Rhythm Pharmaceuticals’ setmelanotide promotes weight loss not only in adults, but also in children and adolescents with POMC deficiency and LEPR deficiency, two rare genetic obesity disorders, according to updated data from two Phase 3 clinical trials.
“We are encouraged to see therapeutic activity in children and adolescents,” Murray Stewart, MD, Rhythm’s chief medical officer, said in a press release.
“These chronic disorders often arise in childhood, with patients suffering from severe obesity and insatiable hunger beginning at a very young age. By intervening earlier, we believe it may be possible to reduce body weight and hunger significantly, thereby preventing the development of debilitating comorbidities often associated with early-onset, rapid weight gain and improving quality of life for patients and their families,” Stewart said.
He also said that data from an extension study showed that setmelanotide was well-tolerated for up to three years, with patients “continuing to maintain, or even deepen, their weight loss.”
These newly announced findings, along with previous top-line and additional data from two Phase 3 trials, were included in Rhythm’s filing of a marketing authorization application to the European Medicines Agency (EMA), seeking setmelanotide’s approval for treating people with POMC and LEPR deficiencies.
Stewart added that this submission is “another step toward our goal of delivering setmelanotide to patients with these ultra-rare disorders.” A similar application was submitted to the U.S. Food and Drug Administration (FDA) in March, with a decision expected on or before Nov. 27.
Dependent on setmelanotide’s approval, this designation allows Rhythm to qualify for a voucher redeemable for priority review of a new drug application for a different product. The voucher program seeks to boost treatment development for rare pediatric diseases that might not be profitable otherwise.
“We believe that receipt of the rare pediatric disease designation for setmelanotide, for which we have previously received breakthrough therapy and orphan drug status, underscores the FDA’s recognition of setmelanotide’s potential to treat POMC and LEPR deficiency obesities,” Stewart said in that press release.
The therapy also has received the EMA’s PRIority MEdicines and orphan designations for the treatment of genetic obesity disorders associated with an impaired MC4R pathway, which setmelanotide is intended to activate. These disorders include POMC and LEPR deficiencies, as well as Alström syndrome and Bardet-Biedl syndrome.
All such designations are meant to provide support and financial benefits to accelerate setmelanotide’s development. Also, they ensure marketing exclusivity for a period of time upon regulatory approval — seven years in the U.S. and 10 years in Europe.
Previous data from 20 POMC and LEPR deficiency patients enrolled in two Phase 3 trials — NCT02896192 for POMC deficiency and NCT03287960 for LEPR deficiency — showed that one year of setmelanotide treatment was safe and resulted in clinically meaningful reductions in patients’ weight and hunger levels. Setmelanotide was administered daily through an under-the-skin injection.
The new data concerned eight supplemental participants, including four children ages 6–12 — four with POMC deficiency and four with LEPR deficiency — and treated for one year with setmelanotide.
Results showed that all patients achieved the primary goal of 10% or greater weight loss, with a mean body weight reduction of 26.3% for POMC deficiency patients and 13.2% for LEPR deficiency patients. Data from evaluable patients also showed a mean 57.3% drop in hunger levels, consistent with results from the previous groups.
Combining the data from all trials’ participants, the team found that the primary goal of weight loss was achieved by 86% (12 of 14) of patients with POMC deficiency and by 60% (9 of 15) of those with LEPR deficiency.
Participants completing one year of treatment were given the option of joining a long-term extension study (NCT03651765), in which all patients will continue on setmelanotide.
As of April 16, data from the 15 patients — nine with POMC deficiency and six with LEPR deficiency — currently being followed showed that they successfully maintained durable weight loss and stable hunger levels for up to nearly three years.
Setmelanotide was generally safe and well-tolerated in the supplemental patient groups and in the extension study, consistent with the previously reported safety profile. The most common treatment-related side effects included injection site reactions, nausea and vomiting, and darkening of the skin.
Data from both the supplemental groups and the ongoing long-term extension study will continue to be analyzed. Rhythm plans to share more of these results at an upcoming medical meeting.
Top-line data from a Phase 3 trial (NCT03746522) evaluating setmelanotide’s safety and effectiveness in people with Bardet-Biedl syndrome and Alström syndrome also are expected by the first quarter of 2021.
Notably, the company expects to register a new weekly formulation of setmelanotide to regulatory agencies, since recent data from a Phase 2 clinical trial suggest that it may have comparable effectiveness to the current daily formulation.
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