Aeterna Zentaris Announces Plans to Pursue FDA Registration of Macrilen

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.

About Macrilen (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.

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.

Source: Aeterna Zentaris Inc.