Study shows obesity drug provides benefits beyond weight loss
Imcivree cuts hunger, boosts energy, improves daily life for aHO patients
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aHO patients taking an obesity drug saw quality-of-life improvements. (Photo by iStock)
Treatment with Imcivree (setmelanotide) may offer benefits beyond weight loss, including meaningful improvements in quality of life for people with acquired hypothalamic obesity (aHO), according to findings from a substudy of the Phase 3 TRANSCEND trial.
Previous data from the TRANSCEND (NCT05774756) study showed that Imcivree significantly reduced hunger and body mass index (BMI), a measure of body fat based on height and weight, compared with a placebo. Interviews with a group of trial participants and caregivers suggest these benefits translated into meaningful changes in everyday life.
Nearly all participants who received Imcivree reported or were observed to experience reductions in both hunger and weight after about one year of treatment. Many also had more energy and became more physically active.
Together, these changes were associated with improvements across several aspects of quality of life, including greater participation in school or work, hobbies, and social activities, as well as greater independence and reduced burden on families.
“These findings support the Phase 3 TRANSCEND efficacy outcomes” and suggest “that the impactful changes with [Imcivree] in patients with [aHO] and their caregivers extend beyond body mass index and weight reduction,” the researchers wrote. The study, “Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants,” was published in Frontiers in Behavioral Neuroscience.
Disrupted brain signals
Acquired hypothalmic obesity is caused when damage to the hypothalamus, a part of the brain, disrupts signals that normally regulate hunger and energy expenditure. This includes signaling through the melanocortin-4 receptor (MC4R) pathway, which signals fullness after eating and helps the body burn more calories.
That leads to aHO symptoms of intense and persistent hunger (hyperphagia) while also burning fewer calories at rest. Together, these changes can drive rapid and sustained weight gain that can be extremely difficult to control.
Given as an under-the-skin (subcutaneous) injection, Imcivree is designed to reactivate the MC4R signaling pathway. This is expected to reduce hunger and help patients lose weight. The therapy is approved in the U.S and in the European Union to help support and maintain weight loss in people with aHO ages 4 and older.
Regulatory approvals were largely based on findings from TRANSCEND, which tested a daily subcutaneous injection of Imcivree against a placebo over 52 weeks (about one year) in 120 people with aHO, ages 4 to 66.
But clinical measures such as BMI and hunger scores do not fully capture how treatment affects patients’ everyday lives. To better understand Imcivree’s benefits, the researchers said, “it is necessary to understand the lived experiences” of people with aHO and their caregivers.
The team conducted in-depth interviews near the end of TRANSCEND with 30 U.S. participants or their caregivers. Fourteen participants — four adolescents and 10 adults — were interviewed directly, while caregivers spoke on behalf of another 16, eight younger than 12 and eight aged 12 or older. Overall, 23 had received Imcivree, and seven had received a placebo.
Before entering TRANSCEND, all 30 participants had experienced increased hunger and weight gain after hypothalamic injury. Nearly all (29 of 30) rarely or never felt full, and 28 described intense, unrelenting hunger that led to eating more and having less control over eating.
Patients and caregivers described a constant focus on food and food-seeking behaviors that could strain family relationships and interfere with social activities. One participant recalled that when hunger struck, “nothing else really mattered.” Nearly all participants also experienced reduced energy (29 of 30) and physical activity (28 of 30).
Previous attempts to manage weight had often brought limited results. Eighteen participants had used at least one weight-loss medication, but only five reported losing weight, with the benefits described as limited and temporary.
After 52 weeks in the TRANSCEND trial, 96% of Imcivree-treated participants reported reductions in both hunger and weight, compared with 14% who received the placebo. Patients described feeling hungry less often and less intensely, while caregivers reported fewer requests for food and less food-seeking behaviors.
Improvements extended to energy and activity. Increased physical activity was reported for 78% of Imcivree-treated participants, vs. 14% receiving the placebo, while increased energy was reported for 61% vs. none, respectively.
These changes translated into broader improvements in quality of life. Patients described greater participation in school, work, hobbies, and social activities, as well as improvements in concentration, confidence, self-esteem, and independence. Caregivers also reported improvements in their children’s social and school or work lives,, as well as reduced stress and anxiety for themselves.
All participants reporting reductions in hunger and weight considered the changes meaningful, with some describing them as “life changing.”
“The substudy interview data presented here support and expand on [TRASCEND trial’s] findings, suggesting benefits beyond weight and hunger reduction for individuals with [aHO],” the researchers wrote.
