CM-101 (nebokitug) set for primary sclerosing cholangitis Phase 3 trial
Top-line SPRING data showed gains in several disease-related biomarkers
Chemomab Therapeutics has aligned with the U.S. Food and Drug Administration (FDA) on the best path toward regulatory approval of its investigational therapy nebokitug, previously CM-101, for primary sclerosing cholangitis (PSC).
In an end-of-Phase 2 meeting where data from the Phase 2 SPRING clinical trial (NCT04595825) were discussed, regulators agreed that approving nebokitug would only require a single Phase 3 trial focused on clinical outcomes related to PSC progression.
“We were very pleased by FDA’s positive and collaborative spirit at the meeting and their stated commitment to facilitating the advancement of effective new therapies for PSC,” Adi Mor, PhD, co-founder and CEO of Chemomab, said in a company press release that reported financial results and corporate updates. “We believe that nebokitug could become the first FDA-approved therapy for PSC, addressing the tremendous unmet need in this devastating, often lethal disease.”
Top-line data from SPRING, released about six months ahead of schedule last summer, showed the therapy led to improvements across a range of disease-relevant biomarkers, including those associated with three core aspects of PSC: inflammation, stalled flow of the digestive fluid bile out of the liver (cholestasis), and liver scarring (fibrosis).
Mor said these findings “set the stage” for the meeting with the FDA.
“We and our PSC expert advisers view these Phase 2 data as the strongest in PSC to date,” Mor said. “This is the first time that an investigational drug for PSC has shown improvements across such a wide range of highly relevant disease markers.”
The company plans to release data from SPRING’s open-label extension phase in the coming months.
People with PSC have chronic cholangitis, or inflammation in the tubes that carry bile to the small intestine, known as the bile ducts. This inflammation gives way to bile duct damage over time, leading to cholestasis, and liver damage and fibrosis.
How does nebokitug in PSC?
Nebokitug, the name recently given to CM-101 by the World Health Organization’s International Nonproprietary Names program, is designed to neutralize CCL24, a protein involved in the pro-inflammatory and pro-fibrotic pathways that contribute to PSC. By easing inflammation and fibrosis, the treatment should help ease PSC-related damage, slowing disease progression.
The SPRING study involved 76 adults with PSC who were randomly assigned to receive an infusion into the bloodstream of either nebokitug (10 mg/kg or 20 mg/kg) or a placebo, once every three weeks for just under four months.
The therapy was well tolerated and led to biomarker changes that reflected less liver fibrosis, inflammation, and cholestasis, along with improved liver health, particularly among patients with moderate or advanced disease, or about half the participants.
Data also suggested the treatment could ease pruritus, or itchy skin, a common PSC symptom.
More than 90% of participants who completed the study’s placebo-controlled phase opted to enter its ongoing open-label extension phase, where all are being treated with nebokitug for about 7.5 months.
About the Phase 3 trial
According to a separate company press release, the planned Phase 3 trial will enroll up to 350 PSC patients — most with moderate or advanced disease — who will be randomly assigned to receive 20 mg/kg of nebokitug or a placebo, once every three weeks.
The main goal is to evaluate whether nebokitug can delay clinical events related to disease progression. Enrolled patients will remain in the trial until they have a clinical event and the study will proceed until a predetermined number of events have occurred across the study’s population.
This is the first time the FDA has agreed on this type of primary goal in a PSC trial, which investigators believe is particularly clinically relevant for patients. Previous studies have linked biomarker improvements such as those observed in SPRING with reductions in the type of clinical events that will be measured in the Phase 3 study, according to Chemomab.
“I am delighted that the FDA and Chemomab have aligned on a Phase 3 trial design that focuses on the clinical events that we encounter in caring for PSC patients. These events are clinically relevant and impact our patients’ lives,” said Christopher Bowlus, MD, the Lena Valente Professor and chief of the division of gastroenterology and hepatology at the University of California Davis School of Medicine, in the separate release.
Data on biomarkers of liver and bile duct health will be collected, but no liver biopsies will be required. Moreover, no other confirmatory studies beyond this one will be needed, according to Chemomab.
“This design allows us to significantly accelerate the potential timeline to full approval since there is no need for additional confirmatory studies,” Mor said.
Data from the study could support applications toward nebokitug’s approval in the U.S. and elsewhere. Chemomab is now in discussions with potential strategic partners as it prepares to launch the trial.
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