Lusvertikimab (OSE-127)
a humanized monoclonal antibody, is an antagonist of the alpha chain of the interleukine-7 receptor, CD127, present on T effector cells, thus down regulating the immune activity.
Lusvertikimab (OSE-127) is a monoclonal immuno-modulatory antibody targeting the CD127 receptor, the alpha chain of the interleukin-7 receptor (IL-7R) that induces a powerful antagonist effect on effector T lymphocytes. Interleukin-7 is a cytokine which specifically regulates the tissue migration of human effector T lymphocytes. The blockage of IL-7R prevents the migration of pathogenic T lymphocytes while preserving regulator T lymphocytes which have a positive impact in autoimmune diseases.
Lusvertikimab was evaluated in a Phase 2 clinical trial, named CoTikiS, in patients with moderate to active ulcerative colitis (UC). Efficacy and safety clinical results from the 10-week induction period were presented at the 2025 congress of ECCO (European Crohn’s and Colitis Organization) in February. Clinical results from the 24-week open-label extension period (OLE) were presented at the DDW (Digestive Disease Week) conference in San Diego on May 5, 2025.
These results have shown that over >90% of people living with UC who achieved a clinical response after 10 weeks of treatment with Lusvertikimab maintained symptomatic remission for an additional 24 weeks. Lusvertikimab was well tolerated over the OLE period.
Full clinical data package for study demonstrates potential of first-in-class monotherapy with a novel mechanism of action in chronic and inflammatory diseases.
Besides immuno-inflammation, Lusvertikimab has also demonstrated great therapeutic potential in immuno-oncology through positive efficacy preclinical results in Acute Lymphoblastic Leukemia (ALL), a very aggressive tumor. Novel targeted immunotherapies are urgently needed to address relapsed/refractory (R/R) form of the disease, especially in T-ALL where the need for novel therapies is significant.
ABOUT THE LUSVERTIKIMAB (OSE-127) CLINICAL PROGRAM
The randomized, double-blind Phase 2 clinical trial CoTikiS has evaluated the efficacy and the safety of Lusvertikimab versus placebo in 136 patients with moderate to severe active UC who failed or lost response to previous treatment(s)*. CoTikiS is a 50-week study, with a 10-week induction period evaluating two doses (450mg or 850mg) of Lusvertikimab against placebo, a 24-week additional open label treatment extension period (OLE) during which all subjects received Lusvertikimab 850mg infusions every 4 weeks and a 16-week safety follow-up period free of treatment.
*Previous corticosteroids, immunosuppressive agents or previous biological treatments.
These results have shown that over >90% of people living with ulcerative colitis (UC) who achieved a clinical response after 10 weeks of treatment with Lusvertikimab maintained symptomatic remission for an additional 24 weeks.
Of the participants who did not reach symptomatic remission in the first 10 weeks of treatment with either dose of Lusvertikimab, 61% had achieved remission after a further 24 weeks on the 850 mg dose.
OVERVIEW OF CoTikiS OLE FINDINGS
Lusvertikimab demonstrated a deepening of treatment response and durable response, with a high rate of symptomatic remission.
– 89% of participants entered the OLE period and 87% of them completed the study.
– Rates of symptomatic remission improved for all dose groups in the OLE period, suggesting a deepening of efficacy. For participants who had received the 850 mg dose from the beginning of the study, rates plateaued after Week 14; rates of symptomatic remission continued to improve through week 26 for the 450 mg induction group (10 weeks of 450 mg, 16 weeks of 850 mg dosing) and through week 34 for the group receiving placebo in the induction phase (10 weeks of placebo, 14 weeks of 850 mg Lusvertikimab).
– 92% of participants who had achieved symptomatic remission with either dose of Lusvertikimab in the induction period maintained it through the OLE period7 including 100% of those who achieved remission in the 850 mg dose group.
– 61% of participants who had not achieved symptomatic remission with either dose of Lusvertikimab in the induction period went on to achieve it during the OLE period.
– 85% of participants who had been in the placebo arm during the induction period went on to achieve symptomatic remission after receiving 850 mg in the OLE period.
– 82% of participants achieved remission of rectal bleeding by the end of the OLE.
– Lusvertikimab was well tolerated over a 34-week treatment period, with a good safety profile and without a higher rate or severity of infection.
– Lusvertikimab achieved statistical significance on the primary and secondary endpoints in moderate to severe active ulcerative colitis (UC) patients during the 10-week induction period of treatment in the randomized, double-blind CoTikiS Phase 2 study. These results were presented in the Top 10 congress highlights oral plenary session at ECCO 2025.
– Lusvertikimab demonstrated high rates of clinical and endoscopic remission after 10 weeks of treatment, along with clinically meaningful histological improvement and Histo-Endoscopic Mucosal Improvement (HEMI) rates.
– Treatment with Lusvertikimab significantly reduced fecal calprotectin (FCP) after 10 weeks of treatment, an objective biomarker of mucosal inflammation in UC patients and an early predictor of endoscopic and histological responses.
– Statistically significant efficacy was demonstrated in clinical and endoscopic remission in the UC patient subgroup with high baseline FCP (>250µg/g).
– A good safety and tolerability profile was observed with no clinically relevant safety signals.
Positive results from Phase 1 clinical study
The Phase 1 had shown a good safety and tolerability profile for Lusvertikimab
An article, selected as ‘Top Read’ for the March 15th issue, was published online in ‘The Journal of Immunology’ (online). The publication, entitled
First-in-Human Study in Healthy Subjects with the Non-Cytotoxic 1 Monoclonal Antibody OSE-127, a Strict Antagonist of the IL-7Rα
reports on the Phase 1 positive results. These showed a good safety and tolerability profile for Lusvertikimab (OSE-127), with no signs of significant lymphopenia, cytokine release syndrome or T-cell compartment alterations. All pharmacokinetic and pharmacodynamic parameters were consistent and demonstrated a dose-proportionality across the several dose-levels up to 10 mg/kg. A decreased IL-7 pathway gene signature in human peripheral blood cells has been demonstrated confirming the efficient blockade of the target.
UC is a debilitating and chronic inflammatory bowel disease which affects 3.3 million patients in US, Europe and Japan (1) representing 12.2 per 100,000 people by year (2). Despite broad options, remission rates are only 25-30% (3) leaving most patients without satisfactory treatments. The disease is characterized by a heavy burden on patients’ lives with a strong medical need for new therapeutic options.
(1) EvaluatePharma
(2) Updated Incidence and Prevalence of Crohn’s Disease and Ulcerative Colitis in Olmsted County, Minnesota (1970-2011). Loftus EV et al. October 2014.
(3) Drugs Context. 2019; 8: 212572 –doi: 10.7573/dic.212572