Today, Boston-based Rhythm Pharmaceuticals Inc. announced that its long-term data on Phase 2 clinical trials of its advanced drug candidate setmelanotide was published in the journal Nature Medicine. Rhythm is a company that develops and promotes therapies for rare hereditary obesity. Biopharmaceutical company.
The clinical phase 2 trial data released this time comes from three leptin receptor (LEPR)-deficient obesity patients, which affect approximately 2,000 people in the US. These patients have no control over eating desire (gluttony), and With a serious weight gain.
Setmelanotide is a first-in-class oligopeptide melanocortin-4 receptor (MC4R) agonist, which was previously approved by the FDA for its breakthrough therapy. In recent years, the MC4R gene has become an obesity field. Research hotspots. Epidemiological studies have found that the MC4R gene mutation is 1.0-2.5% in people with a body mass index (BMI) greater than 30, which is the most common genetic defect that causes obesity. In addition, multiple evidences are also available. It is indicated that it is associated with insulin resistance and drug-induced obesity.
Long-term data from this open-label clinical trial showed that daily subcutaneous injection of setmelanotide reduced excessive diet and body weight in three patients with LEPR-deficient obesity. One subject lost 21% in 26 weeks and was There was no weight rebound in the next 35 weeks; another subject not only lost a lot of weight, but the appetite index of 10 points was reduced from 9.5 to 2! Setmelanotide was well tolerated with no serious adverse events. Report. This is a key finding because early MC4R agonists have significant side effects, including elevated blood pressure and heart rate.
In addition, the researchers performed a series of in vitro analyses of MC4R function, and the data showed:
The mechanism by which setmelanotide activates MC4R may differ from natural ligands and first-generation synthetic agonists;
Setmelanotide may act by antagonizing naturally occurring neurotransmitters that inhibit MC4R activation;
Setmelanotide activates a specific MC4R mutation that is not activated by the natural ligand MSH (melanocyte hormone), which may make it useful in the treatment of other types of obesity.
Rhythm is currently recruiting patients in its key phase 3 clinical trials to assess the role of setmelanotide in LEPR-deficient obesity.
Dr. Keith Gottesdiener, CEO of Rhythm, said: 'We are pleased to announce the long-term results of Phase 2 clinical studies in the peer review journal Nature Medicine, whether it is for our clinical development projects or for currently no approved treatments. The program's rare hereditary obesity is an important milestone. We are also encouraged to continue our efforts to improve our understanding of the cellular and molecular mechanisms of the MC4 pathway. In vitro data suggest that setmelanotide may save Specific MC4R mutations, natural ligands may not work for such patients, but may benefit from setmelanotide treatment, a fact worthy of further study.
We look forward to in-depth research on the drug to bring more useful data, to bring positive effects to patients suffering from obesity.
