Kiadis Pharma presents pos­i­tive data on the pri­ma­ry end­point of its sin­gle dose Phase II tri­al with ATIR101™

– 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 2×106 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.

Leave a Reply

Your email address will not be published. Required fields are marked *