- Cardiovascular Death Reduced by 20%
- Fatal or Nonfatal Heart Attacks Reduced by
31%
- Fatal or Nonfatal Stroke Reduced by 28%
- Urgent or Emergent Coronary Revascularization Reduced by
35%
- Hospitalization for Unstable Angina Reduced by
32%
- Number Needed to Treat for Primary Composite Endpoint:
21
- HLS has the Exclusive Rights to Vascepa for the Canadian
Market
TORONTO, Nov. 12, 2018 /CNW/ - HLS Therapeutics Inc.
("HLS" or the "Company") (TSX-V:HLS) announces that Amarin
Corporation plc (NASDAQ:AMRN) released primary results from
the Vascepa® (icosapent ethyl) cardiovascular ("CV")
outcomes trial, REDUCE-IT™, at the 2018 Scientific Sessions of the
American Heart Association ("AHA") in Chicago, Illinois on Saturday November 10, 2018. REDUCE-IT
primary results confirmed 25% relative risk reduction ("RRR") for
the topline primary endpoint result with multiple robust
demonstrations of efficacy, including 20% reduction in
cardiovascular death. HLS has in-licensed the exclusive rights to
Vascepa for the Canadian market. Vascepa has not been submitted to
Health Canada for regulatory approval and is not approved for use
in Canada.
Cardiovascular benefits appeared not to be influenced
significantly by triglyceride ("TG") levels at baseline (135 mg/dL
to 499 mg/dL baseline range) or as achieved at one year, suggesting
mechanisms at work with use of Vascepa that are independent of
triglyceride reduction. Results were robust across multiple
subgroups, including in patients with and without diabetes at
baseline. REDUCE-IT study results were simultaneously published in
The New England Journal of Medicine and are available at
nejm.org/doi/full/10.1056/NEJMoa1812792.
REDUCE-IT was a global study of 8,179 statin-treated adults with
elevated CV risk. Many patients with well-managed LDL-C remain at
high risk for cardiovascular events. No therapy is currently
approved to treat the residual risk in REDUCE-IT patients.
REDUCE-IT studied Vascepa 4 grams/day as compared to placebo over a
median follow-up time of 4.9 years.
The results from the REDUCE-IT study presented by Amarin and the
New England Journal of Medicine over the weekend are as
follows:
Primary endpoint achieved: 25% relative risk reduction
(RRR) (hazard ratio (HR), 0.75; 95% confidence interval CI,
0.68-0.83; p<0.001) in first occurrence of major adverse CV
events (MACE) in the intent-to-treat population consisting of a
composite of cardiovascular death, nonfatal myocardial infarction
(MI or heart attack), nonfatal stroke, coronary revascularization
(procedures such as stents and by-pass) and unstable angina
requiring hospitalization. Number needed to treat ("NNT") was
21 for the first occurrence of MACE in the 5-point primary
composite endpoint.
Key secondary endpoint achieved: 26% RRR (HR, 0.74; 95%
CI, 0.65-0.83; p<0.001) in 3-point MACE in the intent-to-treat
population consisting of a composite of cardiovascular death,
nonfatal heart attack and nonfatal stroke.
Additional secondary endpoints achieved: Seven secondary
endpoints were achieved below the key secondary endpoint, as
follows (in order of sequential statistical testing within the
prespecified hierarchy):
- Cardiovascular death or nonfatal heart attack: 25% RRR
(HR, 0.75; 95% CI, 0.66-0.86; p<0.001)
- Fatal or nonfatal heart attack: 31% RRR (HR, 0.69; 95%
CI, 0.58-0.81; p<0.001)
- Urgent or emergent revascularization: 35% RRR (HR, 0.65;
95% CI, 0.55-0.78; p<0.001)
- Cardiovascular death: 20% RRR (HR, 0.80; 95% CI,
0.66-0.98; p=0.03)
- Hospitalization for unstable angina: 32% RRR (HR, 0.68;
95% CI, 0.53-0.87; p=0.002)
- Fatal or nonfatal stroke: 28% RRR (HR, 0.72; 95% CI,
0.55-0.93; p=0.01)
- Total mortality, nonfatal heart attack or nonfatal stroke:
23% RRR (HR, 0.77; 95% CI, 0.69-0.86; p<0.001)
The next prespecified secondary endpoint in the hierarchy, and
the only such endpoint that did not achieve statistical
significance, is as follows:
- Total mortality, which includes mortality from
non-cardiovascular and cardiovascular events: 13% RRR (HR, 0.87;
95% CI, 0.74-1.02; p=0.09)
Baseline demographics: Patients qualified to enroll in REDUCE-IT
had LDL-C between 41-100 mg/dL (median baseline LDL-C 75 mg/dL)
controlled by statin therapy and various cardiovascular risk
factors including persistent elevated triglycerides (TGs) between
135-499 mg/dL (median baseline 216 mg/dL) and either established
cardiovascular disease (secondary prevention cohort) or age 50 or
more with diabetes mellitus and at least one other CV risk factor
(primary prevention cohort). Approximately 59% of the patients had
diabetes at baseline and approximately 71% of the patients had
established cardiovascular disease at time of enrollment.
Safety: Excluding the major adverse CV events (MACE) results
described above, the overall adverse event rates reported by Amarin
in REDUCE-IT were similar across the statin plus Vascepa and the
statin plus placebo treatment groups. There were no significant
differences between treatments in the overall rate of treatment
emergent adverse events or serious adverse events leading to
withdrawal of study drug. The one serious adverse event occurring
at a frequency of >2% was pneumonia which occurred at a
numerically higher rate in the statin plus placebo treatment group
(2.9%) than in the statin plus Vascepa treatment group (2.6%).
Adverse events occurring in 5% or greater of patients and more
frequently with Vascepa than placebo were peripheral edema (6.5%
Vascepa patients versus 5.0% placebo patients), constipation (5.4%
Vascepa patients versus 3.6% placebo patients), and atrial
fibrillation (5.3% Vascepa patients versus 3.9% placebo patients).
There were numerically more serious adverse events related to
bleeding in the statin plus Vascepa treatment group although
overall rates were low with no fatal bleeding observed in either
group and no significant difference in adjudicated hemorrhagic
stroke or serious central nervous system or gastrointestinal
bleeding events between treatments.
Subgroups and other REDUCE-IT information reported by Amarin:
Positive REDUCE-IT results were consistent across various patient
subgroups, including female/male, diabetic/non-diabetic and
secondary/primary prevention. At baseline, approximately 59%
and 71% of the patients had diabetes and established cardiovascular
disease, respectively. Approximately 71% of the patients studied
were classified as Westernized with the largest cohort from
the United States. Vital status
was obtained for 99.8% of the patients randomized supporting robust
trial results.
"We have known for many years that controlling LDL-cholesterol
levels reduces the risk of major cardiovascular events which is why
it was important to study patients who are stabilized on statin
medications, and yet still have residual risk factors such as high
triglycerides," said Dr. Jean-Claude
Tardif, Director of the Montreal Heart Institute Research
Centre and Steering Committee member for the REDUCE-IT®
clinical trial. "The REDUCE-IT® study gives us new
evidence that icosapent ethyl (EPA) can further contribute to the
prevention of a major cardiovascular event in these patients."
"I want to congratulate the entire team at Amarin for having run
an exceptional trial that has generated positive results which we
believe will deliver benefits to millions of cardiac patients for
years to come," said Greg Gubitz,
CEO of HLS Therapeutics. "Cardiovascular disease is the leading
cause of death worldwide, so we look forward to bringing this
important and proven preventative medication to the many patients
in Canada who stand to benefit
from it."
For more information on Vascepa and the REDUCE-IT trial, please
see the press release issued November 10,
2018, by Amarin, which can be found at:
http://investor.amarincorp.com/press-releases
REGULATORY PATHWAY
Vascepa has not been approved for
use in Canada, and its safety and
effectiveness are still under investigation. HLS intends to submit
a New Drug Submission to Health Canada in early 2019 seeking
approval for Vascepa based on the results of the REDUCE-IT study
and other previous trials.
ABOUT CARDIOVASCULAR DISEASE
Worldwide, cardiovascular
disease (CVD) remains the #1 killer of men and women.
Multiple primary and secondary prevention trials have
shown a significant reduction of 25% to 35% in the risk
of cardiovascular events with statin therapy,
leaving significant persistent residual risk despite the
achievement of target LDL-C levels.1
Beyond the cardiovascular risk associated with LDL-C, genetic,
epidemiologic, clinical and real-world data suggest that patients
with elevated triglycerides (TG) (fats in the blood), and TG-rich
lipoproteins, are at increased risk for cardiovascular disease.
2, 3, 4, 5
IMPORTANT CAUTIONARY INFORMATION ABOUT REDUCE-IT PRIMARY
RESULTS
Further REDUCE-IT data assessment and data release
could yield additional useful information to inform greater
understanding of the trial outcome. Further detailed data
assessment by Amarin and regulatory authorities will continue and
take several months to complete and record. The final evaluation of
the totality of the efficacy and safety data from REDUCE-IT may
include some or all of the following, as well as other
considerations: new information affecting the degree of treatment
benefit on studied endpoints; study conduct and data robustness,
quality, integrity and consistency; additional safety data
considerations and risk/benefit considerations; consideration of
REDUCE-IT results in the context of other clinical studies.
ABOUT HLS THERAPEUTICS INC.
Formed in 2015, HLS is a
specialty pharmaceutical company focused on the acquisition and
commercialization of late stage development, commercial stage
promoted and established branded pharmaceutical products in the
North American markets. HLS's focus is on products targeting the
central nervous system and cardiovascular therapeutic areas. HLS's
management team is composed of seasoned pharmaceutical executives
with a strong track record of success in these therapeutic areas
and at managing products in each of these lifecycle stages.
Neither 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.
FORWARD LOOKING INFORMATION
This release includes
forward-looking statements regarding HLS and its business. Such
statements are based on the current expectations and views of
future events of HLS's management. In some cases the
forward-looking statements can be identified by words or phrases
such as "may", "will", "expect", "plan", "anticipate", "intend",
"potential", "estimate", "believe" or the negative of these terms,
or other similar expressions intended to identify forward-looking
statements, including, among others, statements with respect to
HLS's pursuit of additional product and pipeline opportunities in
certain therapeutic markets, statements regarding growth
opportunities and expectations regarding financial performance. The
forward-looking events and circumstances discussed in this release
may not occur and could differ materially as a result of known and
unknown risk factors and uncertainties affecting HLS, including
risks relating to the specialty pharmaceutical industry, risks
related to the regulatory approval process, economic factors and
many other factors beyond the control of HLS. Forward-looking
statements and information by their nature are based on assumptions
and involve known and unknown risks, uncertainties and other
factors which may cause HLS's actual results, performance or
achievements, or industry results, to be materially different from
any future results, performance or achievements expressed or
implied by such forward-looking statement or information.
Accordingly, readers should not place undue reliance on any
forward-looking statements or information. A discussion of the
material risks and assumptions associated with this release can be
found in the Company's Annual Information Form dated October 26, 2018, which has been filed on SEDAR
and can be accessed at www.sedar.com. Accordingly, readers should
not place undue reliance on any forward-looking statements or
information. Except as required by applicable securities laws,
forward-looking statements speak only as of the date on which they
are made and HLS undertakes no obligation to publicly update or
revise any forward-looking statement, whether as a result of new
information, future events, or otherwise.
REFERENCES
1 Ganda
OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive
dyslipidemia therapy in hypertriglyceridemia management. J Am
Coll Cardiol. 2018;72(3):330-343.
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2 Budoff
M. Triglycerides and triglyceride-rich lipoproteins in the causal
pathway of cardiovascular disease. Am J Cardiol.
2016;118:138-145.
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3 Toth PP,
Granowitz C, Hull M, et al. High triglycerides are associated with
increased cardiovascular events, medical costs, and resource use: A
real-world administrative claims analysis of statin-treated
patients with high residual cardiovascular risk. J Am Heart
Assoc. 2018;7(15):e008740.
|
4
Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic
cardiovascular disease - New insights from epidemiology, genetics,
and biology. Circ Res. 2016;118:547-563.
|
5
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease.
Lancet. 2014;384:626–635.
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SOURCE HLS Therapeutics Inc.