– Statistically significant increase in Overall Survival and reduction in Transplant Related Mortality observed in comparison to a historical control group
– Zero patients developed grade III-IV acute Graft-versus-Host-Disease upon infusion of ATIR101™
– Analysis of full read out of primary endpoint data anticipated to be reported in April 2016
Amsterdam, The Netherlands, December 7, 2015 – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company developing innovative T-cell immunotherapy treatments for blood cancers and inherited blood disorders, today presents data from its ongoing Phase II clinical trial in leukaemia patients at the American Society of Hematology (ASH) 57th Annual Meeting in Orlando, Florida.
The Company presents an update on its fully enrolled ongoing open label Phase II clinical trial (NCT01794299/EudraCT 2012-004461-41) with its lead product ATIR101™ added as a donor lymphocyte infusion to a haploidentical T-cell depleted stem cell transplantation.
Data presented in Session 732 (Clinical Allogeneic Transplantation) have a cut off date of November 23, 2015. As per that date a statistically significant reduction in Transplant Related Mortality (TRM) and a statistically significant increase in Overall Survival (OS) is observed in comparison to a historical control group based on Kaplan-Meier estimates (p=0.002 and p=0.0006 respectively).
Study details
Twenty-three leukaemia patients with a median age of 41 years (range 21 – 64) have been enrolled into this trial from sites in Canada, Belgium, Germany and the UK. Patients were eligible for an allogeneic hematopoietic stem cell transplantation (HSCT) but could not find a matching donor in time. Seventeen patients had acute myeloid leukaemia (AML) and 6 had acute lymphoblastic leukaemia (ALL). All patients were either in first or second complete remission at the time of HSCT. Myeloablative conditioning regimens were used and (haploidentical) donor grafts were depleted of T-cells (CD34+ selection) prior to transplantation. All patients engrafted rapidly (median 12 days) and subsequently ATIR101™ was infused at a fixed dose of 2×106 CD3+ cells/kg at a median of 28 days post-transplant.
On November 23, 2015 the median follow-up was 292 days post-HSCT. A total of 19 of the 23 patients were beyond 6 months post-HSCT, of which 15 were still alive at that time, and 15 patients were already 12 months post-HSCT, of which 10 were still alive.
No patients (0/23) developed grade III-IV acute Graft-versus-Host-Disease (GVHD) upon infusion of ATIR101™, confirming the efficacy of the elimination of allo-reactive T-cells from ATIR101™. Two cases of grade II acute GVHD were reported with a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post ATIR101™ infusion) respectively.
The primary endpoint of the trial is TRM within 6 months post-HSCT. To date 3 cases of TRM have been reported within the first 6 months post-HSCT. In all cases the cause of death was an infection.
When compared to a historic control group (N=35) consisting of patients who underwent a similar HSCT procedure but without the addition of ATIR101™, TRM was significantly lower (p=0.002) in patients given ATIR101™ after a T-cell depleted haploidentical transplantation. Based on Kaplan-Meier estimates, the 6-month TRM for HSCT + ATIR101™ is 15% versus 37% for HSCT only.
Disease relapse in the trial is limited, with only one patient dying as a result of disease relapse. Combined with the reduced rate of TRM this translates into a significantly improved Overall Survival (p=0.0006) of patients undergoing HSCT + ATIR101™ compared to patients only undergoing HSCT. Based on the Kaplan-Meier estimates, the 1-year survival in the HSCT + ATIR101™ group is 75% compared to only 20% in the historic control group.
Full read out of the data for the primary endpoint will be done at the end of Q1, 2016, when the last patient has reached the 6-month follow up. It is anticipated that the analysis of such data will be reported in April 2016.
Manfred Rüdiger, PhD, Chief Executive Officer of Kiadis Pharma, commented: “We are very excited and enthusiastic about the data from our Phase II trial to date. Compared to previous approaches using T-cell depleted haploidentical HSCT, we have a really strong effect with improved Overall Survival and low Transplant Related Mortality. Infusion of ATIR101™ did not cause life threatening grade III-IV GVHD showing the efficacy of eliminating allo-reactive T-cells. We are now looking forward to initiating our planned Phase III international controlled trial comparing the current Baltimore protocol to our ATIR™ approach. We believe that the very low relapse rates and the absence of grade III-IV GVHD seen in our approach, in which no prophylactic immune-suppression is used, will position ATIR™ very positively for patients.”
strong>Dr. Jeroen< Rovers, Chief Medical Officer of Kiadis Pharma, added: “The data emerging from this Phase II clinical trial provides a very strong signal on the efficacy of ATIR101™ and its capability to reduce life threatening infections, improving overall survival in patients who would otherwise not have a curative treatment option available. It provides a solid basis for discussions with regulatory authorities on potential early market approval.”
Dr. Denis-Claude Roy, Professor of Medicine at the University of Montreal and principal investigator for the study, said: “The data we have seen to date from the various centres involved are highly consistent and fully in line with what we have seen previously in the Phase I trial of ATIR101™ that was done in patients with very poor prognosis. The risk of grade III-IV GVHD seems to be completely mitigated and no immune-suppression is needed with low relapse rates and very good event free survival. These results are similar to those of patients receiving transplants from matched donors.”
