These were generally well managed with dose adjustment.  Five volanesorsen-treated patients discontinued due to declines in platelets. No patients discontinued in the last six months of the study after platelet monitoring was fully implemented.  In the volanesorsen Phase 3 program, there were infrequent serious platelet events (grade 4 thrombocytopenia) in three volanesorsen-treated patients, which resolved without incident following cessation of dosing.  In the entire volanesorsen clinical program 232 individuals have been treated with volanesorsen, including 66 FCS patients, some for more than two years. 

4,721 thoughts on “Akcea Therapeutics’ Volanesorsen Study Meets Primary Endpoint of Reducing Triglyceride Levels in Patients with Familial Chylomicronemia Syndrome (FCS)”

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