Macimorelin

An orally active peptidomimetic ghrelin receptor agonist, FDA approved since 2017 as Macrilen, a single-dose oral solution used as a growth hormone stimulation test to diagnose adult growth hormone deficiency.

Also referenced as: Macrilen, Ghryvelin, AEZS-130, EP-01572, EP1572, JMV 1843, ARD-07, Macimorelin acetate

Also appears in: Hormone

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What is Macimorelin?

Macimorelin is a synthetic, orally active agonist of the growth hormone secretagogue receptor (the ghrelin receptor, GHSR-1a). It is not a conventional peptide: it is a peptidomimetic pseudo-tripeptide built from aminoisobutyric acid, D-tryptophan, and a gem-diamino tryptophan unit capped with a formyl group (written Aib-D-Trp-D-gTrp-CHO), with a free-base formula of C26H30N6O3 and a molecular weight of about 474.6 g/mol. The gem-diamino backbone replaces a normal peptide bond, which is what lets the molecule survive the gut and act after swallowing, something ghrelin and the peptidyl secretagogues cannot do.

The compound was designed at the University of Montpellier and CNRS as JMV 1843, carried into the clinic by Europeptides as EP-01572, and developed by Aeterna Zentaris as AEZS-130. The FDA approved it on December 20, 2017 as Macrilen (macimorelin acetate for oral solution), the only orally administered growth hormone stimulation test with a US approval, for the diagnosis of adult growth hormone deficiency. The EU authorized the same product on January 11, 2019; it is marketed there as Ghryvelin. It appears in peptide discussions for that reason, but its approved role is to provoke a measurable growth hormone surge once in a diagnostic setting, not to be taken as a therapy.

How it works

Macimorelin binds and activates GHSR-1a on somatotroph cells in the anterior pituitary and on neurons in the hypothalamus, triggering a pulse of growth hormone release. In a person with an intact pituitary the pulse is large; in someone with growth hormone deficiency it is blunted or absent, and the size of the peak is what the test reads.

• Ghrelin-receptor agonism with ghrelin-like potency — in binding assays on animal and human tissue, EP1572 matched the receptor potency of ghrelin and of the peptidyl secretagogues, and in preliminary first-in-human data from two volunteers a single oral dose as low as 0.06 mg/kg produced a strong, reproducible, growth-hormone-selective response (Broglio et al., Journal of Endocrinological Investigation, 2002, 25(8):RC26–RC28).
• A gem-diamino backbone engineered for oral activity — the medicinal chemistry series that produced JMV 1843 was built on a gem-diamino scaffold derived from EP-51389, screened for growth-hormone release that exceeded hexarelin in rats, and then confirmed for oral activity in beagle dogs before clinical selection (Guerlavais et al., Journal of Medicinal Chemistry, 2003, 46(7):1191–1203).
• Rapid absorption, short exposure — in healthy men, oral and intraduodenal dosing produced rapid, dose-dependent plasma concentrations and potent growth hormone release (Piccoli et al., Journal of Clinical Endocrinology & Metabolism, 2007, 92(5):1814–1820). The FDA label reports peak plasma concentrations between 0.5 and 1.5 hours, a terminal half-life of about 4.1 hours, metabolism mainly through CYP3A4, and a liquid meal cutting peak concentration by 55% and total exposure by 49%.
• Resolved receptor structure — cryo-electron microscopy structures of GHSR bound to macimorelin and to anamorelin, each in complex with its G protein, have defined how the two approved ghrelin mimetics occupy the orthosteric pocket (Wang et al., Acta Pharmacologica Sinica, 2025, 46(11):2998–3008).

Research status

Macimorelin’s evidence base is that of a diagnostic agent: its trials measure agreement with other stimulation tests, not clinical outcomes.

Pivotal adult studies. The first validation study (NCT00448747) enrolled 50 adults with growth hormone deficiency and 48 matched controls and compared macimorelin with arginine plus GHRH. At a peak growth hormone cut point of 2.7 ng/mL, sensitivity was 82% and specificity 92%; receiver operating characteristic areas were 0.99 for macimorelin versus 0.94 for the comparator among subjects who had both tests. The comparator GHRH product (Geref Diagnostic) became unavailable in the United States partway through enrollment, so the study finished with macimorelin alone. Peak growth hormone was inversely related to body mass index, and the single drug-related serious adverse event was an asymptomatic QT prolongation (Garcia et al., Journal of Clinical Endocrinology & Metabolism, 2013, 98(6):2422–2429). The FDA issued a complete response letter dated November 5, 2014 on the original application, asking for a confirmatory study against the insulin tolerance test and a thorough QT study.

That confirmatory study (NCT02558829) was a randomized, open-label crossover in 157 adults stratified by pre-test likelihood of deficiency plus healthy controls, with paired data on 140. Using the prespecified cut points of 2.8 ng/mL for macimorelin and 5.1 ng/mL for the insulin tolerance test, negative agreement was 94% and positive agreement 74% overall, falling to 93% and 61% in the intermediate- and low-likelihood groups. One of 154 macimorelin tests failed for technical reasons, against 27 of 157 insulin tolerance tests that failed because adequate hypoglycemia could not be induced; test-retest reproducibility for macimorelin was 97% in the published analysis (the label reports 91.2% agreement in 34 retested subjects). When a 5.1 ng/mL cut point was applied to both tests, sensitivity was 92% and specificity 96% (Garcia et al., Journal of Clinical Endocrinology & Metabolism, 2018, 103(8):3083–3093). Post hoc analyses found performance unaffected by age, sex, or body mass index within the enrolled range, with 5.1 ng/mL again the best-performing cut point (Garcia et al., Endocrine Connections, 2021, 10(1):76–83). The published and labeled cut points therefore differ, and a 2026 single-center series of 37 patients found that 40.5% met deficiency criteria at the labeled 2.8 ng/mL threshold versus 54.0% at 5.1 ng/mL; the discordant patients had markedly higher body mass index (mean 37.7 versus 28.2 kg/m²), and every discordant patient in the low-likelihood group had a body mass index above 35 kg/m² (Yadav et al., Pituitary, 2026, 29(2):47).

Cardiac safety. A thorough QT study in 60 healthy adults at a supratherapeutic 2.0 mg/kg dose (four times the diagnostic dose) found a placebo-corrected QTcF increase of 9.6 ms with an upper confidence bound of 11.4 ms at 4 hours, and the preceding single-dose study saw a similar 10 to 11 ms prolongation at 0.5, 1.0, and 2.0 mg/kg with no clear dose dependence (Lissy et al., Clinical Pharmacology in Drug Development, 2021, 10(5):494–501; Klaus et al., Growth Hormone & IGF Research, 2020, 52:101321). The label states that the mechanism of the prolongation is unknown.

Pediatric program: a failed Phase 3. An open-label dose-escalation study in 24 children aged 2 to under 18 with suspected growth hormone deficiency tested 0.25, 0.5, and 1.0 mg/kg, reported no drug-related adverse events, and selected the top dose for a pivotal trial (Csákváry et al., Hormone Research in Paediatrics, 2021, 94(7-8):239–250). The pivotal DETECT trial (NCT04786873) enrolled 101 to 102 children aged 3 to 17 at sites in Europe, the United States and the Caucasus and compared macimorelin with arginine and clonidine stimulation tests, with deficiency status adjudicated by an independent panel; it completed on June 13, 2024 and, as announced in August 2024, did not meet its primary endpoint. The sponsor attributed the result to false positives on the comparator tests and to an exploratory optimal growth hormone cut point of 25.59 ng/mL, far above the 7 to 10 ng/mL conventionally used in children; a subsequent Type C meeting with the FDA did not open a path to pediatric approval on a post hoc analysis. The FDA’s position is now written into the label: an efficacy supplement approved July 23, 2026 added to Section 8.4 that diagnostic accuracy was not demonstrated in a multicenter, open-label, randomized crossover study of 102 pediatric patients aged 3 to 17 years and that safety and effectiveness in children have not been established. No results had been posted to the registry by November 3, 2026.

Therapeutic exploration. The only interventional therapeutic trial on record is a one-week pilot in 15 patients with cancer cachexia (NCT01614990), randomized to 0.5 or 1.0 mg/kg daily or placebo; none of the prespecified efficacy criteria were met, and no related adverse events were reported (Herodes et al., Journal of Cachexia, Sarcopenia and Muscle, 2023, 14(2):835–846). Mouse work has tested macimorelin for seizure suppression and disease modification in a pharmacoresistant epilepsy model through the ghrelin receptor, finding fewer and shorter seizures during treatment but no disease-modifying effect (Buckinx et al., European Journal of Neurology, 2021, 28(9):3100–3112), and that line has not advanced to a human trial. There is no registered trial of macimorelin for body composition, performance, or aging.

Commercial status. Aeterna Zentaris licensed US and Canadian rights to Strongbridge Biopharma on January 16, 2018; Novo Nordisk acquired the rights-holding entity on December 19, 2018, announced on August 29, 2022 that it was terminating the license, and the rights reverted to Aeterna after a 270-day notice period on May 23, 2023, the same day US sales were temporarily discontinued pending a new partner. Drugs@FDA lists Macrilen’s US marketing status as discontinued. After DETECT failed and the Type C meeting closed off a near-term pediatric indication, the parent company (renamed COSCIENS Biopharma after a 2024 merger) announced on March 5, 2026 that it would stop funding Aeterna Zentaris GmbH; the German subsidiaries filed for insolvency on March 23, 2026, COSCIENS ceased to control them on March 27, 2026 once a preliminary administrator was appointed, and the company said it expected to surrender its rights to Macrilen. The July 2026 US label names Novo Nordisk as the adverse-reaction contact while Drugs@FDA continues to list Aeterna Zentaris as the applicant. Ghryvelin remains authorized in the EU under a different marketing authorization holder, Atnahs Pharma Netherlands B.V. Whether the US product returns to the market depends on what the insolvency process does with the NDA.

Common dosage forms

• Approved product — Macrilen is supplied as white to off-white granules for oral solution in a single aluminum pouch containing 60 mg of macimorelin (as 68 mg of the acetate), packaged one pouch per box and stored refrigerated. The EU product, Ghryvelin, uses the same 60 mg pouch.
• No therapeutic or take-home format — there is no tablet, capsule, pen, or injectable presentation; the product exists only as a single-test diagnostic kit.
• Research supply — macimorelin has little presence in the research-peptide channel. Where it is listed at all, it is as a research-grade chemical reagent from laboratory suppliers rather than as a lyophilized vial product, and it would be unusual to see it alongside the injectable secretagogues.

Key considerations

• It is a peptidomimetic, not a peptide, and a diagnostic, not a treatment. The gem-diamino pseudo-tripeptide structure is what makes it orally active, and that oral activity has been used for exactly one purpose: provoking a single growth hormone peak to measure. Its data say nothing about chronic use, and the one therapeutic trial, in cancer cachexia, showed no efficacy signal over a week.
• Regulatory status. The FDA Approved status reflects the December 20, 2017 approval of Macrilen under NDA 205598, which remains in force. The product’s US marketing status is listed as discontinued, and its sponsor’s German operating company filed for insolvency on March 23, 2026, so the label is current while the supply is not.
• QT prolongation is the labeled safety signal. The roughly 10 ms QTcF increase has no known mechanism, and the label directs that drugs known to prolong the QT interval be avoided around the test.
• Test interpretation has unsettled edges. The labeled 2.8 ng/mL cut point and the 5.1 ng/mL threshold that performed best in the published analyses can classify the same patient differently, particularly at higher body mass index. The label notes that performance has not been established above a body mass index of 40 kg/m², that strong CYP3A4 inducers can produce false positives, and that recent-onset hypothalamic disease can produce false negatives.
• The pediatric indication failed. The Phase 3 trial did not demonstrate diagnostic accuracy, and the label now says so. Any description of macimorelin as a validated pediatric test is out of date.