FDA accepts setmelanotide NDA for obesity in patients down to 2 years

FDA accepts setmelanotide NDA for obesity in patients down to 2 years | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

Rhythm Pharmaceuticals has announced that the FDA has accepted a New Drug Application for setmelanotide (Imcivree) to treat obesity because of Bardet-Biedl syndrome (BBS) or pro-opiomelanocortin (POMC), including proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency obesity in children as young as 2 years old. The company stated in a press release a Prescription Drug User Fee Act date of December 26, 2024 has been set for potential FDA decision, and that setmelanotide has been granted Priority Review by the federal agency.

Setmelanotide is a melanocortin-4 receptor (MC4R) agonist that is currently indicated for adult and pediatric patients aged 6 years and older with monogenic or syndromic obesity due to POMC, PCSK1, or LEPR deficiency.

The supplemental New Drug Application was based on data from a multicenter, 1-year, open-label phase 3 trial among 12 patients aged between 2 years and younger than 6 years with obesity due to biallelic POMC/PCSK1 or LEPR deficiency or a clinical diagnosis of BBS. According to Rhythm's press release, setmelanotide treatment reached the primary endpoint with a 3.04 mean reduction in BMI-Z score and an 18.4% mean reduction in BMI.

"This milestone brings us another step closer to offering a precision therapy for young patients in the [United States] experiencing hyperphagia—a pathological hunger that leads to aberrant food-seeking behaviors—and severe obesity caused by rare MC4R pathway diseases,” said David Meeker, MD, who is the chairman, CEO, and president of Rhythm.

"[Setmelanotide] has been approved for more than [2] years and prescribed to hundreds of patients 6 years old and older, and we believe that treating patients at an even earlier age will positively affect the lives of these children and their families," Meeker said in the statement.

Last month, the European Commission expanded marketing authorization for setmelanotide to include children as young as 2 years of age with obesity because of BBS or POMC/PCSK1, or LEPR deficiency.

According to Rhythm, setmelanotide is not indicated for treatment in patients with the following conditions, as it is not expected to be effective:

• Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign.
• Other types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity.

The contraindication for setmelanotide is, "prior serious hypersensitivity to setmelanotide or any of the excipients in [setmelanotide]. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported," stated Rhythm in the press release.

The most common adverse reactions, with an incidence ≥20%, included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

Reference:

Rhythm Pharmaceuticals announces FDA acceptance for Priority Review of Supplemental New Drug Application for IMCIVREE® (setmelanotide) in Patients as Young as 2 years old. Rhythm Pharmaceuticals Inc. August 26, 2024. Accessed August 26, 2024. https://www.globenewswire.com/news-release/2024/08/26/2935458/0/en/Rhythm-Pharmaceuticals-Announces-FDA-Acceptance-for-Priority-Review-of-Supplemental-New-Drug-Application-for-IMCIVREE-setmelanotide-in-Patients-as-Young-as-2-years-old.html