Aeterna Zentaris has 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.”