Clinical Trials

Date: 2017-03-06

Type of information: Results

phase: 3

Announcement: results

Company: Ionis Pharmaceuticals (USA - CA) Akcea Therapeutics (USA - MA)

Product: volanesorsen (ISIS-APOCIII Rx)

Action mechanism:

• antisense oligonucleotide. IONIS-APOCIIIRx is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents. ISIS-APOCIIIRx targets apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. Humans with elevated levels of apoC-III have high triglycerides associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome.

Disease: familial chylomicronemia syndrome

Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases

Country: Brazil, Canada, France, Germany, Hungary, Israel, Italy, The Netherlands, Spain, UK, USA

Trial details:

• The Phase 3 study (APPROACH study) of IONIS-APOCIIIRx is a randomized, double-blind, placebo-controlled, six month study in approximately 50 patients diagnosed with FCS. The study will evaluate the efficacy and safety of a 300 mg once weekly dose of IONIS-APOCIIIRx. The primary endpoint of the study is percent change in fasting triglycerides from baseline after three months of dosing. (NCT02211209)
• The volanesorsen clinical program is focused on generating data to support registration in two severe, rare, genetic diseases, familial chylomicronemia syndrome and familial partial lipodystrophy. The program is supported by Phase 1 and Phase 2 studies that explored volanesorsen doses across both healthy volunteers and a number of patient populations, including patients with hypertriglyceridemia, Type 2 diabetes, and familial chylomicronemia syndrome. Ttwo Phase 3 studies, APPROACH and COMPASS,  have been completed and support planned regulatory filings for the treatment of familial chylomicronemia syndrome. Patients with familial chylomicronemia syndrome who have completed or meet the study criteria for the APPROACH study can enroll in an open-label extension study. Akcea and Ionis are also currently conducting, BROADEN, a Phase 3 study in patients with familial partial lipodystrophy.

Latest news:

• • On March 6, 2017, Akcea Therapeutics, a wholly owned subsidiary of Ionis Pharmaceuticals, announced that the pivotal Phase 3 APPROACH study of volanesorsen met its primary endpoint of reducing triglyceride levels in patients with familial chylomicronemia syndrome. APPROACH involved 66 patients with familial chylomicronemia syndrome. 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:
• - volanesorsen-treated patients (n=33) achieved a statistically significant 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.
• Volanesorsen-treated patients with the highest documented frequency of pancreatitis attacks suffered no attacks during the 52-week treatment period.
• A reduction in abdominal pain was observed in volanesorsen-treated patients compared to placebo-treated patients.
• The APPROACH study will support the regulatory submission for familial chylomicronemia syndrome of volanesorsen. Additional data from the study will be presented at an upcoming medical meeting.
• 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 familial chylomicronemia syndrome 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.
• • On August 28, 2014, Isis Pharmaceuticals announced the initiation of a Phase 3 study evaluating IONIS-APOCIIIRx in patients with familial chylomicronemia syndrome (FCS). FCS is a rare orphan disease, characterized by extremely high triglyceride levels, that affects an estimated 3,000 to 5,000 patients worldwide. In a Phase 2 study, FCS patients treated with ISIS-APOCIIIRx experienced decreases in triglycerides of up to more than 1,500 mg/dL. Isis has also evaluated ISIS-APOCIIIRx in a broad Phase 2 program. In these studies in patients with very high to extremely high triglyceride levels, patients treated with ISIS-APOCIIIRx achieved substantial lowering of triglycerides (mean percent reductions of up to 71%) and apoC-III (mean percent reductions of up to 88%) and increasing of HDL-cholesterol (mean percent increases of up to 78%).

Is general: Yes