Rare pediatric disease designation has just been granted to Rhythm Pharmaceuticals for their investigative therapy called setmelanotide. This drug is being investigated as a therapeutic option for two conditions- leptin receptor deficiency obesity (LEPR) and pro-opiomelanocortin deficiency obesity (POMC). Neither of these ultra-rare diseases have an approved treatment currently.
Setmelanoitde
Setmelanotide is a melanocortin-4 receptor agonist (MC4R). It has already been given Breakthrough Therapy Designation by the FDA and PRIME designation by the EMA. Both organizations have also granted Orphan Drug status.
Rhythm submitted a New Drug Application to the FDA, and the FDA has provided Priority Review for the application.
MC4R is a part of the pathway that regulates appetite and energy expenditure. Patients diagnosed with LEPR or POMC obesity have an impaired MC4R pathway. A therapy which targets the repair of this pathway could reduce patient’s hunger cues, and ultimately their weight.
LEPR and POMC Deficiency Obesities
LEPR and POMC are caused by mutations in the LEPR and POSK1 or POMC genes respectively. It is believed that both of these conditions are under diagnosed but both are rare. The conditions cause insatiable hunger, obesity from childhood on, endocrine abnormalities, and other symptoms. Patients with POMC may have a lighter skin pigmentation and red hair. Lifestyle changes including diet and exercise are unable to combat the symptoms either group of patients experience.
The symptoms progress over time and become more debilitating.
Rhythm is hopeful that setmelanotide will become the first approved therapy for these conditions which can be administered in early childhood and halt symptoms before they become so severe.
To learn more about LEPR deficiency obesity, click here.
To learn more about POMC deficiency obesity, click here.
Clinical Trials
Last August (2019), positive results from two Phase 3 studies were announced. Primary and secondary endpoints were all met. Patients experienced decreased hunger and significant weight loss.
Then, just last month (June 2020), new data was announced, further supporting this therapy. 8 more patients had received the medication. 4 of these were children between the ages of 6 and 13. All patients, regardless of LEPR or POMC diagnosis, achieved the established primary endpoint. This was at least a 10% weight loss after 52 weeks of being on the therapy.
You can read more about this therapy here.
