New treatment for acquired obesity sees strong early US uptake
More than 400 patient start forms submitted since Imcivree’s March approval
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Medications shown in a shopping cart represent access to prescription treatments, as more than 400 patient start forms have been submitted for Imcivree since its U.S. approval for acquired hypothalamic obesity in March. (Image from iStock)
Since Imcivree (setmelanotide) was approved in the U.S. in March to support weight loss in people ages 4 and older with acquired hypothalamic obesity (aHO), its maker, Rhythm Pharmaceuticals, has received more than 400 patient forms seeking to start treatment from about 300 prescribers.
“Rhythm continues to demonstrate strong commercial and clinical development progress, highlighted by a strong start in the U.S. launch of IMCIVREE for acquired hypothalamic obesity (HO),” David Meeker, MD, Rhythm’s chairman, president, and CEO, said in a company press release. “The demand we are seeing from both patients and physicians reinforces the significant unmet need in acquired HO and the opportunity for IMCIVREE to transform the treatment paradigm for this devastating disease.”
Imcivree rollout expands beyond the U.S.
Imcivree was also recently approved for the same indication in the European Union, and it is currently under review by regulators in Japan. If approved, Rhythm expects to commercially launch the therapy in Japan before year’s end, with country-level launches in Europe slated for 2027.
“With strong commercial execution in the United States and meaningful launches in [aHO] upcoming in Japan and Europe, we remain focused on expanding treatment options for patients,” Meeker said.
Rhythm also announced preliminary data from the Phase 2 portion of an ongoing Phase 1/2 clinical trial (NCT06239116) evaluating its next-generation candidate for aHO, RM-718, which works similarly to Imcivree but is designed to be given once weekly instead of once daily.
“The magnitude of BMI [body mass index] reduction observed to date is consistent with what we have seen with [Imcivree] and bivamelagon at similar treatment durations,” Meeker said in a separate press release announcing the trial results. BMI is a measure calculated using a person’s weight and height and is commonly used as a proxy for body fat.
Bivamelagon is Rhythm’s experimental oral treatment for aHO that also has a similar mechanism of action to Imcivree. The company plans to start a pivotal Phase 3 trial evaluating bivamelagon in people with aHO by year-end. Pivotal trials are designed to produce robust data that, if positive, may be used to support requests for the therapy’s approval.
aHO is marked by damage to the hypothalamus, a region of the brain, that leads to reduced activity of a protein called the melanocortin 4 receptor (MC4R), which normally helps regulate hunger and energy expenditure.
Imcivree is an activator, or agonist, of the MC4R protein that is designed to restore normal activity of this signaling pathway. The therapy is given once daily by an under-the-skin, or subcutaneous, injection.
In addition to aHO, the therapy is also approved in the U.S. for several other forms of rare obesity, including Bardet-Biedl syndrome.
Imcivree’s regulatory approvals for aHO were based mainly on data from an international Phase 3 clinical trial called TRANSCEND (NCT05774756), which tested the therapy against a placebo in more than 100 people with this form of rare obesity. Full results from the trial were published last month, showing that Imcivree significantly outperformed placebo in promoting weight loss.
Weekly therapy shows early BMI reductions
Rhythm is also developing RM-718 as a potential therapy for aHO. Like Imcivree, RM-718 is designed to activate the MC4R protein — but instead of requiring daily injections, RM-718 is designed to be given once weekly by injection.
The Phase 1/2 trial is testing RM-718 in up to 150 participants across several groups, including otherwise healthy adults with obesity and people with aHO or Prader-Willi syndrome, the most common genetic cause of life-threatening childhood obesity.
According to newly announced preliminary results, 11 people with aHO were enrolled in the ongoing open-label trial. Among the seven with 16-week data, average BMI decreased by 11.6% from baseline.
Rhythm said the BMI reductions seen in these participants were comparable to those seen with Imcivree and bivamelagon, the company’s investigational oral therapy that also works by activating the MC4R pathway.
RM-718 was generally well tolerated; the most commonly reported adverse events were injection site reactions, nausea, and vomiting. Two mild instances of hyperpigmentation (darkened skin) were documented, and both were limited to the injection site. No generalized hyperpigmentation was reported. Hyperpigmentation is a common side effect of Imcivree.
“These encouraging results suggest that RM-718 has the potential to deliver clinically meaningful BMI reductions in patients with acquired HO,” Meeker said. “Importantly, we have observed very limited hyperpigmentation, with two mild cases reported isolated to the injection site. We look forward to continuing to advance RM-718 as a potential next-generation treatment option for patients living with rare MC4R pathway diseases.”
