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 met the primary endpoint (modified Mayo Score improvement) at each dose tested during the 10 week-induction period of treatment in the randomized double-blind CoTikiS Phase 2 study.
– Highly favorable positive results on the key secondary endpoints demonstrating significantly high rate of clinical and endoscopic remission.
– Across all doses and patient groups, Lusvertikimab demonstrated favorable safety and tolerability profile during the induction period and 24-week additional open label extension treatment (total of 34 weeks) with no specific safety signal identified.
– First anti-IL7R mAb positive efficacy study enabling pathway of future development to potential First-in-Class Interleukin-7 antagonist in autoimmune and inflammatory diseases.
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
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.
Lusvertikimab (Lusv) met the primary efficacy endpoint defined by the improvement of the Modified Mayo Score (MMS)** at week 10 (W10) at the two doses tested and demonstrated statistically significant and clinically meaningful results on key secondary endpoints. A favorable safety profile was observed during both the induction period and during the 6 months of open-label extension period trial. 134 patients were analyzed in the W0-W10 period [group 850mg (50 patients); group 450mg (35 patients); drug group pooled 850mg + 450mg (85 patients); group placebo (49 patients)]. A total of 120 patients treated with Lusvertikimab participated to the additional 24-week OLE treatment period.
* Previous corticosteroids, immunosuppressive agents or previous biological treatments.
** Ulcerative Colitis is a chronic inflammatory disease of the rectum and colon characterized by mucosal inflammation, abdominal pain associated with symptoms and frequency of diarrhea and rectal bleeding. The moderate to severe UC is measured by a Modified Mayo Score (MMS) between 4 and 9, inclusive. The primary endpoint is the mean change at Week 10 from baseline in the Modified Mayo Score, a Disease Activity Index for UC defined by the addition of the stool frequency and the rectal bleeding sub-scores (two patient’s clinical elements as Patient Reported Outcomes) and the endoscopic sub-score (mucosal endoscopy activity), assessed by an endoscopist through a central reading platform.
Safety Profile
Lusvertikimab displayed a good safety profile and was well tolerated, with no difference between both dose groups and placebo in the incidence of drug related serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, severe drug-related AEs, opportunistic infections or infusion reactions during the induction period. In addition, no safety signal was observed in the patient population who received 850mg of Lusvertikimab for an additional 24-week period in the OLE, regardless of the initial randomization groups.
Positive results from Phase 1 clinical study
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