- 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™
- Initiation of a randomised Phase III trial in the second half of 2016 ~
-
Management will host a webcast to discuss the data today at 18.00 CET ~
Amsterdam, The Netherlands, April 4, 2016, – 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 positive results on the primary endpoint of its
single dose Phase II trial (NCT01794299/EudraCT 2012-004461-41) with its lead product
ATIR101™ at the 42nd Annual Meeting of the European Society of Blood and Marrow
Transplantation (EBMT) in Valencia, Spain.
The data presented in session O042 by Dr. Denis-Claude Roy, Professor of Medicine at the
University of Montreal and the principal investigator for the trial, confirms that ATIR101™ can
be safely infused, does not cause grade III-IV Graft-versus-Host-Disease (GVHD) and shows a
significant reduction in Transplant Related Mortality (TRM) and a significant improvement in
Overall Survival (OS) in comparison to a historical control group of patients undergoing a T-cell
depleted haploidentical donor transplantation only.
Trial details
Twenty-three leukaemia patients with a median age of 41 years (range 21-64) were enrolled
into and treated on this trial from sites in Canada, Belgium, Germany and the United Kingdom.
Patients were eligible for an allogeneic hematopoietic stem cell transplantation (HSCT) but
could not find a matching donor in time. Sixteen patients had acute myeloid leukaemia (AML)
and seven had acute lymphoblastic leukaemia (ALL). Patients were either in first or second
complete remission at the time of the HSCT and the majority of patients (57%) had a poor
prognosis based on their disease risk index and cytogenetic profile. A myeloablative
conditioning regimen was used and (haploidentical) donor grafts were depleted of T-cells
(CD34+ selection) prior to transplantation. Patients engrafted rapidly (median 12 days) and
ATIR101™ was subsequently infused at a fixed dose of 2x106 CD3+ cells/kg at a median of 28
days post-transplant.
The median follow-up, on March 24, 2016, was 414 days (range 110 – 742) post-HSCT, at
which point all patients were beyond six months post-HSCT, allowing assessment of the
primary endpoint of this trial, which is TRM at six months. Patients will be continued to be
followed in order to collect further long-term outcome data.
No patients (0/23) developed grade III-IV GVHD upon infusion of ATIR101™, confirming the
efficacy of the elimination of allo-reactive T-cells from ATIR101™. Three cases of grade II acute
GVHD were reported; one case developed before ATIR101™ infusion and the other two cases
had a delayed onset, at day 173 and day 247 post-HSCT (145 and 219 days post ATIR101™
infusion) respectively. In the patient who developed GVHD before ATIR101™ infusion, GVHD
resolved quickly and subsequently ATIR101™ was infused, not triggering any further GVHD.
The primary endpoint of the trial is TRM within six months post-HSCT. Overall, three cases of
TRM were reported within the first six months post-HSCT, giving a TRM rate of 13%. In all
cases the cause of death was an infection. No mortality was observed within the first 100 days
post-HSCT. In addition to the three TRM cases, only one patient died as a result of disease
relapse within the first six months, resulting in an Overall Survival of 83%.
When compared to a historic control group (N=35) consisting of patients matching the
inclusion and exclusion criteria of the Company’s Phase II trial who underwent a similar HSCT
procedure from haploidentical family members but without the addition of ATIR101™, TRM
was significantly lower (p=0.005) in patients who were given ATIR101™ after a T-cell depleted
haploidentical transplantation. The six month TRM for HSCT + ATIR101™ is 13% versus 37% for
HSCT only.
Disease relapse in the trial was limited, with only two patients developing disease relapse
within the first 12 months after HSCT (at day 61 and 90 post HSCT respectively). Combined
with the reduced rate of TRM, this translates into a significantly improved OS (p=0.0026) of
patients undergoing HSCT + ATIR101™ compared to patients undergoing HSCT only. Based on
the Kaplan-Meier estimates, the one-year survival in the HSCT + ATIR101™ group was 64%
compared to only 20% in the historic control group.
Based on the positive results from this Phase II trial, the Company will proceed with the
development of ATIR101™ as an adjunctive immuno-therapeutic treatment to a haploidentical
HSCT for patients with acute leukaemia, initiating a randomised Phase III trial in the second
half of 2016. In addition, the Company will discuss the opportunity for potential conditional
(accelerated) approval of ATIR101™ with the regulatory authorities.
Manfred Rüdiger, PhD, Chief Executive Officer of Kiadis Pharma, commented: “We are very
excited about the strong and compelling results from our Phase II trial. The data shows
substantially improved Overall Survival rates and low Transplant Related Mortality. In
addition, with the infusion of ATIR101™, no incidents of life threatening grade III-IV GVHD
were detected, despite patients not receiving any prophylactic immune-suppressants. We
believe that our ATIR101™ approach compares very favourably with the post-transplant
cyclophosphamide protocols pioneered in Baltimore. Having no grade III-IV GVHD and very low
relapse rates makes us believe that ATIR™ will become an attractive alternative for patients
who don’t have a matching donor. We are looking forward to the initiation of the randomised
Phase III international controlled trial, comparing our ATIR101™ approach directly to the
Baltimore approach. The data also provides a solid base for discussions with regulatory
authorities concerning potential early market approval of ATIR101™.”
Dr. Denis-Claude Roy, Professor of Medicine at the University of Montreal and one of the
principal investigators for the trial, added: “With this latest data we can confirm the safety
of ATIR101™, without any incidents of grade III-IV GVHD, significant reduction in Transplant
Related Mortality, low relapse rates and very good event free survival, which we believe
confirms the efficiency of photodepletion-based elimination of allo-reactive T-cells. Indeed,
the data of patients receiving transplants with a haploidentical donor and an ATIR101™
infusion are very similar to those from patients with a matched donor. As a doctor, I am very
excited about this development and its potential to change patient fates.”
Webcast
Manfred Rüdiger, Chief Executive Officer and Jeroen Rovers, Chief Medical Officer, together
with Dr. Denis-Claude Roy, Professor of Medicine at the University of Montreal and principal
investigator for the trial, will host a webcast to discuss the data today at 18.00 CET.
To register for the webcast, please visit the homepage of Kiadis Pharma at: www.kiadis.com.
To listen to the webcast, please call the appropriate number below, 10 minutes prior to the
start time:
The Netherlands: 020 716 8427
Toll-free The Netherlands: 0800 265 8619
Belgium: 02 401 2722
Toll-free Belgium: 0800 50 562
United Kingdom: 0203 139 4830
Toll-free United Kingdom: 0808 23 700 30
United States: 1718 873 9077
Toll-free United States: 1866 928 7517
Conference ID: 25282024#
The webcast will be conducted in English and viewers will have the opportunity to submit
questions during the Q&A portion of the live webcast. A replay of the webcast will be made
available on Kiadis Pharma’s website.
About ATIR101™
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 nearnormal
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, minimizing 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 commercialization 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.
The Company’s product ATIR101™ is being tested using a single-dose regimen in an open-label
fully enrolled 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. The primary endpoint for the final patient in this trial will be reached at the end of Q1,
2016 and top-line results will be announced in April 2016. Very encouraging and positive
interim data of this trial was presented recently at ASH2015.
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.
ATIR201™ will be developed for inherited blood disorders with an initial focus on
thalassaemia, an inherited blood disorder which results in improper oxygen transport and
destruction of red blood cells in a patient. ATIR201™ is expected to enter Phase I/II clinical
development for thalassaemia in the first quarter of 2016. Kiadis Pharma recently announced
a collaboration with the Thalassaemia International Federation (TIF), an internationally
renowned organisation that seeks to address the needs of patients, carers, healthcare
professionals and the general public in the area of thalassaemia.
Kiadis Pharma is based in Amsterdam, the Netherlands and its shares are listed on Euronext
Amsterdam and Euronext Brussels. Further information can be found at: www.kiadis.com
Company Contact:
Manfred Rüdiger, CEO
Kiadis Pharma
Entrada 231-234
1114 AA Amsterdam-Duivendrecht
The Netherlands
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.
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