Acasti Announces Definitive Agreement to Acquire Grace Therapeutics, Inc.

TRILOGY Phase 3

Trilogy1


TRILOGY, an acronym derived from “Phase 3 Studies of CaPre in Lowering Very High Triglycerides,” was a double-blind, placebo-controlled, 26-week, two-trial Phase 3 clinical program designed to evaluate the safety and efficacy of CaPre in patients with severe hypertriglyceridemia. TRILOGY 1 and TRILOGY 2 ran in parallel and randomized a total of approximately 500 patients. The program was conducted at approximately 150 sites across the U.S., Canada and Mexico.

The primary endpoint of the identical trials was to determine the efficacy of CaPre 4 grams daily compared to placebo in lowering TG levels after 12 weeks of treatment, in subjects with fasting triglyceride levels between 500 mg/dL and 1500 mg/dL. The persistence of the effect of CaPre on TGs over 26 weeks of treatment was also evaluated. Numerous secondary endpoints will assess the effect of CaPre on patients’ broader lipid profile and certain exploratory metabolic, glycemic diabetic markers, inflammatory and cardiovascular risk markers. Safety was also evaluated.

The study was designed to provide at least 90% power to detect a difference of at least a 20% decrease from baseline in triglycerides between CaPre and placebo.

PHASE 3 STUDIES

Acasti conducted two Phase 3 clinical trials: the TRILOGY trials. In TRILOGY 1, CaPre® achieved a 30.5% reduction in triglyceride levels at 12 weeks and 36.7% reduction in triglyceride levels at 26 weeks, as well as 42.2% reduction in triglyceride levels among patients receiving CaPre while on background statin therapy at 12 weeks. Despite positive results in the CaPre arm, the TRILOGY 1 study did not reach statistical significance. In TRILOGY 2, CaPre achieved 30.4% median reduction in triglycerides at 12 weeks and 38.4% at 26 weeks, but did not achieve statistical significance for the primary endpoint.

TRILOGY 1:

The Company reported a 30.5% median reduction in triglyceride levels among all patients receiving CaPre, compared to a 27.5% median reduction in triglyceride levels among patients receiving placebo at 12 weeks. The Company also reported a 42.2% median reduction in triglycerides among patients receiving CaPre while on background statin therapy at 12 weeks, compared to a 31.5% median reduction in triglyceride levels among patients receiving placebo and on background statin therapy. In addition, the Company reported a 36.7% median reduction in triglyceride levels among patients receiving CaPre at 26 weeks (end of the study), compared to a 28.0% median reduction in triglyceride levels among patients receiving placebo. Both the placebo and CaPre study groups experienced significant reductions in triglycerides within the first four weeks from baseline, and even though the difference at 12 and 26 weeks was in favor of CaPre, due to the unexpectedly large placebo response, TRILOGY 1 did not reach statistical significance. The safety profile of CaPre in TRILOGY 1 was similar to placebo, as there were no significant difference in treatment-related serious adverse events in the trial. The observed reductions in triglyceride levels in the placebo group were far greater than that seen in any previous triglyceride lowering trial with a prescription omega-3. The placebo used in the TRILOGY trials is simple cornstarch, which is a complex carbohydrate with a low glycemic index, and consequently would be expected to have a neutral effect on key biomarkers of patients in the placebo group. In similar previously conducted triglyceride lowering trials involving prescription omega-3 preparations, the placebo responses (using corn oil, olive oil, or vegetable oil) ranged from a change of +16% to -17% across 18 interventions arms, with 14 of 18 arms ranging between +10% to -10%.

Trilogy2


TRILOGY 2:

The Company reported a 30.4% median reduction in triglyceride levels among all patients receiving CaPre, as compared to 30.5% in TRILOGY 1, and a 17.9% median reduction in triglyceride levels among patients receiving placebo at 12 weeks (the Primary Endpoint), as compared to 27.5% in TRILOGY 1. The unadjusted, placebo corrected triglyceride reduction of 12.4% achieved a “p” value of 0.19, which was not statistically significant, and therefore the TRILOGY 2 study did not meet its primary endpoint. CaPre was well tolerated in TRILOGY 2, with a safety profile similar to placebo, and consistent with the Company’s previously conducted Phase 2 and 3 studies.

As a result, the company will not file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for patients with severe hypertriglyceridemia, and does not plan to conduct additional clinical trials for CaPre.

Additional information on the TRILOGY program can be found at www.clinicaltrials.gov, with the NCT Identifiers #03398005 and #03361501.