Acasti Pharma Inc. (“Acasti or the “Company”) (NASDAQ: ACST –
TSX-V: ACST), 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 (triglyceride blood levels from 500
mg/dL to 1500 mg/dL), today announced topline results for the
Primary Endpoint (triglyceride reduction at 12 and 26 weeks) from
its Phase 3 TRILOGY 1 trial for the Company's lead product
candidate, CaPre.
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. Results for
all of the secondary and exploratory endpoints were delayed as
previously reported on December 23, 2019, and are expected to be
available by the end of Q1, 2020.
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%.
A table summarizing the placebo and active
triglyceride lowering results from all of these previous
hypertriglyceridemia trials is presented below:
A Media Snippet accompanying this announcement
is available by clicking on the image or link below:
Given that cornstarch is likely not the root
cause for the significant placebo response in TRILOGY 1, the
Company is carefully evaluating other possible explanations. The
Company has noted that a high placebo response at 5 sites (out of a
total of 54 enrolling sites) disproportionately contributed to the
overall placebo response, and is being further investigated. A full
audit of these sites, including review of all raw data and records
from patients taking both CaPre and placebo, will be conducted to
identify a possible root cause of the unprecedented placebo effect.
This audit is likely to take at least several weeks, with an
outcome expected by the end of February 2020. Additional avenues of
investigation will include further assessment related to specific
continuation or discontinuation of other lipid lowering drugs
during screening, and changes in the use of other lipid-lowering
medications during the trial. Furthermore, the results of the
ongoing TRILOGY 2 trial with CaPre may provide additional important
information and insight in this regard. If one or more of these
investigations provide a plausible explanation as to what may have
influenced the placebo arm, and assuming the primary endpoint
reaches statistical significance in TRILOGY 2, the Company may
still have a path forward to file an NDA, and would seek a meeting
with the FDA as soon as possible to discuss all of the TRILOGY
data, investigational findings, and obtain their input and guidance
on next steps.
Dariush Mozaffarian, M.D., Dr.P.H., principal
investigator for the study, commented, “Compared with baseline,
triglyceride levels in subjects receiving CaPre were substantially
lower at 12 and 26 weeks in the CaPre arm, with 30.5% and 37.5%
lower levels, respectively. However, these reductions were
accompanied by larger than expected declines in triglyceride levels
in the placebo group, which remain unexplained and highly unusual.
Initial analyses suggest no protocol deviations in treatment
allocation, capsule contents, laboratory quality control, or
mismatched randomization that could explain these highly unusual
placebo results. We are continuing to evaluate the data in detail
to assess possible explanations. I am also hopeful that TRILOGY 2
topline data, expected in late January 2020, may provide more
insight into this unprecedented placebo response seen in TRILOGY
1.”
Jan D’Alvise, president and CEO of Acasti
Pharma, stated, “First, we wish to thank the physicians, study
professionals, and of course the 242 patients who dedicated their
time to participate in this trial. While we are encouraged by the
magnitude of reduction in triglyceride levels seen among patients
receiving CaPre, the large placebo effect was completely
unexpected, and was about double what was seen in all other
therapeutic OM3 hypertriglyceridemia trials. Several hypotheses are
being investigated now by our clinical team, and by our CRO and Dr.
Mozaffarian. These avenues of investigation are being
carefully and rigorously pursued, and we are moving as quickly as
possible to try to gain understanding and insight into the large
and unexpected placebo response seen in TRILOGY 1. The Company will
continue to provide updates on this investigation, as well as
topline results for TRILOGY 2 as we get them, to be followed by all
secondary and exploratory endpoints for TRILOGY 1 and 2 once the
TRILOGY 2 study is completed and fully analyzed.”
Implementation of the TRILOGY 2 study remains on
track, with the last patient having completed their final visit
late last week. The Company remains blinded to the TRILOGY 2
data. Given the additional focus of critical resources now on
TRILOGY 1, there could be a small delay of a couple weeks in
reporting topline results for TRILOGY 2 to mid-February 2020. As
previously disclosed, key secondary and exploratory endpoints from
both studies, would be expected sometime later in the first quarter
of 2020.
About
CaPre
Acasti’s prescription drug candidate, CaPre, is
a highly purified omega-3 phospholipid concentrate derived from
krill oil, and is being developed to treat severe
hypertriglyceridemia, a metabolic condition that contributes to
increased risk of cardiovascular disease and pancreatitis. Its
omega-3s, principally EPA and DHA, are either “free” or bound to
phospholipids, which allows for better absorption into the body.
Acasti believes that EPA and DHA are more efficiently transported
by phospholipids sourced from krill oil than the EPA and DHA
contained in fish oil that are transported either by triglycerides
(as in dietary supplements) or as ethyl esters in other
prescription omega-3 drugs, which must then undergo additional
digestion before they are ready for transport in the bloodstream.
Clinically, the phospholipids may not only improve the absorption,
distribution, and metabolism of omega-3s, but they may also
decrease the synthesis of LDL cholesterol in the liver, impede or
block cholesterol absorption, and stimulate lipid secretion from
bile. In two Phase 2 studies, CaPre achieved a statistically
significant reduction of triglycerides and non-HDL cholesterol
levels in patients across the dyslipidemia spectrum from patients
with mild to moderate hypertriglyceridemia (patients with TG blood
levels between 200mg/dl and 500mg/dl) to patients with severe
hypertriglyceridemia (those with TG levels above 500mg/dl).
Furthermore, in the Phase 2 studies, CaPre demonstrated the
potential to actually reduce LDL, or “bad cholesterol”, as well as
the potential to increase HDL, or “good cholesterol”, especially at
the therapeutic dose of 4 grams/day. The Phase 2 data also showed a
significant reduction of HbA1c at a 4 gram dose, suggesting that
due to its unique omega-3/phospholipid composition, CaPre may
actually improve long-term glucose metabolism. Acasti’s TRILOGY
Phase 3 program is currently underway.
About Acasti Pharma
Acasti Pharma is a biopharmaceutical innovator
advancing a potentially best-in-class cardiovascular drug, CaPre,
for the treatment of hypertriglyceridemia, a chronic condition
affecting an estimated one third of the U.S. population. Since its
founding in 2008, Acasti Pharma has focused on addressing a
critical market need for an effective, safe and well-absorbing
omega-3 therapeutic that can make a positive impact on the major
blood lipids associated with cardiovascular disease risk. The
company is developing CaPre in a Phase 3 clinical program in
patients with severe hypertriglyceridemia, a market that includes 3
to 4 million patients in the U.S. The addressable market may expand
significantly if omega-3s demonstrate long-term cardiovascular
benefits in on-going third party outcomes studies. Acasti may need
to conduct at least one additional clinical trial to support FDA
approval of a supplemental New Drug Application to expand CaPre’s
indications to this segment. Acasti’s strategy is to commercialize
CaPre in the U.S. and the company is pursuing development and
distribution partnerships to market CaPre in major countries around
the world. For more information, visit www.acastipharma.com.
Forward
Looking
Statements
Statements in this press release that are not
statements of historical or current fact constitute
“forward-looking information” within the meaning of Canadian
securities laws and “forward-looking statements” within the meaning
of U.S. federal securities laws (collectively, “forward-looking
statements”). Such forward-looking statements involve known and
unknown risks, uncertainties, and other unknown factors that could
cause the actual results of Acasti to be materially different from
historical results or from any future results expressed or implied
by such forward-looking statements. In addition to statements which
explicitly describe such risks and uncertainties, readers are urged
to consider statements labeled with the terms “believes,” “belief,”
“expects,” “intends,” “anticipates,” “potential,” “should,” “may,”
“will,” “plans,” “continue”, “targeted” or other similar
expressions to be uncertain and forward-looking. Readers are
cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this press release.
Forward-looking statements in this press release include, but are
not limited to, information or statements about Acasti’s strategy,
future operations, prospects and the plans of management; Acasti’s
ability to conduct all required clinical and non-clinical trials
for CaPre, including the timing and results of those trials; the
timing and the outcome of licensing negotiations; CaPre’s
potential to become the “best-in-class” cardiovascular drug for
treating severe Hypertriglyceridemia (HTG), Acasti’s ability to
commercially launch CaPre and to fund its continued operations,
CaPre’s potential to meet or exceed the target primary endpoint of
reducing triglycerides by 20% compared to placebo, Acasti’s ability
to report topline results for TRILOGY 2 in January 2020 as well as
Acasti’s ability to report key secondary and exploratory endpoints
from both TRILOGY studies by the end of the first quarter of 2020,
and Acasti’s ability to file an NDA based on the TRILOGY
studies.
The forward-looking statements contained in this
press release are expressly qualified in their entirety by this
cautionary statement, the “Cautionary Note Regarding
Forward-Looking Information” section contained in Acasti’s latest
annual report on Form 20-F and most recent management’s discussion
and analysis (MD&A), which are available on SEDAR at
www.sedar.com, on EDGAR at www.sec.gov/edgar/shtml, and on the
investor section of Acasti’s website at www.acastipharma.com. All
forward-looking statements in this press release are made as of the
date of this press release. Acasti does not undertake to update any
such forward-looking statements whether as a result of new
information, future events or otherwise, except as required by law.
The forward-looking statements contained herein are also subject
generally to assumptions and risks and uncertainties that are
described from time to time in Acasti’s public securities filings
with the Securities and Exchange Commission and the Canadian
securities commissions, including Acasti’s latest annual report on
Form 20-F and most recent MD&A.
Neither NASDAQ, the TSX Venture Exchange nor its
Regulation Services Provider (as that term is defined in the
policies of the TSX Venture Exchange) accepts responsibility for
the adequacy or accuracy of this release.
Acasti
Contact:
Jan D’AlviseChief Executive OfficerTel:
450-686-4555Email: info@acastipharma.com www.acastipharma.com
Investor
Contact:
Crescendo Communications, LLCTel:
212-671-1020Email: ACST@crescendo-ir.com
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