Date: 2012-10-09
Type of information:
phase: 1
Announcement: publication of a paper in Blood demonstrating that CYT107 can enhance immune T cell recovery after a T celldepleted (TCD) allogeneic hematopoietic stem cell transplantation (allo-HSCT)
The paper is titled “Recombinant Human Interleukin-7 (CYT107) Promotes T Cell Recovery Following Allogeneic Stem Cell Transplantation.” The paper by Drs. Perales and van den Brink has been pre-published in the on-line version of the journal Blood (http://www.ncbi.nlm.nih.gov/pubmed/23012326).
Company: Cytheris (France)
Product: CYT107 (Recombinant human interleukin-7)
Action mechanism: Recombinant human interleukin-7 (CYT107) is a critical immune-modulator for immune T-cell recovery and enhancement. As a growth factor and cytokine physiologically produced by marrow or thymic stromal cells and other epithelia, IL-7 has a critical and, at some steps, a non-redundant stimulating effect on T lymphocyte development, notably on thymopoïesis and, downstream from the thymus, on homeostatic expansion of peripheral T-cells.
Disease: patients undergoing T celldepleted (TCD) allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Therapeutic area: Transplantation
Country:
Trial details: The study was a phase I trial of r-hIL-7 (CYT107) in recipients of TCD allo- HSCTs. Twelve patients were treated with escalating doses of CYT107 administered weekly for 3 weeks.
Latest
news: Cytheris, a privately held clinical-stage biopharmaceutical company focused on treating lymphopenia driven
diseases, has announced the publication of a paper demonstrating that CYT107, glycosylated recombinant human interleukin-7 (glycosylated r-h-IL7) can enhance immune T cell recovery after a T celldepleted
(TCD) allogeneic hematopoietic stem cell transplantation (allo-HSCT).
The study detailed in the paper demonstrated an increase in functional T cells, including viral-specific T cells that recognize CMV, and enhanced T cell receptor diversity. Additionally, there was no significant GVHD or other serious toxicity. It details the phase I study performed in 12 patients undergoing TCD allo-HSCT.
At baseline, patients were profoundly lymphopenic. CYT107 induced a doubling in CD4+ and CD8+ T cells. The main effect of IL-7 was an expansion of effector memory T cells, the predominant subset identified in Cytheris patients. There was no significant effect on CD4+CD25+FoxP3+ T cells, NK or B cells. Importantly, there were not only quantitative increases in T cells after a short course of IL-7, but an increase in functional T cells, including viral-specific T cells that recognize CMV.
Enhanced TCR diversity was also observed after treatment. The study drug was well tolerated with only one patient developing acute skin GVHD. The results indicate that r-hIL-7 can enhance immune recovery after a TCD allo-HSCT without causing significant GVHD or other serious toxicity.
There is currently no marketed drug for the treatment of this condition.
Cytheris has obtained scientific advice for a pivotal phase IIb study protocol with CYT107 in HIV-related PML. Cytheris reached an agreement with the EMA on the key study endpoints. Cytheris will start this phase IIb study, intended to be the pivotal registration study, in early 2013.
