Connect Biopharma Phase II trial on a potential drug for adults with moderate-to-severe ulcerative colitis may have failed to meet its primary endpoint, but the company isn’t giving up yet.
Connect Biopharma’s Phase II trial of a potential drug for adults with moderate-to-severe ulcerative colitis may have failed to meet its primary endpoint, but the company isn’t giving up yet.
At Week 12 of the trial assessing CBP-307, the measure of least squares (LS) mean change from baseline based on Mayo Score did not reflect a significant change. The Mayo Score covered rectal bleeding, stool frequency and endoscopy ratings.
Patients given 0.2 mg of CBP-307 logged an LS mean change of -2.65, which was not far from the -2.01 recorded in the placebo group. Given this outcome, the researchers said that further study is necessary. 145 patients from more than 60 sites in four countries participated in this randomized, multi-center trial.
“Ulcerative colitis is a serious chronic condition with continued unmet need. The overall 12-week results for CBP-307 demonstrate the therapeutic potential to induce a significant treatment response consistent with clinical data of other S1P modulators in patients with UC,” commented Dr. David T. Rubin, chief of the gastroenterology, hepatology and nutrition section of the University of Chicago Medicine.
Ulcerative colitis affects around 600,000 to 900,000 people in the United States alone. If left unaddressed, the disease progresses to organ damage, typically presenting as dysplasia. Untreated UC can also eventually lead to cancer. There are treatments available for UC, but these are limited. 70% to 80% of patients often fail to achieve clinical remission.
CBP-307 is an orally administered small molecule that can modulate sphingosine 1-phosphate receptor 1 (S1P1), a target in treating a number of inflammatory illnesses, UC included.
However, despite failing to achieve the primary endpoint, CBP-307 managed to hit some secondary endpoints, with 28.3% of participants reaching clinical remission versus 9.6% in the placebo group based on adapted and completed Mayo Scores.
Other improvements observed included a change in the complete Mayo Score from baseline to week 12 of -3.67 versus -2.74 for those on placebo. Clinical response, still based on the complete Mayo Score, was 52.8% in the CBP-307 group versus 30.8% in the others.
In addition, some drug-related treatment-emergent adverse events (TEAEs) were seen in the therapy group, with 66% reporting issues compared to 38.5%. Grade 3 or higher TEAEs were at 7.5% in CBP-307 versus 7.7%, while serious TEAEs were at 3.8% versus 5.8%, respectively. Overall, the researchers said the drug is well tolerated but noted that more trials are necessary to establish the candidate’s efficacy and safety.
Zheng Wei, Ph.D., co-founder and chief executive officer of Connect Biopharma, said the company plans to “explore strategic partnerships” in the future to conduct future trials with the asset.
“These top-line, induction phase data demonstrate the potential for CBP-307 to provide benefit to patients living with moderate-to-severe UC. Together, with recent positive results from our Phase II study of CBP-201 in atopic dermatitis, they support our approach to T cell-driven research in immunological pathways,” Wei noted.
