FDA Approves Aeterna Zentaris' Macimorelin Growth Hormone Deficiency Test

The US Food and Drug Administration has announced the approval of macimorelin (Macrilen), an orally available ghrelin agonist that’s used in the diagnosis of patients with adult growth hormone deficiency (AGHD).

The orally-active small molecule, Macrilen, stimulates the secretion of growth hormone from the pituitary gland into the circulatory system. Stimulated growth hormone levels are then measured via 4 blood samples for a duration of 90 minutes, after patients received oral administration of Macrilen.

“Clinical studies have demonstrated that growth hormone stimulation testing for AGHD with oral Macrilen is reliable, well-tolerated, reproducible, safe and a much simpler test to conduct than currently available options,” Kevin Yuen, MD, clinical investigator and neuroendocrinologist, Barrow Neurological Institute, medical director, Barrow Neuroendocrinology Clinic, said. “The availability of Macrilen will greatly relieve the burden of endocrinologists in reliably and accurately diagnosing AGHD.”

Prior to the FDA approval, the gold standard for evaluation of AGHD was the insulin tolerance test (ITT), an intravenous test that requires several blood draws throughout several hours. The test, inconvenient for patients and medical practitioners, may contraindicate in patients with coronary heart disease or seizure disorder since it requires the patient to experience hypoglycemia to obtain an accurate result.

“In the absence of an FDA-approved diagnostic test for AGHD, Macrilen fills an important gap and addresses a medical need for a convenient test that will better serve patients and health providers,” Michael V. War, chief executive officer, Aeterna Zentaris,

Aeterna Zentaris resubmitted a New Drug Application (NDA) for Macrilen in June after receiving a complete response letter rejecting the therapy in November 2014.

The FDA approval is based off the confirmatory phase 3 clinical study of Macrilen which was designed as a 2-way crossover study with the ITT as a benchmark comparator.

The study involved 157 subjects, of whom 140 completed 2 tests evaluating for AGHD using both Macrilen and the ITT.

Findings indicated that Macrilen stimulated the pituitary gland to produce the growth hormone more effectively than the ITT. Approximately 80% of patients measured growth hormone levels following the administration of Macrilen that were equal to or higher than the growth hormone levels produced by the ITT.

The Macrilen test performed well in the study, approximately 87% sensitivity and 86% specificity were satisfactory. The co-primary endpoint of achieving negative agreement with the ITT was met, demonstrating that Macrilen provides medical benefit.

Thirty-four of the patients were evaluated a second time using Macrilen, measuring the repeatability of the result originally obtained using the Macrilen.

Study results can be optimized by modulation of the pre-defined cut-off point of 2.8 ng/mL, where 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. The dose used in the study was adequate and appropriate.

Aeterna Zentaris intends to make the therapy market available in the US in the first quarter of 2018.