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.
OSE-127/Lusvertikimab, is a monoclonal immunomodulatory 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.
ABOUT THE OSE-127 (Lusvertikimab) CLINICAL PROGRAM
The Phase 1 showed a good safety and tolerability profile for OSE-127.
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 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.
Ongoing Phase 2 clinical trial in UC with positive interim analysis
The ongoing Phase 2 trial sponsored by OSE Immunotherapeutics is evaluating the efficacy and safety of OSE-127 (Lusvertikimab) versus placebo in patients with moderate to severe active UC who previously failed or lost response or were intolerant to previous treatment(s). A positive interim futility analysis was observed in the prespecified first 50 patients (i.e., 33% of the total patient enrollment in the study) having completed the induction phase. The upcoming major milestone for this Phase 2 clinical trial is expected in December 2023 with the top-line results after the induction phase (primary endpoint at week 10) and in H1 2024 for the first early assessment in maintenance after 6 months of therapy (CoTikiS trial: NCT04882007).
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.
(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