Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the “Company”)
today announced that, following a comprehensive review of data
obtained from the confirmatory Phase 3 clinical trial of Macrilen™
(macimorelin) for the evaluation of growth hormone deficiency in
adults (“AGHD”), using the insulin tolerance test (the “ITT”) as a
comparator, it concluded that Macrilen™ demonstrated performance
supportive of achieving registration with the U.S. Food and Drug
Administration (the “FDA”). The FDA has agreed to consider the
Company’s conclusions during a Type A meeting, which is currently
being scheduled.
Following a comprehensive analysis of the data from the
confirmatory trial, the Company concluded as follows:
- Macrilen™ stimulates the pituitary
gland to produce growth hormone more effectively than the ITT; in
approximately 80% of all patients, measured growth hormone levels
following the administration of Macrilen™ were equal to or higher
than the growth hormone levels produced by the ITT;
- The Macrilen™ test performed well in
the study:
- Sensitivity (87%) and specificity (96%)
of the Macrilen™ test were satisfactory;
- Data of the previous study (82%
sensitivity, 92% specificity) could be reproduced;
- The co-primary endpoint “negative
agreement” with the ITT, which is considered as the more relevant
endpoint, was met, demonstrating that the Macrilen™ test provides
medical benefit;
- The co-primary endpoint “positive
agreement” with the ITT was not met;
- In the repeatability part of the study,
conducted upon request of the European Medicines Agency, Macrilen™
results proved to be highly reproducible:
- 94% reproducibility (32 out of 34 cases
at the cut-off point defined in the study protocol);
- Reproducibility of the ITT, which was
not investigated in this study, appears worse than the Macrilen™
test as demonstrated by a high number of non-evaluable ITTs in the
study;
- Study results can be further optimized
by modulation of the pre-defined cut-off point of 2.8 ng/mL:
- Any cut-off point for Macrilen™ between
4.6 ng/mL and 8.6 ng/mL would have resulted in a positive study
outcome in that both protocol-defined co-primary endpoints would
have been met; and
- The dose of Macrilen™ used in the study
was adequate and appropriate.
Commenting on the Company’s review of the data, Dr. Richard
Sachse, the Company’s Chief Scientific Officer, stated, “Macrilen™
stimulated the pituitary gland more powerfully than the ITT and
demonstrated good specificity and sensitivity in this study, thus
reproducing the results of our previous study. In our confirmatory
study, we demonstrated that Macrilen™ achieves a high degree of
correlation with the ITT, which could be further optimized when a
higher cut-off point, such as the ITT cut-off point, is used for
the Macrilen™ test. We believe that such an increased cut-off point
would be justified by the more powerful stimulation of MacrilenTM
as compared to the ITT. We look forward to having a discussion with
the regulatory authorities regarding our conclusions and hope that
they will concur with us. The ITT is inconvenient for patients and
physicians and contraindicated in certain patients, such as
patients with coronary heart disease or seizure disorder, requiring
the patient to experience hypoglycemia to obtain a result. Patients
and physicians need and deserve a better option than the ITT.”
David A. Dodd, President and Chief Executive Officer of the
Company stated, “We are delighted to report these successful and
impressive results following a comprehensive analysis of the data
from our confirmatory trial. We look forward to upcoming
discussions with the FDA and, hopefully, to the subsequent
registration and commercialization of Macrilen™ in the U.S.,
providing a much needed new option and alternative to the ITT.”
About the Study
The confirmatory Phase 3 clinical study of Macrilen™, entitled
Confirmatory validation of oral macimorelin as a growth hormone
(GH) stimulation test (ST) for the diagnosis of adult growth
hormone deficiency (AGHD) in comparison with the insulin tolerance
test (ITT), was designed as a two-way crossover study with the ITT
as the benchmark comparator and involved some 26 sites in the U.S.
and Europe. The trial involved 157 subjects, of whom 140 completed
two evaluable tests for AGHD using both Macrilen™ and the ITT.
Thirty-four of the patients were evaluated using Macrilen™ a second
time to measure the repeatability of the result obtained using
Macrilen™ as the evaluation method. The study population consisted
of 115 patients who were suspected of having AGHD as a result of
the presence of one or more symptoms or risk factors. This segment
of the population included a range of patients from those
considered at low risk of having AGHD to those considered at high
risk. The study population also included 25 healthy subjects, who
had no risk of having AGHD. Under the study protocol, the
evaluation of AGHD with Macrilen™ will be considered successful, if
the lower bound of the two-sided 95% confidence interval (or lower
bound of the one-sided 97.5% confidence interval) for the primary
efficacy variables is 75% or higher for “percent negative
agreement,” and 70% or higher for the “percent positive agreement.”
Based on meetings with the FDA as well as the European Medicines
Agency (“EMA”) and subsequent written scientific advice, the
Company believes that the study meets the FDA’s and the EMA’s
study-design expectations allowing U.S. and European approval, if
successful. Dr. Jose M. Garcia, MD, PhD, an Associate Professor of
Medicine at the Puget Sound VA Hospital and the University of
Washington in Seattle, was the principal investigator of the
confirmatory Phase 3 clinical trial. More details about the trial
are available at the following link:
https://www.clinicaltrials.gov/ct2/show/NCT02558829?term=macimorelin&rank=1.
About MacrilenTM (macimorelin)
Macimorelin, a ghrelin agonist, is an orally-active small
molecule that stimulates the secretion of growth hormone.
Macimorelin has been granted orphan drug designation by the FDA for
diagnosis of AGHD. The Company owns the worldwide rights to this
patented compound and has significant patent protection left. The
Company’s U.S. composition of matter patent expires in 2022 and its
U.S. utility patent runs through 2027. The Company proposes,
subject to FDA approval, to market macimorelin under the tradename
Macrilen™.
About AGHD
AGHD affects approximately 75,000 adults across the U.S., Canada
and Europe. Growth hormone not only plays an important role in
growth from childhood to adulthood, but also helps promote a
hormonally-balanced health status. AGHD mostly results from damage
to the pituitary gland. It is usually characterized by a reduction
in bone mineral density, lean body mass, exercise capacity, and
overall quality of life as well as an increase of cardiovascular
risks.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a specialty biopharmaceutical company
engaged in developing and commercializing novel treatments in
oncology, endocrinology and women’s health. We are engaged in drug
development activities and in the promotion of products for others.
We recently completed Phase 3 studies of two internally developed
compounds. The focus of our business development efforts is the
acquisition of licenses to products that are relevant to our
therapeutic areas of focus. We also intend to license out certain
commercial rights of internally developed products to licensees in
non-U.S. territories where such out-licensing would enable us to
ensure development, registration and launch of our product
candidates. Our goal is to become a growth-oriented specialty
biopharmaceutical company by pursuing successful development and
commercialization of our product portfolio, achieving successful
commercial presence and growth, while consistently delivering value
to our shareholders, employees and the medical providers and
patients who will benefit from our products. For more information,
visit www.aezsinc.com.
Forward-Looking Statements
This press release contains forward-looking statements made
pursuant to the safe harbor provision of the U.S. Securities
Litigation Reform Act of 1995, which reflect our current
expectations regarding future events. Forward-looking statements
may include, but are not limited to statements preceded by,
followed by, or that include the words “expects,” “believes,”
“intends,” “anticipates,” and similar terms that relate to future
events, performance, or our results. Forward-looking statements
involve known risks and uncertainties, many of which are discussed
under the caption “Key Information – Risk Factors” in our most
recent Annual Report on Form 20-F filed with the relevant Canadian
securities regulatory authorities in lieu of an annual information
form and with the U.S. Securities and Exchange Commission (“SEC”).
Such statements include, but are not limited to, statements about
the progress of our research, development and clinical trials and
the timing of, and prospects for, regulatory approval and
commercialization of our product candidates, the timing of expected
results of our studies, anticipated results of these studies,
statements about the status of our efforts to establish a
commercial operation and to obtain the right to promote or sell
products that we did not develop and estimates regarding our
capital requirements and our needs for, and our ability to obtain,
additional financing. Known and unknown risks and uncertainties
could cause our actual results to differ materially from those in
forward-looking statements. Such risks and uncertainties include,
among others, the availability of funds and resources to pursue our
research and development projects and clinical trials, the
successful and timely completion of clinical studies, the risk that
safety and efficacy data from any of our Phase 3 trials may not
coincide with the data analyses from previously reported Phase 1
and/or Phase 2 clinical trials, the rejection or non-acceptance of
any new drug application by one or more regulatory authorities and,
more generally, uncertainties related to the regulatory process
(including whether or not the regulatory authorities will accept
the Company’s conclusions regarding Macrilen™ following its
comprehensive review of the Phase 3 study data described elsewhere
in this presentation), the ability of the Company to efficiently
commercialize one or more of its products or product candidates,
the degree of market acceptance once our products are approved for
commercialization, our ability to take advantage of business
opportunities in the pharmaceutical industry, our ability to
protect our intellectual property, and the potential of liability
arising from shareholder lawsuits and general changes in economic
conditions. Investors should consult the Company’s quarterly and
annual filings with the Canadian securities commissions and the SEC
for additional information on risks and uncertainties. Given these
uncertainties and risk factors, readers are cautioned not to place
undue reliance on these forward-looking statements. We disclaim any
obligation to update any such factors or to publicly announce any
revisions to any of the forward-looking statements contained herein
to reflect future results, events or developments, unless required
to do so by a governmental authority or applicable law.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170213005054/en/
Aeterna Zentaris Inc.Philip A. Theodore, 843-900-3223Senior Vice
Presidentir@aezsinc.com
Aeterna Zentaris (NASDAQ:AEZS)
Historical Stock Chart
From Aug 2024 to Sep 2024
Aeterna Zentaris (NASDAQ:AEZS)
Historical Stock Chart
From Sep 2023 to Sep 2024