- 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).
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.”
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.”
For patients suffering from blood cancers, an allogeneic hematopoietic stem cell transplantation (HSCT) is generally regarded as the most effective curative approach. During an HSCT treatment, the bone marrow, harbouring the diseased cancer cells, is completely destroyed and subsequently replaced by stem cells in the graft from a healthy donor. After an HSCT treatment it usually takes the patient at least six to twelve months to recover to near-normal blood cell levels and immune cell functions. During this period, the patient is highly vulnerable to infections caused by bacteria, viruses and fungi but also to disease relapse.
ATIR101™ (Allodepleted T-cell ImmunotheRapeutics) provides for a safe donor lymphocyte infusion (DLI) from a partially matched (haploidentical) family member without the risk of causing severe Graft-versus-Host-Disease (GVHD). The T-cells in ATIR101™ will help fight infections and remaining tumour cells and thereby bridge the time until the immune system has fully re-grown from stem cells in the transplanted graft.
In ATIR101™, T-cells that would cause GVHD are eliminated from the donor lymphocytes using Kiadis Pharma’s photodepletion technology, minimising the risk of GVHD and eliminating the need for prophylactic immune-suppression. At the same time, ATIR101™ contains potential cancer killing T-cells from the donor that could eliminate residual cancer cells and help prevent relapse of the disease, known as the Graft-versus-Leukaemia (GVL) effect.
Therefore, ATIR101™, administered as an adjunctive immuno-therapeutic on top of HSCT, provides the patient with functional, mature immune cells from a partially matched family donor that can fight infections and tumour cells but that do not cause GVHD. ATIR101™ thus has the potential to make curative HSCT a viable option to many more patients.
The Company estimates that approximately 35% of patients who are eligible and in urgent need of HSCT will not find a matching donor in time. A partially matched (haploidentical) family donor, however, will be available to over 95% of patients.
ATIR101™ consisting of donor T-cells that fight infections and residual tumour cells while not eliciting severe GVHD, is designed to result in low relapse rates and low rates of death due to infections, in the absence of severe acute GVHD.
About Kiadis Pharma
Kiadis Pharma is a clinical stage biopharmaceutical company focused on research, development and future commercialisation of cell-based immunotherapy products for the treatment of blood cancers and inherited blood disorders. The Company believes that its innovative products have the potential to address the current risks and limitations connected with allogeneic hematopoietic stem cell transplantation (HSCT), being graft-versus-host-disease (GVHD), cancer relapse, opportunistic infections and limited matched donor availability. HSCT is generally regarded as the most effective curative approach to blood cancers and certain inherited blood disorders and the Company expects that HSCT could become a first-choice treatment for blood cancers and inherited blood disorders once current risks and limitations are addressed, thereby meeting a significant unmet medical need with its products.
Currently, the Company’s product ATIR101™ is being tested using a single dose regimen in an open-label Phase II trial in patients with blood cancer who have not found a matching donor and where a partially matched (haploidentical) family member is used as donor for HSCT. Kiadis Pharma announced full enrolment of this trial in July 2015. The primary endpoint for the last patient in this trial will be reached at the end of Q1, 2016, top-line results to follow at the beginning of Q2, 2016.
In addition, the Company is enrolling blood cancer patients in a further Phase II clinical trial to study the safety and efficacy of administrating a second dose of ATIR101™ to further improve the HSCT outcome.
The European Medicines Agency (EMA) has issued an Advanced Therapy Medicinal Product (ATMP) certificate for manufacturing quality and non-clinical data to the Company, and to date Kiadis Pharma is one of only five companies that have received such a certificate.
ATIR101™ has been granted Orphan Drug Designations both in the US and Europe.
Kiadis Pharma is based in Amsterdam, the Netherlands and its shares are listed on Euronext Amsterdam and Euronext Brussels.
For more information, please contact:
Manfred Rüdiger, CEO
1114 AA Amsterdam-Duivendrecht
Tel. +31 20 314 02 50
International Media and Investor Contact:
Mary-Jane Elliott, Lindsey Neville, Hendrik Thys
Consilium Strategic Communications
Tel: +44 (0) 203 709 5708
Forward Looking Statements
Certain statements, beliefs and opinions in this press release are forward-looking, which reflect Kiadis Pharma’s or, as appropriate, Kiadis Pharma’s directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, Kiadis Pharma expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither Kiadis Pharma nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.