“Many patients and families who live with these diseases face an often burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, M.D., pediatric endocrinologist at the University of Florida Health. “This FDA approval marks an important turning point, providing a much-needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity.”
“We know that not all obesity is the same, and genetic testing plays a key role in enabling physicians, patients and families to understand the underlying cause of certain severe obesities,” said Murray Stewart, M.D., Chief Medical Officer of Rhythm. “In addition to POMC, PCSK1 and LEPR genes, we are continuing our efforts to identify further genes and populations to evaluate the potential for setmelanotide to address the insatiable hunger and early-onset severe obesity that characterize these diseases.”
Imcivree is not approved for obesity due to suspected POMC, PCSK1, or LEPR deficiency with variants classified as benign (not causing disease) or likely benign or other types of obesity, including obesity-associated with other genetic syndromes and general (polygenic) obesity.
People with obesity due to POMC, PCSK1 or LEPR deficiency become severely obese at a young age. Patients are usually a normal weight at birth, but they gain excess weight because of a genetic defect (an imperfection or anomaly) that affects their level of hunger, ability to feel full or satiated, and energy output (metabolism). These conditions are very rare, with only around 150 reported in the medical literature for all three combined.
Imcivree works by activating areas in the brain that regulate appetite and fullness, causing patients with specific defects in these areas of the brain not to eat as much and to lose weight. The drug also increases resting metabolism (the number of calories the body burns at rest), which can contribute to weight loss. While Imcivree leads to weight loss in patients with obesity-associated with these conditions, it does not treat the genetic defects that cause the conditions or other symptoms or signs.
Imcivree was evaluated in two 1-year studies. The first study enrolled patients with obesity and confirmed or suspected POMC or PCSK1 deficiency while the second study enrolled patients with obesity and confirmed or suspected LEPR deficiency; all patients were six years or older. The effectiveness of Imcivree was determined by the number of patients who lost more than 10 percent of their body weight after a year of treatment.
The effectiveness of Imcivree was assessed in 21 patients, 10 in the first study and 11 in the second. In the first study, 80 percent of patients with POMC or PCSK1 deficiency lost 10 percent or more of their body weight. In the second study, 46 percent of patients with LEPR deficiency lost 10 percent or more of their body weight.
The study also assessed the maximal (greatest) hunger in 16 patients over the previous 24 hours using an 11-point scale in patients 12 years and older. In both studies, some, but not all, of patients’ weekly average maximal hunger scores decreased substantially from their scores at the beginning of the study. The degree of change was highly variable among patients.
The most common side effects of Imcivree include injection site reactions, skin hyperpigmentation (skin patches that are darker than surrounding skin), headache and gastrointestinal side effects (such as nausea, diarrhea, and abdominal pain), among others.
Spontaneous penile erections in males and adverse sexual reactions in females have occurred with treatment. Depression and suicidal ideation have also occurred with Imcivree.
FDA granted orphan disease designation, Breakthrough Therapy designation, and Priority Review for this drug application. FDA granted the approval of Imcivree to Rhythm Pharmaceutical, Inc.
“Our first new drug approval is a major milestone for Rhythm, and we look forward to delivering on the promise of IMCIVREE for patients suffering with obesity due to POMC, PCSK1 or LEPR deficiency,” said David Meeker, M.D., Chair, President and Chief Executive Officer of Rhythm. “With IMCIVREE, we are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the melanocortin-4 (MC4) receptor pathway.”
