Aeterna Zentaris, is a specialty biopharmaceutical company, has received a complete response letter (CRL) from the FDA for its NDA for Macrilen (macimorelin), a novel orally-active ghrelin agonist, for use in evaluating adult growth hormone deficiency (AGHD). Based on its review, the FDA has determined that the NDA cannot be approved in its present form.
The CRL mentions that the planned analysis of the company's pivotal trial did not meet its stated primary efficacy objective as agreed to in the special protocol assessment agreement letter between the company and the FDA. The CRL further mentioned issues related to the lack of complete and verifiable source data for determining whether patients were accurately diagnosed with 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.
The FDA concluded that, "in light of the failed primary analysis and data deficiencies noted, the clinical trial does not by itself support the indication." To address the deficiencies identified above, the CRL states that the company will need to demonstrate the efficacy of macimorelin as a diagnostic test for growth hormone deficiency in a new, confirmatory clinical study.
The CRL also outlined that a serious event of electrocardiogram QT interval prolongation occurred for which attribution to drug could not be excluded. Therefore, a dedicated thorough QT study to evaluate the effect of macimorelin on the QT interval would be necessary.
David Dodd, chairman and CEO at Aeterna Zentaris, said, "Following the FDA's decision, we currently are reviewing the outstanding issues stated in the CRL in order to evaluate our options and future plans for Macrilen."