Bivamelagon
Bivamelagon (LB54640), oral melanocortin-4 receptor agonist
Written by Aaron CuhaReviewed Sep 2026
Also known as: LB54640, LB-54640
An oral MC4R agonist being developed as a tablet counterpart to injected setmelanotide. A 28 person phase 2 in hypothalamic obesity completed in February 2026 with no results posted, and there is no peer reviewed publication on the compound at all.
Overview
Bivamelagon is an oral agonist of the melanocortin-4 receptor, the same receptor that setmelanotide activates by daily injection. It was discovered by LG Chem under the code LB54640 and licensed to Rhythm Pharmaceuticals, which is developing it for hypothalamic obesity, the weight gain that follows damage to the hypothalamus from tumours or their treatment. The point of the programme is convenience: an MC4R drug you can swallow rather than inject.
What has been measured in people is, so far, unpublished. A first in human phase 1 in 112 healthy adults with overweight or obesity (NCT06040372, LG Chem) completed in 2022. A phase 2 in 28 people with hypothalamic obesity (NCT06046443, Rhythm) completed in February 2026 with no results posted on the registry as of September 2026. An open label extension (NCT07156578) is enrolling by invitation with a projected completion in 2028, and a four person phase 2 in genetic obesity (NCT06041841) is listed with an unknown status. A PubMed search for bivamelagon or LB54640 returns zero records. Any weight loss figure in circulation comes from company presentations and cannot be checked against a paper or a registry result.
In animals, the class background is real but is not about this molecule. A 2026 Nature Communications paper in male primates with diet induced obesity showed that a dual MC3R and MC4R agonist produced weight loss, and argued that selective MC4R agonism alone has had limited success in general obesity. Bivamelagon is not approved anywhere and no regulator has reviewed it.
Mechanism of action
In human pharmacology of the class, MC4R activation in the hypothalamus reduces appetite; this is the pathway that loss of function mutations in POMC, PCSK1 and LEPR disrupt upstream of the receptor, and that setmelanotide restores. Bivamelagon is described by its developer as a selective MC4R agonist that is orally bioavailable. No receptor pharmacology, pharmacokinetics or dose response for bivamelagon has been published in a peer reviewed journal, so the mechanism on this page is inferred from the class and from the sponsor's description, not from data on the compound. In primates, a 2026 study of a different oral dual MC3R and MC4R agonist found that adding MC3R activation produced greater weight loss than MC4R agonism alone. That is a finding about the receptor system in monkeys, not about bivamelagon.
Human evidence
Bivamelagon has been given to at least 140 people across a phase 1 and a phase 2, and nothing from either has been published or posted. There is no peer reviewed human data on this compound.
- NCT06040372: 112 healthy adults with overweight or obesity, phase 1, LG Chem, completed March 2022. No results posted, no publication.
- NCT06046443: 28 people with hypothalamic obesity, phase 2, Rhythm Pharmaceuticals, completed 9 February 2026. No results posted as of September 2026.
- NCT07156578: open label extension in hypothalamic obesity, estimated 25 participants, enrolling by invitation, projected completion April 2028.
- NCT06041841: phase 2 in genetic obesity, estimated 4 participants, status unknown.
- PubMed search for bivamelagon or LB54640, September 2026: zero records.
What this does not tell you: Nothing on this page can tell you whether bivamelagon lowers weight, by how much, in whom, or at what cost in side effects, because none of that has been reported outside company materials. The indication being studied, hypothalamic obesity, is rare and mechanistically distinct from common obesity, so even a positive result there would not transfer to general weight loss. Setmelanotide, the injected MC4R agonist in the same family, commonly causes skin darkening and injection site reactions; whether an oral MC4R agonist shares the pigmentation effect is unknown.
Reading the research record
This is a normal early stage pharmaceutical programme and the record looks the way early programmes look: registry entries, a completed phase 2 whose results belong to the sponsor until they choose to publish or present them, and no independent data. Rhythm has a commercial reason to develop an oral MC4R agonist, since setmelanotide is its approved injected product for the same receptor and the same rare obesity indications, and a tablet would extend that franchise. That interest cuts both ways: the sponsor will run the trials, and the sponsor controls when and how the results appear.
The reason bivamelagon shows up in peptide catalogues is the receptor, not the molecule. Setmelanotide, bremelanotide and the melanotans are peptides; bivamelagon is an orally available agonist at the same receptor and is sold alongside them by association. There is no legitimate supply of it outside the trials, and anything offered under the name cannot be checked against a published specification, because none exists.
The evidence, charted
Fig. 1 · evidence composition
4of 5 citations (80%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2020 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2024
A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity (NCT06046443)
Phase 2, 28 participants with hypothalamic obesity, started July 2024, primary completion 9 February 2026. Status completed; no results posted as of September 2026. Sponsor funded.
ClinicalTrials.gov, Rhythm Pharmaceuticals - Human2025
A Long-Term Study of Bivamelagon in Participants With Hypothalamic Obesity (NCT07156578)
Open label extension, phase 2, estimated 25 participants, enrolling by invitation since November 2025 with primary completion projected for April 2028. Sponsor funded.
ClinicalTrials.gov, Rhythm Pharmaceuticals - Human2020
A First in Human Study to Assess the Safety, Tolerability of LB54640 in Healthy Overweight and Obese Subjects (NCT06040372)
Phase 1, 112 healthy adults with overweight or obesity, run by LG Chem from March 2020 to March 2022. Completed; no results posted and no publication located.
ClinicalTrials.gov, LG Chem - Human2023
A Phase 2 Study to Assess Efficacy and Safety of LB54640 in Patients With Genetic Obesity (NCT06041841)
Estimated 4 participants with genetic obesity; the record has not been updated and is listed with an unknown status.
ClinicalTrials.gov, LG Chem - Animal2026
Dual activation of MC3R and MC4R drives weight loss and reduces food intake in male primates with obesity
Class background only, not about bivamelagon. In male nonhuman primates with diet induced obesity, an oral dual MC3R and MC4R agonist (710GO) produced weight loss, and the authors note that selective MC4R agonists have had limited clinical success in general obesity. The senior author holds equity in the company developing the compound.
Nature Communications
Frequently asked questions
Has bivamelagon produced weight loss in a trial?
A 28 person phase 2 in hypothalamic obesity completed in February 2026, so the trial has been run. Its results have not been posted on the registry or published in a journal as of September 2026. Any percentage you see attributed to it comes from company presentations and cannot be independently checked.
How is it different from setmelanotide?
Both activate the melanocortin-4 receptor. Setmelanotide is a cyclic peptide given by daily injection and is approved for obesity caused by specific genetic defects and for Bardet-Biedl syndrome. Bivamelagon is an orally available agonist at the same receptor. Whether it matches setmelanotide's effect, or shares its skin darkening side effect, has not been reported.
Is bivamelagon a peptide?
Its developer describes it as an oral MC4R agonist and no structure has been published in a peer reviewed journal. It appears in peptide catalogues because of its receptor, which the peptide drugs setmelanotide and bremelanotide also target.
Can I buy bivamelagon?
It is an investigational compound with no approval in any country and no published specification. Products sold under the name cannot be verified against anything.