Palatin to test 2 obesity-targeting drugs for PWS in clinical trials this year
Developer's MC4R-based therapies aim to suppress patients' hunger
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Palatin Technologies plans to move two obesity-targeting drugs — experimental therapies designed to activate the melanocortin-4 receptor (MC4R) protein, which is involved in appetite and energy balance — into clinical testing in people with Prader-Willi syndrome (PWS) this year.
Planned trials will also test the company’s candidates in people with hypothalamic obesity, a disorder that, like PWS, is marked by insatiable hunger. Both conditions are characterized by obesity and have significant unmet medical needs.
“Palatin continues to advance its MC4R-based obesity pipeline, with our oral small-molecule MC4R agonist [activator], PL7737, on track to enter clinical evaluation in the first half of this year, and a long-acting peptide MC4R agonist expected to initiate clinical development in the second half of the year,” Carl Spana, PhD, Palatin’s president and CEO, said in a company press release that provided corporate updates for the second quarter.
Peptides are short chains of amino acids, the building blocks of proteins, and these are engineered to remain active in the body for extended periods. Palatin hopes to test its own MC4R agonist, which has yet to be selected, in a clinical trial later this year, according to the release.
“As we progress these programs, we remain focused on delivering differentiated product profiles designed to enhance patient tolerability, including the potential for reduced gastrointestinal side effects, while minimizing off-target effects such as hyperpigmentation [dark skin patches],” Spana said.
Starting in childhood, PWS often causes excessive hunger, or hyperphagia, and an obsession with food. This can lead to overweight or obesity, along with other symptoms such as delays in development, learning difficulties, problems with sleep, and behavioral challenges. In hypothalamic obesity, weight gain is caused by problems in the hypothalamus, the region of the brain that regulates hunger and thirst.
Melanocortin receptor agonists work by activating receptor proteins in the melanocortin system, a group of hormones that regulate energy needs, among other functions. There are five melanocortin receptors, called MC1R through MC5R.
Targeting MC4R protein aims to limit weight gain in PWS
Targeting MC4R is considered promising because it is present on nerve cells that regulate appetite and energy use. Genetic mutations that suppress MC4R signaling can cause excessive hunger, reduced energy expenditure, and weight gain, and this pathway is believed to be dysfunctional in many genetic forms of obesity, including PWS.
As such, MC4R activators are expected to limit weight gain driven by hyperphagia. In a separate Phase 2 trial, Rhythm Pharmaceuticals’ MC4R agonist setmelanotide has shown promise in easing hyperphagia and lowering body weight in children and adults with PWS. Setmelanotide is already approved in the U.S. under the brand name Imcivree for treating several forms of genetic obesity.
Palatin is aiming to develop MC4R agonists that are tolerated better by patients and have the potential to cause fewer gastrointestinal side effects and skin hyperpigmentation — a known side effect of MC4R agonists.
PL7737 is an experimental oral therapy that’s now completing required preclinical studies to confirm its safety before it can be tested in first-in-human studies. Data from animal studies to date show that PL7737 is well absorbed when taken by mouth and leads to significant weight loss.
The company plans to submit an investigational new drug application (IND) to the U.S. Food and Drug Administration, seeking clearance for a Phase 1 trial to test increasing single and multiple doses of PL7737 in people with PWS or hypothalamic obesity. The company expects to launch that study in the first half of this year.
In parallel, Palatin plans to file an IND for clearance of a similarly-designed Phase 1 trial to test a yet-to-be-selected next-generation peptide MC4R agonist that will be administered via subcutaneous, or under-the-skin, injections once weekly. Both the regulatory submission and the trial’s start are expected in the second half of the year.
