Cytheris SA has announced the publication of a paper demonstrating that Cytheris' CYT107, glycosylated recombinant human interleukin-7 (glycosylated r-h-IL7) can enhance immune T cell recovery after a T cell-depleted (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.
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).
It details the phase I study performed in 12 patients undergoing TCD allo-HSCT. The paper is titled "Recombinant Human Interleukin-7 (CYT107) Promotes T Cell Recovery Following Allogeneic Stem Cell Transplantation."
"Lymphopenia post-HSCT is a serious problem leading to mortality and morbidity, notably from potentially life-threatening infections and relapse. Several of these infections are resistant to standard treatments or have no treatment at all," said Dr Miguel Perales, MD, Director, Adult Bone Marrow Transplantation Fellowship, Memorial Sloan-Kettering Cancer Center, New York.
Dr Perales continued, "CYT107 is the first agent to demonstrate the ability to reverse post-transplant lymphopenia without increasing risks. It may offer the possibility to restore the T-cell immune system to fight these serious and often fatal infections, and improve survival."
"These data confirm the potential seen in other studies for CYT107 to treat lymphopenia and lymphopenia driven diseases. PML, Cytheris lead indication for CY107, is a rare and devastating disease with one year mortality of 40-50 per cent that is caused by reactivation of latent JC virus in lymphopenic patients," said Therese Croughs, chief medical officer at Cytheris.
Croughs continued, "We have already gathered clinical data supporting the efficacy and safety of CYT107 in PML through several compassionate use treatments. These new data in TCD allo-HSCT patients are particularly interesting in the context of PML due to the virus-specific immune responses. They also open the future possibility of use of CYT107 to treat resistant viral infections, such as CMV, in post-transplant and other lymphopenic populations."
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. 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.
"The results announced today strongly support the Cytheris strategy to conduct a pivotal registration study of CYT017 in PML," said Damian Marron, chief executive officer at Cytheris. "PML affects around 4,000 people in the US and EU alone. Bringing a treatment to this population would not only save and change patients' lives but would also respond to the pharmaceutical industry's desire to develop breakthrough drugs for targeted indications."
PML is a severe demyelinating disease of the central nervous system caused by the JC virus. It occurs in many conditions leading to severe lymphopenia such as HIV infection, some cancers and organ transplantation treated with immunosuppressive therapies.
PML is a very rare disease, affecting around four out of a million individuals. There is currently no marketed drug for the treatment of this devastating 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.
Additionally, The European Commission has granted an orphan designation for Cytheris' CYT017, glycosylated recombinant human interleukin-7 (glycosylated r-h-IL7), for the treatment of Progressive Multifocal Leukoencephalopathy (PML).