Palatin Technologies has announced positive topline results from its Phase 2 study evaluating PL8177, an oral selective melanocortin-1 receptor (MC1R) agonist, in patients with active ulcerative colitis (UC). The eight-week trial demonstrated significant clinical benefits with an excellent safety profile, potentially offering a new treatment approach for this chronic inflammatory bowel disease.
The randomized, double-blind, placebo-controlled study enrolled twelve patients with active ulcerative colitis, defined as having a Mayo Endoscopic Total Score of at least two. Nine patients received PL8177 and three received placebo for eight weeks of treatment.
Significant Clinical Efficacy Demonstrated
After eight weeks of treatment, PL8177 showed impressive efficacy across multiple endpoints:
- Clinical remission was achieved in 33% (3 of 9) of PL8177-treated patients versus 0% (0 of 3) on placebo
- Clinical response was demonstrated in 78% (7 of 9) of PL8177-treated patients versus 33% (1 of 3) on placebo (p<0.005)
- Symptomatic remission was achieved in 56% (5 of 9) of PL8177-treated patients versus 33% (1 of 3) on placebo
The clinical remission definition followed FDA Guidance (April 2022), requiring a modified Mayo Score of 0 to 2, with specific subscores for rectal bleeding, stool frequency, and endoscopy.
In a subset analysis of patients with more moderate disease at baseline (defined by inflammation in all three colon segments), 60% of PL8177-treated patients showed improvement in all three segments, and 80% showed improvement in at least two segments. No placebo patients showed similar improvements.
"We are thrilled with the positive results in this study, especially the meaningful and high rates of achievement for clinical remission and clinical response. These endpoints align with the FDA's recommended primary and key secondary endpoints for evaluating efficacy in UC clinical trials," stated Carl Spana, Ph.D., President and CEO of Palatin. "Most patients showed significant symptom and endoscopic score improvements after just eight weeks of treatment."
Novel Mechanism of Action with Excellent Safety Profile
PL8177 represents a novel approach to treating ulcerative colitis through MC1R agonism. The drug is designed to target melanocortin-1 receptors on the surface of cells lining the colon. In Phase 1 trials, the oral formulation was shown to effectively reach the colon without systemic absorption.
Importantly, treatment with oral PL8177 was well tolerated with no treatment-related side effects reported. This safety profile could provide a significant advantage over current standard treatments.
"Given these positive results, once-daily oral PL8177 could be a safe and effective alternative to immunosuppressive and steroid therapies, which have significant safety and tolerability concerns," Dr. Spana added.
Expert Perspective on Unmet Need
Dana J. Lukin MD, PhD, Clinical Director of the Jill Roberts Center for Inflammatory Bowel Disease at Weill Cornell Medicine-New York Presbyterian Hospital, emphasized the importance of these findings: "Despite the advances in therapy for UC, I frequently see patients who struggle with this condition and their symptoms. This is why there remains a strong need for new treatment options that work in different ways."
Dr. Lukin continued, "Seeing a good percentage of patients treated with PL8177 achieve strong results for clinical remission and clinical response in this short study on UC patients is a compelling indicator that melanocortin-1 receptor agonists could be a promising treatment option for UC."
Study Design and Limitations
The Phase 2 PL8177 study was originally planned to enroll up to 28 patients, with an interim analysis after 12-16 participants. Palatin stopped enrollment at 12 patients to accelerate out-licensing discussions and redirect resources to development of its melanocortin obesity assets. Due to the smaller sample size, the study was not powered to show statistical significance across all endpoints, though clinical response did achieve statistical significance (p<0.005).
Potential Commercial Pathway
Palatin has indicated that several major pharmaceutical companies have shown strong interest in their UC program. Dr. Spana noted, "The strong data from this Phase 2 study, along with the positive Phase 1 findings and robust preclinical data, provides meaningful evidence to support the advancement of a melanocortin-1 receptor agonist as a potential treatment for ulcerative colitis. We believe these positive Phase 2 results in PL8177 treated patients, for the critical efficacy endpoints of both clinical remission and clinical response, could help solidify a potential licensing deal."
Ulcerative Colitis: A Significant Unmet Need
Ulcerative colitis is a chronic inflammatory disease of the large intestine that affects approximately 1.25 million individuals in the United States, with over 350,000 diagnosed with moderate-to-severe disease. The condition causes inflammation and ulcerations in the colon, leading to symptoms such as abdominal pain, persistent diarrhea, bloody stool, and urgency to use the bathroom.
Current treatments are not effective for many patients with moderate-to-severe ulcerative colitis, and severe cases may require surgical removal of the colon. The disease course varies between patients and can lead to serious complications, including cancer.
About PL8177 and Melanocortin Receptor Agonists
PL8177 is a synthetic cyclic heptapeptide that acts as a potent, selective agonist at the human melanocortin-1 receptor. The melanocortin receptor system has effects on inflammation, immune system responses, metabolism, food intake, and sexual function.
The drug has demonstrated efficacy in multiple animal inflammatory bowel disease models. Palatin's oral formulation of PL8177 was designed to be protected from degradation in the stomach and small intestine, allowing delivery to the colon over an extended period.
Additional findings from the Phase 2 trial are expected to be shared at an upcoming scientific conference. The trial is registered at clinicaltrials.gov under the identifier NCT05466890.
