Publications and Posters Related to MacrilenTM (macimorelin)

Publications and Posters

* Investigational product candidates. The safety and efficacy of RECORLEV (levoketoconazole) and veldoreotide have not been established.

Please see KEVEYIS Important Safety Information and Full Prescribing Information.
Please see Macrilen Important Safety Information and Full Prescribing Information.

About Macrilen

  • Macimorelin as a Diagnostic Test for Adult Growth Hormone Deficiency. Jose M. Garcia, Beverly M.K. Biller, Márta Korbonits, Vera Popovic, Anton Luger, Christian J. Strasburger, Philippe Chanson, Milica Medic-Stojanoska, Jochen Schopohl, Anna Zakrzewska, Sandra Pekic-Djurdjevic, Marek Bolanowski, Ronald Swedloff, Christina Wang, Thomas Blevins, Marco Marcelli, Nicola Ammer, Richard Sachse, Kevin C.J. Yuen. J Clin Endocrinol Metab. 2018 (online ahead of print). doi: 10.1210/jc.2018-00665.
    • Abstract:
      • Purpose: Diagnosis of adult growth hormone deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the gold standard GHST but is labor-intensive, may cause severe hypoglycemia, and is contraindicated in certain patients. Macimorelin, an orally-active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose.
      • Methods: This multicenter, open-label, randomized, 2-way crossover trial was designed to validate the efficacy and safety of a single-dose oral macimorelin for AGHD diagnosis compared to the ITT. Subjects with high (n=38), intermediate (n=37), and low (n=39) likelihood for AGHD and healthy, matched controls (n=25) were included in the efficacy analysis of the study.
      • Results: After the first test, 99% of macimorelin and 82% of ITTs were evaluable. Using GH cut-off levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for the ITT, negative agreement was 95.38% (CI 87%-99%), positive agreement was 74.32% (CI 63%-84%), sensitivity was 87%, and specificity was 96%. Upon retesting, reproducibility was 97% for macimorelin (n=33). In post-hoc analyses, a GH cut-off of 5.1 ng/mL for both tests resulted in 94% (CI 85-98%) negative agreement, 82% (CI 72-90%) positive agreement, 92% sensitivity and 96% specificity. No serious adverse events were reported for macimorelin.
      • Conclusions: Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with comparable accuracy to the ITT. A GH cut-off of 5.1 ng/mL for the macimorelin test provides excellent balance between sensitivity and specificity.
      To read more, click here. (A subscription to this site/publication is required to access the full article)
  • Validation of Macimorelin as a Diagnostic Test for Adult Growth Hormone Deficiency (AGHD): A Phase 3 Study in Comparison with the Insulin Tolerance Test (ITT). Jose M Garcia, Beverly MK Biller, Marta Korbonits, Vera Popovic-Brkic, Anton Luger, Christian J Strasburger, Philippe Chanson, Ronald S Swerdloff, Sandra Pekic-Djurdjevic, Thomas C Blevins, Marco Marcelli, Milica Medic-Stojanoska, Jochen Schopohl, Nicola Ammer, Richard Sachse and Kevin CJ Yuen. Poster LB SUN 59.
    • Abstract: The diagnosis of adult GH deficiency (AGHD) is challenging. Since GH is secreted in pulses, random measurements of GH levels will not reliably distinguish GH-deficient from GH-sufficient subjects. Accordingly, the diagnosis of AGHD often depends on GH stimulation tests (GHST) using agents known to provoke GH release above a certain level in healthy people to determine the maximum GH level in patients suspected of having the disorder. Currently, the insulin tolerance test (ITT) is considered the "gold" standard GHST and the glucagon stimulation test an reasonable alternative. Other GHSTs are either not available in the US or considered to have low accuracy. Macimorelin, a potent orally active GH secretagogue (GHS), could be used to assess for AGHD by measuring the stimulated GH levels after an oral dose of 0.5 mg/kg body weight. To read more, click here.
  • Pharmacokinetics and Pharmacodynamic Effects of an Oral Ghrelin Agonist in Healthy Subjects. Franziska Piccoli, Lukas Degen, Carol MacLean, Shajan Peter, Luisa Baselgia, Finn Larsen, Christoph Beglinger, and Jürgen Drewe. The Journal of Clinical Endocrinology & Metabolism. 92(5):1814–1820.
    EP01572 is the same as macimoreline
    • Abstract:
      • Context: An oral formulation of EP01572, a peptidomimetic growth hormone secretagogue, was studied. An oral delivery system would be preferable in many of the possible therapeutic indications of ghrelin agonists such as EP01572. Objectives: Our objective was to establish the pharmacological profile and the GH-releasing activity of increasing oral doses of EP01572 in healthy volunteers. In addition, the pharmacokinetics and pharmacological effects of EP01572 were investigated after intraduodenal (ID) administration.
      • Setting: This study was a single-center escalating dose study with oral and ID applications.
      • Subjects and Methods: In the first part, EP01572 was given orally to 36 male subjects; the treatment consisted of one oral dose of either EP01572 or placebo (0.005, 0.05, and 0.5 mg/kg body weight). Six subjects received two additional oral doses of EP01572: 0.125 and 0.25 mg/kg body weight. In the second part, the following treatments were performed in a randomized order: 1) administration of a bolus of saline (placebo) to the small intestine; 2) ID administration of a bolus of EP01572 at 0.2 mg/kg body weight; 3) ID perfusion of a bolus of EP01572 at 0.35 mg/kg body weight; and 4) ID perfusion of a bolus of EP01572 at 0.5 mg/kg body weight.
      • Results: The oral and ID administration of EP01572 induced a rapid and dose-dependent increase in plasma drug concentrations and a potent GH release in healthy male volunteers.
      • Conclusions: This study showed that EP01572 was active with regard to stimulation of GH release in humans after oral and ID administration. (J Clin Endocrinol Metab 92: 1814–1820, 2007)
      To read more, click here.

Current Management/Treatment Guidelines of Adult Growth Hormone Deficiency

  • Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline Mark E. Molitch, David R. Clemmons, Saul Malozowski, George R. Merriam, and Mary Lee Vance. J Clin Endocrinol Metab. June 2011, 96(6):1587–1609.
    • Abstract:
      • Objective: The aim was to update The Endocrine Society Clinical Practice Guideline on Evaluation and Treatment of Adult Growth Hormone Deficiency (GHD) previously published in 2006.
      • Consensus Process: Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes.
      • Conclusions: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks associated with GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual. (J Clin Endocrinol Metab 96: 1587–1609, 2011)
      To read more, click here.
    • Abstract:
      • Objective: The clinical features of adult GH deficiency (GHD) are nonspecific, and GH stimulation testing is often required to confirm the diagnosis. However, diagnosing adult GHD can be challenging due to the episodic and pulsatile GH secretion, concurrently modified by age, gender, and body mass index (BMI).
      • Methods: PubMed searches were conducted to identify published data since 2009 on GH stimulation tests used to diagnose adult GHD. Relevant articles in English language were identified and considered for inclusion in the present document.
      • Results: Testing for confirmation of adult GHD should only be considered if there is a high pretest probability, and the intent to treat if the diagnosis is confirmed. The insulin tolerance test (ITT) and glucagon stimulation test (GST) are the two main tests used in the United States. While the ITT has been accepted as the gold-standard test, its safety concerns hamper wider use. Previously, the GH–releasing hormone-arginine test, and more recently the GST, are accepted alternatives to the ITT. However, several recent studies have questioned the diagnostic accuracy of the GST when the GH cut-point of 3 mg/L is used and have suggested that a lower GH cut-point of 1 mg/L improved the sensitivity and specificity of this test in overweight/ obese patients and in those with glucose intolerance.
      • Conclusion: Until a potent, safe, and reliable test becomes available, the GST should remain as the alternative to the ITT in the United States. In order to reduce overdiagnosing adult GHD in overweight/obese patients with the GST, we propose utilizing a lower GH cut-point of 1 mg/L in these subjects. However, this lower GH cut-point still needs further evaluation for diagnostic accuracy in larger patient populations with varying BMIs and degrees of glucose tolerance. (Endocr Pract. 2016;22:1235-1244)
      To read more, click here.
  • Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for Pretreatment Endocrine Evaluation of Patients With Nonfunctioning Pituitary Adenomas. Maria Fleseriu, MD, Mary E. Bodach, MLIS, Luis M. Tumialan, MD, Vivien Bonert, MD, Nelson M. Oyesiku, MD, PhD, Chirag G. Patil, MD, Zachary Litvack, MD, Manish K. Aghi, MD, PhD, Gabriel Zada, MD. NEUROSURGERY VOLUME 79 | NUMBER 4 | OCTOBER 2016.
    • Abstract:
      • BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are among the most common pituitary lesions and may present with hypopituitarism and/or hyperprolactinemia.
      • OBJECTIVE: To review the existing literature as it pertains to preoperative endocrine assessment in the workup for NFPAs.
      • METHODS: A systematic review methodology was utilized to identify and screen articles assessing the role and results of preoperative laboratory assessment in patients with NFPAs. The prevalence of individual pituitary hormonal axis deficiencies was reviewed.
      • RESULTS: Twenty-nine studies met inclusion criteria for analysis. No class I evidence was available, and all studies met criteria for class II evidence. Baseline serum laboratory assessment showed a prevalence of overall hypopituitarism in 37% to 85% of patients. The most common hormonal axis deficiency was growth hormone deficiency, prevalent in 61% to 100% of patients. The next most common deficit was hypogonadism, seen in 36% to 95% of patients. Adrenal insufficiency was diagnosed in 17% to 62% of patients. Finally, hypothyroidism was seen in 8% to 81% of patients. Hyperprolactinemia was seen in 25% to 65% of patients, with a mean level of 39 ng/mL and with a minority of patients exceeding a serum prolactin level of 200 ng/mL. No evidence supporting routine biomarker testing (eg, a-subunit or chromogranin A) or genetic testing in patients with sporadic NFPAs was available.
      • CONCLUSION: Despite a paucity of class I evidence, multiple retrospective studies have demonstrated a high prevalence of hypopituitarism in patients with NFPAs. Routine endocrine analysis of all anterior pituitary axes to assess for hypopituitarism is recommended, with prolactin and insulin-like growth factor 1 evaluation also valuable to assess for hypersecretion states that might not be clinically suspected. The full guidelines document for this chapter can be located at pituitary-adenomas/Chapter_3.
      To read more, click here.
  • Hormonal Replacement in Hypopituitarism in Adults. Maria Fleseriu (chair), Ibrahim A. Hashim, Niki Karavitaki, Shlomo Melmed, M. Hassan Murad, Roberto Salvatori, and Mary H. Samuels. J Clin Endocrinol Metab. November 2016, 101(11):3888–3921.
    • Abstract:
      • Objective: To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults.
      • Participants: The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline.
      • Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.
      • Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines.
      • Conclusions: Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries. (J Clin Endocrinol Metab 101: 3888–3921, 2016)
      To read more, click here.

Growth Hormone Deficiency and Articles Related to Traumatic Brain Injury

  • Prevalence of Pituitary Hormone Dysfunction, Metabolic Syndrome, and Impaired Quality of Life in Retired Professional Football Players: A Prospective Study Daniel F. Kelly, Charlene Chaloner, Diana Evans, Amy Mathews, Pejman Cohan, Christina Wang, Ronald Swerdloff, Myung-Shin Sim, Jihey Lee, Mathew J. Wright, Claudia Kernan, Garni Barkhoudarian, Kevin C.J. Yuen, and Kevin Guskiewicz. JOURNAL OF NEUROTRAUMA. 31:1161–1171 (July 1, 2014).
    • Abstract: Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30–65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3 – 10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8 – 6.0), 28 (41.2%) were GHD using a peak GH cutoff of < 3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey ( p = 0.016) and trended toward lower scores on the SF-36 MCS ( p = 0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism ( p = 0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI. To read more, click here.
  • Neuroendocrine consequences of traumatic brain injury Munoz, Alejandro; Urban, Randall. NEUROENDOCRINOLOGY. August 2013 - Volume 20 - Issue 4 - p 354–358.
    • Abstract: Purpose of review This article attempts to summarize findings of recent publications addressing the prevalence, effects, and treatment of pituitary hormone deficiency following traumatic brain injury (TBI).
      Recent findings A number of recent studies of TBI victims offer larger samples and much longer follow-up times. However, the prevalence of pituitary hormone deficiency continues to vary widely, underscoring the influence of patient selection, differences in endocrine testing, and patient's comorbidities and age. Growth hormone deficiency (GHD) continues to be the most frequently detected type of pituitary dysfunction. Several reports show the influence of GHD on functional outcomes of TBI victims beyond what is predicted by trauma severity. Emerging data support the notion growth hormone (GH) replacement as a useful intervention to improve symptomatology and functional outcomes among adequately selected GH-deficient patients recovering from TBI.
      Summary Pituitary dysfunction is prevalent following TBI. Pituitary dysfunction seems to influence functional outcomes in some patients recovering from brain injury. Adequately selected patients could benefit from hormonal replacement. To read more, click here. (A subscription to this site/publication is required to access the full article)
  • American Association of Clinical Endocrinologiests and American College of Endocrinology Disease State Clinical Review. Nicholas A. Tritos, MD, DSc; Kevin C.J. Yuen, MD, FRCP (UK); Daniel F. Kelly, MD; on behalf of the AACE Neuroendocrine and Pituitary Scientific Committee. AACE/ACE Disease State Clinical Review.
    • Abstract:
      • Objective: Traumatic brain injury (TBI) is now recognized as a major public health concern in the United States and is associated with substantial morbidity and mortality in both children and adults. Several lines of evidence indicate that TBI-induced hypopituitarism is not infrequent in TBI survivors and may contribute to the burden of illness in this population. The goal of this article is to review the published data and propose an approach for the neuroendocrine evaluation and management of these patients.
      • Methods: To identify pertinent articles, electronic literature searches were conducted using the following keywords: “traumatic brain injury,” “pituitary,” “hypopituitarism,” “growth hormone deficiency,” “hypogonadism,” “hypoadrenalism,” and “hypothyroidism.” Relevant articles were identified and considered for inclusion in the present article.
      • Results: TBI-induced hypopituitarism appears to be more common in patients with severe TBI. However, patients with mild TBI or those with repeated, sports-, or blast-related TBI are also at risk for hypopituitarism. Deficiencies of growth hormone and gonadotropins appear to be most common and have been associated with increased morbidity in this population. A systematic approach is advised in order to establish the presence of pituitary hormone deficiencies and implement appropriate replacement therapies.
      • Conclusion: The presence of traumatic hypopituitarism should be considered during the acute phase as well as during the rehabilitation phase of patients with TBI. All patients with moderate to severe TBI require evaluation of pituitary function. In addition, symptomatic patients with mild TBI and impaired quality of life are at risk for hypopituitarism and should be offered neuroendocrine testing. (Endocr Pract. 2015;21:823-831)
      To read more, click here.
  • Growth hormone deficiency and hypopituitarism in adults after complicated mild traumatic brain injury. Stefania Giuliano, Serafina Talarico, Lucia Bruno, Francesco Beniamino Nicoletti, Claudio Ceccotti, Antonino Belfiore. Endocrine. (2017) 58:115–123.
    • Abstract:
      • Purpose: Traumatic brain injury is considered the main cause of hypopituitarism in adults, and GH deficiency appears to be the most frequent pituitary deficit. Most of the available studies have included all degrees of severity of trauma. We aimed to assess pituitary function and GH deficiency in adult patients at different time lengths after complicated mild TBI according to Glasgow Coma Scale. We also aimed to evaluate whether mild TBI patients with GH deficiency had developed alterations in the glycolipid profile.
      • Methods: Forty-eight patients (34 men and 14 women) with complicated mild TBI were included in the study. Twentythree patients were evaluated at 1 year (Group A) and 25 patients at 5 years or longer after the injury (Group B). All patients underwent basal hormonal evaluation for pituitary function. GH deficiency was investigated by the combined test (GH releasing hormone + arginine). The glycolipid profile was also evaluated.
      • Results: GH deficiency occurred in 8/23 patients (34.7 %) of Group A and in 12/25 patients (48 %) of Group B. In addition, two patients, one in each group, showed evidence of central hypothyroidism. Patients with GH deficiency, especially in Group A, presented a higher frequency of visceral adiposity and adverse metabolic profile as compared to no-GH deficiency patients.
      • Conclusions Patients examined at 1 year or several years from complicated mild TBI had a similarly high occurrence of isolated GH deficiency, which was associated with visceral adiposity and metabolic alterations. Our findings suggest that patients undergone complicated mild TBI should be evaluated for GH deficiency even after several years from trauma.
      To read more, click here.

Important Safety Information for Macrilen

What is Macrilen?

Macrilen (pronounced ma-kri-len) (macimorelin) is a prescription oral solution that is used to test for adult growth hormone deficiency (AGHD).

What should you know about Macrilen?

  • Taking Macrilen with certain other medications may cause irregular changes to your heart rhythm. Before taking Macrilen, tell your healthcare provider about all your medications, as you may need to temporarily stop taking some medications before you take Macrilen.
  • Some medications may cause a false positive result when taken with Macrilen. Before taking Macrilen, tell your healthcare provider about all the medications you take, including growth hormone.
  • Tell your healthcare provider if you were recently diagnosed with hypothalamic disease, as this can cause a false negative result with Macrilen.
  • You will need to fast (go without food) for at least 8 hours before taking Macrilen.

What are the most common side effects with Macrilen?

The most common side effects were changed sense of taste, dizziness, headache, fatigue, nausea, hunger, diarrhea, upper respiratory tract infection, feeling hot, excessive sweating, sore nose and throat, and decreased heart rate.

These are not all of the possible side effects of Macrilen. Call your healthcare provider for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088.

Please see Macrilen Important Safety Information and Full Prescribing Information.

© 2018 Strongbridge Biopharma plc
STRONGBRIDGE BIOPHARMA® is a registered trademark of the Strongbridge Biopharma plc. companies, which include Strongbridge Ireland Limited and Strongbridge U.S. Inc.
KEVEYIS® is a registered trademark licensed exclusively in the U.S. to Strongbridge Biopharma plc.
Macrilen is a trademark of Aeterna Zentaris GmbH, licensed exclusively in the U.S. and Canada to Strongbridge Ireland Limited.
MLR-0010 V13 01/2018

900 Northbrook Drive, Suite 200
Trevose, PA 19053
United States
Phone: +1 610-254-9200
[email protected]

Privacy Statement
Compliance Program