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New Medicines

Macimorelin Aeterna Zentaris (EU); Macrilen (US)Growth hormone deficiency in adults (test)

Information

Macimorelin Aeterna Zentaris (EU); Macrilen (US)
New molecular entity
Consilient Health
Aeterna Zentaris

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Launched
Yes
Dec 20Macimorelin licensed to Consilient Health in Europe and the UK. Under the terms of the Agreement, Consilient Health will be responsible for obtaining pricing and reimbursement approval in the European economic area and the UK, as well as bearing the regulatory cost for the label extension for pediatric use pending successful outcome of the upcoming safety and efficacy study, AEZS-130-P02 (Study P02), evaluating macimorelin for the diagnosis of CGHD [24].
May 20Aeterna Zentaris are seeking to secure an out-licensing agreement for the commercialisation of macimorelin in EU [22].
Jan 19EMA grants marketing authorization for macimorelin for diagnosis of AGHD [20].
Nov 18Recommended for EU approval by CHMP - the full indication is "This medicinal product is for diagnostic use only. Macimorelin Aeterna Zentaris is indicated for the diagnosis of growth hormone deficiency (GHD) in adults". It is proposed that use should be supervised by a physician or healthcare professional experienced in diagnosing growth hormone deficiency [19].
Jul 18Strongbridge Biopharma launches macimorelin for diagnosis of patients with AGHD in the US [21].
Dec 17Approved in the US "for the diagnosis of adult growth hormone deficiency"; cautions include lack of data for subjects with BMI >40 kg/m^2, risk of QT prolongation, and use with strong CYP3A4 inducers [18].
Nov 17Filed in EU via centralised procedure [17].
Jul 17Following a resubmission, the FDA has accepted the New Drug Application for macimorelin and has set a target PDUFA action date of 30th December 2017. The company are confident that it will be approved and aims for a US launch during the first quarter of 2018 [16].
Mar 17Aeterna Zentaris intends to discuss trial results with FDA - having reviewed the data, they consider that the successful result for negative agreement demonstrates support for registration [15].
Jan 16PIII trial in progress, expected to complete end 2016 [12].
Apr 15AEZS expect to receive comments from the EMA regarding the study design during a Scientific Advice Meeting in early May [11].
Apr 15AEZS met with FDA and plan a new PIII trial following a successful meeting [11].
Nov 14FDA rejected approval of growth hormone stimulant macimorelin [9].
Jan 14FDA decision on approval expected by 5 Nov 14 [8].
Nov 13Filed in the US to evaluate adult growth hormone deficiency [7].
Apr 12The company plans to file in the US during 2012 [3].
Dec 07Orphan drug status was granted in the US in 2007 [6].

Category

Ghrelin agonist, a novel orally active small molecule that stimulates the secretion of growth hormone
The prevalence of growth hormone deficiency is estimated to be between 1 in 3500 and 1 in 4000 children. In about half of the children with growth hormone deficiency (50%), the cause is unknown (idiopathic growth hormone deficiency) [10].
Growth hormone deficiency in adults (test)
Oral

Trial or other data

Mar 17Aeterna Zentaris announces that results of the PIII trial will be presented as a conference abstract on 1/4/17 (Endocrine Society 99th Annual Meeting); they hold that while the positive agreement results did not reach the criteria for a successful outcome, the negative agreement results, which met the success criteria, should be considered as the more relevant endpoint. They therefore consider that the study demonstrated that the Macrilen™ test provides medical benefit [15].
Jan 17Company announces that the confirmatory PIII trial failed its primary outcome - based on top-line data, macimorelin did not achieve equivalence to the ITT in diagnosis of adult growth hormone deficiency. The company will evaluate the full results from the trial and decide in the hear future whether macimorelin development will continue [14].
Jan 16Following meetings with FDA and EMA, trial NCT02558829 is in progress, involving about 30 centres in US and EU, estimated recruitment=110 and primary completion date Oct 2016. The macimorelin-GHST (growth hormone stimulation test) will be compared with the ITT (insulin tolerance test) in an open-label, randomized, 2-way crossover trial, including adult subjects suspected to have adult growth hormone deficiency (AGHD) and a group of healthy controls. There will be four subject groups with high, intermediate, and low likelihood of GHD, respectively, plus the healthy controls [12,13].
Apr 15AEterna Zentaris (AEZS) announce plans to initiate PIII study of macimorelin n AGHD following a successful meeting with the FDA. The meeting was requested by AEZS to gain clarity on the approval deficiencies described in the CRL the company received in November 2014. AEZS have plans to conduct a new, confirmatory PIII clinical study to demonstrate the efficacy of macimorelin. The study will be conducted as a two-way crossover with the insulin tolerance test as the benchmark comparator. The study population will consist of pts with a medical history documenting risk factors for AGHD and will include a spectrum of pts with a low to high risk of having AGHD. AEZS estimate that completion of the confirmatory Phase 3 study and the QT study will take about 18 months [11].
Nov 14FDA rejected macimorein in adult growth hormone deficiency (AGHD) after it failed to meet its primary efficacy endpoint in submitted trial results. The FDA were also concerned that macimorelin may not have been tested on patients that were demonstrably suffering from AGHD. The FDA have asked the firm to resubmit another clinical trial [9].
Oct 12PIII results presented at 6th International Congress of the Growth Hormone Research (GRS) and Insulin-like Growth Factor (IGF) Society, Munich, Germany [5].
Jun 12Final PIII results for AEZS-130 announced. Of the 53 AGHD subjects enrolled, 52 received AEZS-130, and 50 who had confirmed AGHD prior to study entry were included in this analysis, along with 48 controls. Two AGHD subjects could not be matched due to the combination of young age, high body mass index (BMI) and estrogen use. Mean peak growth hormone (GH) levels in AGHD pts and controls following AEZS-130 administration were 2.36ng/mL (range 0.03-33) and 17.71ng/mL (range 10.5-94), respectively. The receiver operating characteristic (ROC) plot analysis yielded an optimal GH cut-point of 2.7ng/mL, with 82% sensitivity, 92% specificity and a 13% misclassification rate. Obesity (BMI>30) was present in 58% of cases and controls, and peak GH levels were inversely associated with BMI in controls. Adverse events were seen in 37% of AGHD pts and in 21% of controls following AEZS-130. In contrast, 61% of AGHD subjects and 30% of controls experienced AEs with L-ARG+GHRH. The most common AEs after AEZS-130 were unpleasant taste (19.2%) and diarrhea (3.8%) for the AGHD patients and unpleasant taste (4.2%) and diarrhea (4.2%) for the matched controls. AEs were generally mild or moderate in severity. Data showed AEZS-130 to be safe and effective in diagnosing AGHD [4].
Aug 11Aeterna Zentaris Inc. announced favourable top-line results of its completed Phase 3 study with AEZS-130; the results show that AEZS-130 reached its primary endpoint demonstrating >90% area-under-the-curve (AUC) of the Receiver Operating Characteristic (ROC) curve, which determines the level of specificity and sensitivity of the product. In addition, 8 of the 10 newly enrolled AGHD pts were correctly classified by a pre-specified peak GH threshold level. AEZS-130 was shown to be safe and well tolerated
Jul 11PIII study completed with AEZS 130 as the first oral diagnostic test for adult growth hormone deficiency (AGHD). The first part of the study was a 2-way crossover study (n=42) comparing 1mcg/kg (max 100mcg) GHRH + 30g arginine IV over 30 mins, with 0.5mg/kg AEZS 130 in an oral solution of 0.5mg/mL. For the second part of the study: an additional 30 normal control pts were recruited to match the original control cohort, and an additional 20 pts were recruited (10 AGHD and 10 normal control), (total n=100). All pts received 0.5mg/kg AEZS 130 [1].

Evidence based evaluations