Macimorelin

Macimorelin acts as an agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a), also known as the ghrelin receptor, located on somatotroph cells of the anterior pituitary. Upon oral administration and absorption, it binds GHS-R1a and stimulates growth hormone release through a pathway independent of GHRH. The GH response is measured to determine whether pituitary GH secretory capacity is intact or deficient. Peak GH levels below established cut-off values confirm AGHD diagnosis.

Macimorelin has fully established, FDA-approved dosing, but it is a single-use oral diagnostic: 0.5 mg/kg once, taken as a reconstituted oral solution after an 8-hour fast, to provoke GH release for diagnosing adult growth hormone deficiency. It has no repeated, ongoing or cycled therapeutic dosing of any kind.

No light-sensitivity or freeze-thaw statement appears in the Macrilen prescribing information; those fields are left null rather than guessed. Reconstitution must be performed by a healthcare professional per the label.

• Garcia JM, Swerdloff R, Wang C, Kyle M, Kipnes M, Biller BM, Cook D, Yuen KC, Bonert V, Dobs A, Molitch ME, Merriam GR (2013) Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency ↗
  The Journal of Clinical Endocrinology and MetabolismPMID 23559086DOI

  Multicentre open-label validation in 50 adults with GH deficiency and 48 controls; peak GH after oral macimorelin was 2.36 +/- 5.69 ng/mL in patients versus 17.71 +/- 19.11 ng/mL in controls (p<0.0001).

• Garcia JM, Biller BMK, Korbonits M, Popovic V, Luger A, Strasburger CJ, Chanson P, Medic-Stojanoska M, Schopohl J, Zakrzewska A, Pekic S, Bolanowski M, Swerdloff R, Wang C, Blevins T, Marcelli M, Ammer N, Sachse R, Yuen KCJ (2018) Macimorelin as a Diagnostic Test for Adult GH Deficiency ↗
  The Journal of Clinical Endocrinology and MetabolismPMID 29860473DOI

  Pivotal multicentre randomised two-way crossover trial versus the insulin tolerance test: at GH cutoffs of 2.8 ng/mL (macimorelin) and 5.1 ng/mL (ITT), negative agreement was 95.38%, positive agreement 74.32%, sensitivity 87%; 99% of macimorelin tests were evaluable versus 82% of ITTs.

• Csakvary V, Erhardt E, Vamosi I, Toke J, Boros AG, Jasik B, Ammer N, Sachse R, Bidlingmaier M (2021) Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macimorelin in Children with Suspected Growth Hormone Deficiency: An Open-Label, Group Comparison, Dose-Escalation Trial ↗
  Hormone Research in PaediatricsPMID 34438400DOI

  First paediatric study (EudraCT 2018-001988-23): 24 children received ascending single oral doses of macimorelin at 0.25, 0.5 and 1.0 mg/kg, with safety, tolerability and PK/PD endpoints.