MHRA Expands Imcivree Authorization for Acquired Hypothalamic Obesity in UK

MHRA expands Imcivree authorization for acquired hypothalamic obesity in UK

Rare Daily Staff

Rhythm Pharmaceuticals said the UK Medicines and Healthcare products Regulatory Agency has expanded the authorization for Imcivree to include adults and children ages 4 and older living with acquired hypothalamic obesity caused by injury to or impairment of the hypothalamus.

Acquired hypothalamic obesity is a rare condition that can develop after a tumor affects the hypothalamic region of the brain, after treatment for such a tumor, or following traumatic brain injury, stroke, inflammation, or certain anatomical differences. It can lead to ongoing, intense hunger, lower energy use by the body, and rapid, persistent weight gain.

Imcivree is designed to activate the melanocortin-4 receptor, or MC4R, pathway, which helps regulate hunger, energy balance and body weight. In acquired hypothalamic obesity, damage or dysfunction in the hypothalamus may reduce alpha-melanocyte-stimulating hormone production and disrupt signaling through that pathway, contributing to persistent hunger, reduced energy expenditure and rapid, sustained weight gain.

The decision means eligible patients in the United Kingdom now have an approved treatment option intended to help address both obesity and hunger associated with the condition. However, regulatory authorization does not automatically mean the treatment will be routinely available through the National Health Service (NHS). Rhythm said it will work with the NHS on coverage guidance for Imcivree in acquired hypothalamic obesity.

Imcivree, also known as setmelanotide, works by activating the melanocortin-4 receptor, or MC4R, pathway. This pathway helps regulate hunger, energy balance, and body weight. In acquired hypothalamic obesity, hypothalamic damage can interfere with signaling through this pathway, contributing to the physical symptoms many patients experience.

The MHRA also granted Imcivree orphan-drug designation for acquired hypothalamic obesity, Rhythm said. Orphan-drug designation is intended to support the development of treatments for rare diseases.

“This authorization marks an important milestone for patients in the UK living with acquired HO,” said David Meeker, Rhythm’s president and CEO. “Healthcare providers now have an approved treatment option for eligible patients that addresses the underlying biology of this disease.”

The authorization was supported by results from Rhythm’s phase 2 study and its phase 3 TRANSCEND trial. In the study, participants who received Imcivree had a mean 16.5 percent reduction in body mass index (BMI) from baseline after 52 weeks, while the placebo group had a mean 3.3 percent increase in BMI, according to the company. Participants treated with Imcivree also reported reductions in hunger.

The trial results were published in The New England Journal of Medicine. The most commonly reported treatment-emergent side effects included nausea, vomiting, diarrhea, injection-site reactions, skin darkening, and headache.pubmed.ncbi.nlm.nih

Sadaf Farooqi of the University of Cambridge said the findings support a targeted treatment approach for a community that previously had no approved therapy in the UK.

“Acquired hypothalamic obesity is a complex condition that can have profound effects on the quality of life and long-term health of children and adults with brain tumors affecting the hypothalamus,” Farooqi said.

Imcivree was already authorized in the UK for certain rare genetic forms of obesity, including Bardet–Biedl syndrome and obesity linked to confirmed POMC, PCSK1, or LEPR deficiencies. The expanded authorization specifically applies to acquired hypothalamic obesity in patients ages 4 and older.

Photo: David Meeker, Rhythm’s president and CEO