The medical need: steroid-resistant or corticosteroid-dependent aGvHD
Formerly called bone marrow transplant, Hematopoietic Stem Cell Transplantation (HSCT) is the last therapeutic option for patients with certain blood cancers or severe immunodeficiency. In practice, the treatment is designed to replace the diseased blood cells of the patient with the hematopoietic stem cells of a matching donor (allograft).
Once grafted, these stem cells will produce new healthy and functional blood cells, including white blood cells that will allow patients to bridge their immune deficiency or to eliminate surviving cancer cells.
If this technique has made considerable progress in 60 years, half of transplant recipients are still victims of complications: side effects of conditioning pretreatment (that aims to prevent transplant rejection), long-term susceptibility to infections and GvHD. In the latter case, the donor’s over-active T-cells «turn against» the patient’s tissues: mucous membranes, skin, gastro-intestinal tract, liver and lungs. The acute form appears just after the transplant, the chronic form occurring several months later (preceded or not by an acute GvHD episode).
Affecting between 30 to 50% of patients, GvHD is the main complication of hematopoietic stem cell transplantation. To halt this disease, physicians use corticosteroids. The fact remains that some 30 to 50% of aGvHD patients are refractory or dependent to the steroid treatment.
To date limited therapeutic options are available for these patients with no standard treatment approved so far in Europe and only one in the US.
Inolimomab is an anti-IL-2 Rα monoclonal antibody active as an immunotherapy product for the treatment of steroid-refractory acute GvHD.
In acute GvHD, activated T cell lymphocytes from the allograft’s donor recognize and attack recipient tissues. T cell lymphocyte activation and proliferation is governed by the key IL-2/IL-2 receptor (IL-2 R) pathway.
By recognizing the subunit α of the IL-2 Receptor complex (IL-2 Rα) which is upregulated on T cells upon activation, inolimomab blocks the binding of the cytokine IL-2 on IL-2 Rα thereby inhibiting IL-2 signalling and donor T cell proliferation.
The efficacy of inolimomab in aGvHD relies on its specific potent immunosuppression on T cell lymphocytes through the blocking of the IL-2/IL-2 Rα pathway triggering the disease.
Inolimomab (LEUKOTAC®) Mechanism of Action
Based on the outcomes of the INO107 Phase III clinical trial (see the poster presented at EBMT2018), notably a significant increase in overall survival at one year (+ 37%) and a significantly more favourable safety profile as compared to the off-label drugs currently used by clinicians, ELSALYS BIOTECH acquired the rights of inolimomab (LEUKOTAC®) in 2017 with the aim to quickly reach the market.
The monoclonal antibody has been analyzed for long-term Phase III survival data (published in Blood Advances in January 2019).
Considering that patients are currently facing a therapeutic emergency, based on these data and with the full support of many clinicians specialized in this pathology who have already administered inolimomab (LEUKOTAC®), ELSALYS BIOTECH aims at obtaining a marketing authorisation (AMM) in Europe by 2022.
Key achievements of Inolimomab
The French National Agency for the Medicines and Health Products Safety (ANSM) granted a Temporary Authorisation for Use (ATU) so-called cohort ATU (cATU) for LEUKOTAC® (inolimomab) for the treatment of graft-versus-host disease, corticosteroid-resistant or corticosteroid-dependent, with grade II-IV on December 24, 2019 (see press release issued January 9, 2020).
In June 2020, FDA accepted the Biologics License Application (BLA) for inolimomab (LEUKOTAC®) under the RTOR pilot program which is a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible. (see press release issued July 23, 2020).
Inolimomab (LEUKOTAC®) received Orphan Drug Designation in Europe (March 2001) and in the U.S. (October 2002) and has been administreted in several hundred patients included in clinical trials or treated via named patient Temporary Authorization for Use (“ATU nominative”) until its production was suspended in November 2015.