By Ben Adams
Boston’s Rhythm has produced highly impressive results for its FDA “breakthrough” candidate setmelanotide in people with an ultra-rare genetic disease that causes early onset obesity due to insatiable hunger.
The condition, known as pro-opiomelanocortin (POMC) deficiency obesity, is incredibly rare with only around 500 people worldwide at most believed to have the disease.
It’s a condition that causes a huge, unrelenting desire to eat (known as hyperphagia) from a very young age, causing patients to put on a lot of weight from childhood--and the resultant health issues that this comes with.
The results of the open label Phase II trial were posted in the NEJM and although in just 2 patients (only 50 patients are currently documented to have the condition), the data have made a major impact on their lives.
The biotech notes that both patients enrolled in the study (who are still being treated with the drug) had extreme, early-onset obesity and severe hyperphagia, along with elevated insulin levels.
The first patient was 21 years old with a compound heterozygous loss of function POMC gene mutation, while the second was slightly older at 26 with a homozygous POMC mutation.
The first patient lost a staggering 112.4 lbs over 42 weeks, from a baseline weight of 341.7 lbs, while the second lost 45.2 lbs over 12 weeks, from a baseline weight of 336.9 lbs.
This came as a result of a steady and sustained weight loss in both patients that averaged between 3.75 to 4.4 lbs per week with the setmelanotide injection. This loss was the company said mainly due to loss of body fat.
On top of this, the pre-study elevated insulin levels went down substantially (though data were not shared).
Crucially, both patients also saw substantial reductions in hunger--with hunger scores from baseline of 9-10 (using a Likert score 0-10; 0 being no hunger and 10 being extreme hunger) to 0-1, essentially reversing their hyperphagia.
"These results provide further validation of the critical role of the MC4 pathway in weight regulation and the potential for setmelanotide to restore lost activity in this pathway by bypassing upstream defects of MC4R and by activating the MC4 pathway below such defects, said Peter Kühnen, Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin, Germany, lead investigator in the trial and lead author of the publication.
“In this way, setmelanotide may serve as replacement therapy to re-establish weight and appetite control in patients with POMC deficiency and potentially other genetic disorders associated with obesity.”
Its lead, first-in-class drug is a melanocortin 4 receptor (MC4R) agonist and is believed to work on this MC4 pathway, a key component that regulates energy expenditure, homeostasis, and appetite.
Keith Gottesdiener, CEO of Rhythm, added: “By targeting replacement therapy for the treatment of MC4 pathway deficiencies, setmelanotide represents a new and highly promising approach to the treatment of obesity associated with POMC deficiency and potentially other genetic disorders.
“We look forward to advancing the development program for setmelanotide and are grateful to our investigators and the participants in our clinical trial for their dedication and commitment to this important research effort.”
Setmelanotide is also undergoing separate trials for the treatment of Prader-Willi syndrome (PWS)--a rare genetic disorder that also causes unrelenting hyperphagia and life-threatening obesity.