Date: 2016-12-19
Type of information: Results
phase: 3
Announcement: results
Company: Akcea Therapeutics (USA - CA), a subsidiary of Ionis Pharmaceuticals (USA - CA)
Product: volanesorsen (phosphorothioate oligonucleotide targeted to apolipoprotein C-III - IONIS-APOCIIIRx)
Action
mechanism: antisense oligonucleotide. Phosphorothioate oligonucleotide targeted to apolipoprotein C-III (ISIS-APOCIIIRxSIS-APOCIIIRx) is an antisense drug that targets apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides.
Disease: hypertriglyceridemia
Therapeutic area: Metabolic diseases
Country: Canada, France, Germany, Netherlands, UK, USA
Trial
details: The COMPASS Study is a randomized, double-blind, placebo-controlled phase 3 study of ISIS 304801 administered subcutaneously to patients with hypertriglyceridemia. The purpose of this study is to evaluate the efficacy and safety of volanesorsen given for 26 weeks in patients with hypertriglyceridemia. (NCT02300233) The COMPASS study is one of three ongoing global trials that form the Phase 3 program for volanesorsen. It is designed to provide important safety data in support of future regulatory filings in the U.S., E.U. and Canada for volanesorsen in two indications – familial chylomicronemia syndrome (FCS) and familial partial lipodystrophy (FPL). Akcea's two other ongoing international, multi-center Phase 3 studies of volanesorsen are the APPROACH study in patients with FCS and the BROADEN study in patients with FPL.
Latest
news: * On December 19, 2016, Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals, announced that the Phase 3 COMPASS study met its primary endpoint. COMPASS is a randomized, double-blind, placebo-controlled, 26-week Phase 3 study evaluating volanesorsen in 113 patients with severe hypertriglyceridemia. The average incoming triglyceride level of patients in the study was 1,261 mg/dl. Patients treated with volanesorsen experienced clinically meaningful benefits on triglycerides as summarized below: For the primary endpoint of the study, volanesorsen-treated patients (n=75) achieved a statistically significant (p<0.0001) mean reduction in triglycerides of 71.2% from baseline after 13 weeks of treatment, compared with a mean reduction of 0.9% in placebo-treated patients (n=38). This represented a mean absolute reduction of 869 mg/dl in treated patients. The treatment effect observed was sustained through the end of the 26 week treatment period. COMPASS results were consistent with findings from the Phase 2 program for volanesorsen, which were published twice in the New England Journal of Medicine. In the three FCS patients profiled in one publication, the incoming average triglyceride number was 1,844 mg/dl, and the average triglyceride reduction after three months of dosing with volanesorsen was 1,298 mg/dl. In the COMPASS study, the average incoming triglyceride level of the five FCS patients treated with volanesorsen was 2,134 mg/dl, and the average triglyceride reduction was 1,511 mg/dl after three months of dosing. The most common adverse event in the volanesorsen-treated group of patients was injection site reactions (ISRs), which were mostly mild. In this study with patients who are largely asymptomatic and, unlike FCS patients, do not need to manage the daily burden and symptoms of their disease, 13% of treated patients discontinued due to ISRs and 7% of treated patients discontinued treatment for other non-serious adverse events. There were no deaths in the study. None of the FCS patients in the study discontinued. In addition, there were no serious platelet events in the study. There was one potentially related SAE on the drug-treated arm. This was a report of serum sickness that occurred two weeks after the last study dose and resolved without treatment, and after thorough investigation the sponsor determined that the case was not likely caused by the drug. Akcea plans to have top-line data from the pivotal APPROACH study in patients with FCS in the first quarter of 2017. Akcea plans to have data from the pivotal BROADEN study in patients with FPL in 2019. Patients with FCS who have completed or meet the study criteria for the APPROACH and COMPASS studies can enroll in an open-label extension (APPROACH OLE) study. Patients in the BROADEN study are also eligible to roll over into an open-label extension study upon completing dosing in the pivotal study. * On May 16, 2016, Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals focused on developing and commercializing innovative treatments for serious cardiometabolic diseases, announced the completion of enrollment in the COMPASS study, a randomized, double-blind, placebo-controlled, Phase 3 study of volanesorsen in patients with severe hypertriglyceridemia. The APPROACH Phase 3 study in FCS patients completed enrollment at the end of 2015 and data from this study are expected in the first half of 2017. Data from the BROADEN Phase 3 study in FPL are planned for the first half of 2018.
In a subset of seven patients with familial chylomicronemia syndrome (FCS), whose average incoming triglyceride level was 2,280 mg/dl, volanesorsen-treated patients (n=5) achieved a mean reduction in triglycerides of 73% from baseline after 13 weeks of treatment, compared with a mean increase of 70% in placebo-treated patients (n=2). This represented a mean absolute reduction of 1,511 mg/dl in treated patients. The treatment effect observed was sustained through the end of the 26-week treatment period.
In addition, 82% of patients treated with volanesorsen, including three of the FCS patients, achieved triglyceride levels less than 500 mg/dl after 13 weeks of treatment, compared to 14% of placebo-treated patients (p<0.0001).
Ionis and Akcea management plan to discuss the results from this study at an upcoming Ionis pipeline update call on January 5, 2017, and also to present additional data from the study at an upcoming medical meeting.
