OSE-127/Lusvertikimab
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.
• Lusvertikimab demonstrates significant efficacy during the 10 week-induction phase of treatment, in the randomized double-blind CotiKis phase 2 study
• Favorable safety and tolerability profile in the whole patient population across the two doses tested and during the open label phase of treatment
• First anti-IL7R mAb positive efficacy study enabling pathway of future development to potential First-in-Class Interleukin-7 antagonist
Besides immuno-inflammation, OSE-127 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 OSE-127 (Lusvertikimab) CLINICAL PROGRAM
- First positive efficacy results from Phase 2 study in Ulcerative Colitis (UC)
- Positive results from Phase 1 clinical study
The first positive results from CoTikiS randomized, double-blind, placebo-controlled, Proof of Concept Phase 2 study of Lusvertikimab, a pure antagonist of IL-7 receptor, demonstrated significant efficacy results measured by the improvement of the Modified Mayo Score (at week 10 primary endpoint of the treatment induction phase) in UC. A favorable safety profile was observed during both the induction phase and during the 6 months of open-label extension phase trial.
Primary endpoint: a significant decrease of the Modified Mayo Score (MMS) is achieved versus placebo at week 10:
. The 850 mg group (n=50, Placebo n=49) in the principal analysis obtained significant results at week 10 versus Placebo on the improvement of the MMS with a -0.82 (95%CI: -1.63. -0.01) differenceμ in treatment effect between lusvertikimab and placebo (p=0.047).
. The 450 mg group (n=35, Placebo n=49) obtained significant results versus placebo (the 450 mg group was considered as exploratory as prematurely interrupted***) with a differenceμ of -1.17 (95%CI: -2.18; -0.16) between lusvertikimab and placebo (p=0.023).
The global treatment effect is significant considering the 450+850mg groups together versus placebo showing a differenceμ of -0.88 (95%CI: -1.64; -0.12) between lusvertikimab and placebo (p= 0.024).
Safety results: no safety signal was reported by the Data Safety Monitoring Board during the trial. Both doses of lusvertikimab show favorable safety profile in comparison with placebo, with similar rates of adverse events across the 3 treatment groups.
The Phase 1 had shown 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.
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