Olamkicept induces clinical response in nearly 60% of patients with active UC
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Key takeaways:
- Biweekly infusions of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks.
- Drug-related adverse events were more common in patients receiving olamkicept.
Biweekly infusions of olamkicept 600 mg increased the likelihood of clinical response and mucosal healing at 12 weeks in patients with active ulcerative colitis compared with placebo, according to results published in JAMA.
“Olamkicept, a first-in-class, selective inhibitor of the s-interleukin-6R/IL-6 complex, is a dimer formed by fusing two complete extracellular domains of gp130 to human IgG1Fc that inhibits IL-6 trans-signaling by binding to and neutralizing the sIL-6R/IL-6 complexes but does not block classic IL-6 signaling,” Shenghong Zhang, MD, of the department of gastroenterology at The First Affiliated Hospital at Sun Yat-sen University in China, and colleagues wrote. “A phase 2a, open-label trial (FUTURE) over 12 weeks in 16 patients with active Crohn’s disease or ulcerative colitis demonstrated distinct changes in mucosal pSTAT3 levels in biopsies from serial colonoscopies and was not associated with significant safety concern.”
To further assess the effect of olamkicept as induction therapy, Zhang and colleagues conducted a randomized, double-blind, placebo-controlled phase 2 study of 91 patients (mean age, 41 years; 27.5% women) with active UC and inadequate response to prior conventional therapy.
Participants were randomly assigned to receive biweekly IV infusions of olamkicept 600 mg (n = 30), olamkicept 300 mg (n = 31) or placebo (n = 30) for 12 weeks, with the primary outcome of clinical response using total Mayo score at week 12.
Of 79 participants who completed the trial, more patients in the olamkicept 600 mg (58.6%) and 300 mg (43.3%) groups achieved clinical response compared with placebo (34.5%), with an adjusted difference vs. placebo of 26.6% (90% CI, 6.2-47.1) and 8.3% (90% CI, –12.6 to 29.1), respectively.
Researchers also reported that 20.7% and 6.7% of patients on olamkicept 600 mg and 300 mg, respectively, achieved clinical remission based on total Mayo score compared with no patients on placebo, with a significant adjusted difference of 19.9% in the 600 mg group vs. placebo (90% CI, 12.5-27.3). Additionally, a greater number of patients who received olamkicept achieved mucosal healing (34.5% vs. 10% vs. 3.4%).
Among patients in the 600 mg group, 16 of 25 secondary outcomes were “statistically significant” compared with placebo, as were six of 25 outcomes in the 300 mg group.
Treatment-related adverse events occurred in 53.3%, 58.1% and 50% of patients, respectively, the most common of which were presence of bilirubin in the urine, hyperuricemia and elevated aspartate aminotransferase levels. No deaths were reported.
“Among patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo,” Zhang and colleagues concluded. “Further research is needed for replication and to assess longer-term efficacy and safety.”
Perspective
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Miguel Regueiro, MD
Olamkicept represents a novel mechanism of action for the treatment of ulcerative colitis. This is a first-in-class, selective inhibitor of the s-interleukin-6R/IL-6 complex that is being studied for UC.
The study found a dose-dependent, higher rate of response and remission in patients receiving olamkicept compared with placebo. The true question will be whether this therapy is more effective than any of our existing therapies for UC. A question that certainly cannot be answered by this study, but based on the study findings, this medication seems to have similar response rates to other UC medications on the market.
A potential challenge with this therapy is the need for infusion every 2 weeks, something that may be difficult for our patients. Hopefully, one day, we move closer to a precision-medicine approach to the treatment of IBD patients and the administration of medications based on a patient’s molecular profile.
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