MK-677 Has Not Been Abandoned

On the Discord channel recently, there has been some conjecture on MK-677 and if it is still actively being researched and trialed on humans. This first seemed to surface about a week ago, and it’s been repeated and speculated on casually by several including myself. Essentially, it was rumored that a phase 2 trial was abandoned due to cardiac enlargement and/or cardiac failure and the MK-677 was toast.

Fortunately, while rooted in some truth, it’s not quite that bad:

Longer-term studies with ibutamoren are available, and of these, only one observed significant AEs related to ibutamoren use. Adunsky et al examined the role of ibutamoren in recovery from hip fracture in 123 elderly patients during 24 weeks of treatment, and this was the only randomized double-blinded, placebo-controlled trial that was stopped early because of concerns that ibutamoren might increase the rate of congestive heart failure. Four patients in the ibutamoren group (6.5%) and one in the placebo group (1.7%) developed congestive heart failure during the study, although the higher congestive heart failure rate in the ibutamoren group might have been due in part to higher baseline blood pressures in that group.More generally, more AEs were reported in patients on ibutamoren than in those on placebo (48 [77%] vs 33 [55%], respectively) in this study.https://www.smr.jsexmed.org/article/S2050-0521(17)30032-X/pdf

The study itself was stopped, and as far as I can tell, MK677 is still very much being actively investigated, with multiple studies being released in 2018. The results of this group are far from conclusive given the nature of the subjects i.e. old and sedentary. Here’s the study abstract, and just two years later a study with a similar age group and a larger sample showed no such effects.

Human growth hormone at physiological levels is certainly linked to enlarged organs (RIP Rich), but given that this finding has not been replicated in the multiple studies since I think we’re OK here. We can put this broscience to bed.


Edit 12/12/18, courtesy of /u/stolenlunches for this text

Published: Sep 24, 2018 AUSTIN, Texas--(BUSINESS WIRE)-- Lumos Pharma, Inc., a clinical stage biopharmaceutical company focused on development and commercialization of therapeutics for rare and neglected diseases, today announced that it has acquired the license for LUM-201, an investigational orally administered small molecule that promotes secretion of growth hormone from the pituitary gland, from Ammonett Pharma LLC. Lumos plans to initiate a Phase IIb trial in 2019 in patients with Pediatric Growth Hormone Deficiency (PGHD) to compare multiple doses of LUM-201 to daily injections of recombinant human growth hormone, which is the current standard of care. https://www.biospace.com/article/releases/lumos-pharma-acquires-candidate-for-oral-treatment-of-growth-hormone-deficiency/. Note that LUM-201 is an oral form of MK677

Further reading:

  1. https://globenewswire.com/news-release/2017/05/23/995095/0/en/Ammonett-Pharma-Receives-Positive-Opinion-from-European-Orphan-Medicinal-Products-Committee-for-MK-0677-for-Treatment-of-Pediatric-Growth-Hormone-Deficiency.html
  2. https://globenewswire.com/news-release/2017/05/25/996045/0/en/Ammonett-Pharma-Receives-Notice-of-Allowance-of-U-S-Patent-for-Oratrope-Related-to-Detecting-and-Treating-Growth-Hormone-Deficiency.html
  3. https://clinicaltrials.gov/ct2/show/NCT00116129https://clinicaltrials.gov/ct2/show/NCT00474279
  4. https://adisinsight.springer.com/drugs/800007434
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41459/https://www.ncbi.nlm.nih.gov/pubmed/8940347https://www.ncbi.nlm.nih.gov/pubmed/28340044