Acasti Pharma Inc (NASDAQ:ACST) (CVE:ACST) said it is looking forward to seeing the results from its TRILOGY 2 trial on its flagship drug candidate CaPre as it outlined the findings of a 'rigorous' review of data from its TRILOGY 1 trial, which as previously reported did not reach statistical significance due to the unusually large placebo effect.
In a wide-ranging statement on Monday, the biopharma group issued an update on its Phase 3 TRILOGY program along with its fiscal results for the year to March 31.
READ: Acasti Pharma considering FDA's comments after receiving response to its CaPre TRILOGY trials briefing package
The 12 months saw steady progress, the group said, and it completed the TRILOGY Phase 3 trials in the fourth quarter, while also scaled-up its manufacturing, new drug application (NDA) preparation, and marketing aims.
The firm's CaPre drug is aimed at treating hypertriglyceridemia, or high levels of triglycerides in the blood, which is known to contribute to heart disease.
Despite positive results in the CaPre group, the TRILOGY 1 trial failed to reach statistical significance due to an unusually large placebo response of 27.5% and 28 % median reductions in the triglyceride levels at 12 and 26 weeks respectively.
Principal Investigator of TRILOGY 1, Dr Dariush Mozaffarian said that the originally observed large reduction in triglyceride (TG) in the placebo group had been "extremely unusual" before going on to explain the phenomenon of 'Pre-randomization TG Normalization'.
In simple terms, this is the "rapid, significant and sustained reduction" in triglyceride levels between screening (during qualification to take part in the trial) of patients and the time of patient randomization, when they were either started on the drug or placebo.
"For unclear reasons, perhaps regression to the mean, many of the patients in the placebo group experienced large reductions in TG even before being randomized. Use of the single baseline TG value at the time of randomization, in a post-hoc analysis, greatly attenuated and appears to explain much of this unusual placebo response. We look forward to the results of TRILOGY 2, which will further clarify the TG lowering effects of CaPre," said Dr Mozaffarian.
Based on these observations, Acasti reckons that pre-randomization TG normalization substantially impacted the outcome of TRILOGY 1, and the "ability of the study to accurately determine the therapeutic impact of CaPre as measured by the pre-specified primary endpoint".
Jan D'Alvise, CEO of Acasti, also told investors in the statement: "We are carefully considering the FDA’s comments on the TRILOGY 1 data, and are conducting further post-hoc analysis based on their feedback.
"Acasti will now finalize the Statistical Analysis Plan (SAP) for TRILOGY 2, which we plan to submit to the FDA by the end of July. We continue to remain blinded to the TRILOGY 2 data, and we continue to estimate that we should be able to report topline data by the end of August 2020. The key secondary and exploratory endpoints from both TRILOGY 1 and TRILOGY 2 trials would still be expected as soon as possible after the unblinding of TRILOGY 2 results.”
D’Alvise also highlighted that the group continued to make good progress on its preparation of an NDA package, and plans for commercial launch in the United States, if regulatory approval for CaPre is received.
"We are pleased to have been awarded additional composition of matter and method of use patents in Canada, United States, Mexico, China, Hong Kong, Chile, and Israel since the start of fiscal 2020," she added.
In its year to end March, Acasti posted a net loss of C$25.5 million or C$0.30 per share, compared to a loss of C$39.4 million or C$0.73 per share for fiscal 2019. Research and development (R&D) expenses before depreciation, amortization and stock-based compensation expenses came in at C$13.2 million, compared to C$26.9 million for the year ended March 31, 2019.
Cash and equivalents and short-term investments totaled C$14.2 million as of March 31, compared to C$25.8 million as at end of March, 2019.
Acasti shares slipped 7.9% in early trading in Toronto to stand at C$0.70 each.
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