LAVAL, Quebec, Feb 14, 2020 (GLOBE NEWSWIRE via COMTEX) -- Acasti Pharma Inc. ("Acasti or the "Company") , a biopharmaceutical innovator focused on the research, development and commercialization of its prescription drug candidate CaPre (omega-3 phospholipid) for the treatment of severe hypertriglyceridemia (HTG) (triglyceride blood levels from 500 mg/dL to 1500 mg/dL), today provided a business update and announced its operating and financial results for the third quarter of fiscal 2020 ended December 31, 2019. All amounts are in Canadian dollars.
-- 30.5% and 36.7% reduction in triglyceride levels, compared with baseline, among patients receiving CaPre at 12 and 26 weeks respectively, as well as 42.2% reduction in triglyceride levels among patients receiving CaPre while on background statin therapy at 12 weeks
-- Despite meaningful triglyceride lowering in the CaPre arm, the study did not reach statistical significance due to unusually large placebo effect
-- No treatment-related serious adverse events were reported in the trial
-- Audits and additional post-hoc data analyses are underway into the unexpected and inconsistent findings that may have negatively impacted the results reported in TRILOGY 1
-- Acasti now plans to seek FDA guidance prior to unblinding TRILOGY 2 data, which is expected to delay reporting of TRILOGY 2 topline results until calendar Q3, 2020
Jan D'Alvise, president and CEO of Acasti Pharma, commented, "We are making steady progress with the audit of TRILOGY 1 data and additional post-hoc analyses. This data has been very informative, and provided we have the FDA's support, any learnings we can take from this investigation that may allow us to adjust the Statistical Analysis Plan (SAP) for TRILOGY 2, gives us a better chance of accurately reflecting the clinical value that we see in CaPre. As previously noted, we have confirmed that there is established precedent for the FDA accepting post-hoc analyses of study results, assuming the analyses are transparent, well justified and well supported. We are moving as quickly as possible now to complete this work and secure a meeting with the FDA. Until we have that important meeting, we intend to keep TRILOGY 2 blinded. Consequently, we now anticipate the unblinding of the topline results for TRILOGY 2 sometime in calendar Q3 of 2020, to allow time for the FDA meeting. Accordingly, key secondary and exploratory endpoints from both TRILOGY 1 and TRILOGY 2 studies, would now be expected after the unblinding of TRILOGY 2 results. We are moving as quickly as possible and will provide material updates when available."
On January 13, 2020 the Company announced preliminary topline results for the primary endpoint (triglyceride reduction at 12 and 26 weeks) from our Phase 3 TRILOGY 1 trial for CaPre. Acasti reported a 30.5% median reduction in triglyceride (TG) 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 TGs among patients receiving CaPre while on background statin therapy at 12 weeks, compared to a 31.5% median reduction in TG levels among patients receiving placebo and on background statin therapy. In addition, the Company reported a 36.7% median reduction in TG levels among patients receiving CaPre at 26 weeks (end of the study), compared to a 28.0% median reduction in TG levels among patients receiving placebo. Both the placebo and CaPre study groups experienced significant reductions in TGs 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 was no significant difference in treatment-related serious adverse events in the trial.
The observed reductions in TG 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%. The Company noted that 5 sites out of the total 54 enrolling sites disproportionately contributed to this unusually high placebo response. These sites accounted for about 36% of the 242 patients enrolled in the TRILOGY 1 study. By comparison, TRILOGY 2 was conducted at 71 sites in Canada, Mexico and the United States with a total of 278 patients enrolled. The 5 sites that are a focus of the TRILOGY 1 investigation also participated in TRILOGY 2, however these sites accounted for only about 12% of the total patients, with the majority of these patients coming from only 3 sites.
Despite monitoring activities conducted throughout the TRILOGY 1 trial to ensure adherence to the protocol and identify protocol violations, the Company has subsequently identified some unexpected and inconsistent findings that it believes may have negatively contributed to the overall topline results. These findings are now being further explored via a comprehensive and rigorous review of data and patient medical records by an independent team of auditors. To support this effort, the Company, its independent Clinical Research Organization (CRO) that conducted the TRILOGY studies, its principal investigator Dr. Mozaffarian, and other clinical and regulatory advisors, are conducting a thorough review of all data and records from patients taking both CaPre and placebo. This assessment is well underway, and the Company has also determined that a thorough investigation of the data must be completed and reviewed with the FDA, before the Company can report the findings from TRILOGY 1 and the implications for TRILOGY 2.
Consequently, the Company intends to request a meeting with the FDA to discuss the TRILOGY 1 data, and will seek their guidance about how to conduct the analysis of the TRILOGY 2 data prior to unblinding TRILOGY 2. The Company continues to remain blinded to the TRILOGY 2 data. Upon submission of the meeting request, which is expected to be sent to the FDA in calendar Q2, 2020, the FDA will have 75 days to respond and schedule a meeting.
Given the need to complete the audit and review of the TRILOGY 1 data, and obtain FDA feedback, the Company now anticipates the unblinding of the topline results for TRILOGY 2 sometime in calendar Q3 of 2020. Acasti will provide further guidance as to the timing of reporting TRILOGY 2 data based on progress of the audits and feedback from the FDA. Accordingly, key secondary and exploratory endpoints from both TRILOGY 1 and TRILOGY 2 studies, would now be expected as soon as possible after the unblinding of TRILOGY 2 results.
If the interpretation of the analyses produced as an outcome of the TRILOGY 1 audits and post-hoc data review are supported by the FDA, and if TRILOGY 2 achieves statistical significance, Acasti believes it may still have a viable path forward to file an NDA for CaPre.
At December 31, 2019, Acasti had $25.7 million of cash, cash equivalents and marketable securities. This capital is expected to also fund the ongoing study investigations, as well as continued work on the NDA. With the Government funding, capital raised through the established at-the-market program (ATM) during Q3, recent exercise of warrants and cash on hand, the Company is sufficiently funded through December 2020, based on management's current projections.
Third Quarter Fiscal 2020 Financial Results:
Acasti also provided an update on recent distributions under its previously adopted ATM program, as required pursuant to the policies of the TSX Venture Exchange. Since the last distributions under the ATM program reported on December 23, 2019, Acasti issued an aggregate of 1,355,798 common shares of the Company (the "ATM Shares") over the NASDAQ Stock Market for aggregate gross proceeds to the Company of US$1.4 million. The ATM Shares were sold at prevailing market prices which ranged from US$2.02 per share to US$0.85 per share. No securities were sold through the facilities of the TSX Venture Exchange or, to the knowledge of the Company, in Canada. The ATM Shares were sold pursuant to a U.S. registration statement on Form F-3 (No. 333-223464) as made effective on March 16, 2018, as well as an at-the-market issuance sales agreement dated February 14, 2019 among Acasti and B. Riley FBR, Inc.