Hansa Biopharma utvecklar behandlingar för sällsynta immunologiska tillstånd. Imlifidase, som marknadsförs under varumärket IDEFIRIX i Europa, är en antikroppsklyvande enzymterapi som specifikt riktar sig mot och klyver immunoglobulin G (IgG)-antikroppar. Detta möjliggör en snabb reduktion av donatorspecifika antikroppar (DSA) som annars kan orsaka avstötning av transplanterade organ hos högsensitiserade patienter. Terapin har villkorligt marknadsgodkännande i Europa för desensibilisering av vuxna njurtransplantatpatienter med positiv korsreaktion mot en avliden donator.
Högsensitiserade patienter, som utgör cirka 10–15 procent av dem på transplantationsväntelistor i USA och Europa, har höga nivåer av preformade antikroppar mot humana leukocytantigener (HLA), vilket gör det svårt att hitta kompatibla donatororgan. Patienterna riskerar längre väntetider och ökad dödlighet på dialys. Imlifidase erbjuder en möjlighet att genomföra HLA-inkompatibla transplantationer genom att skapa ett tidsfönster där transplantation kan ske innan nya antikroppar bildas, understödda av post-transplantationsimmunsuppression.
Hållbara resultat
De nya långtidsresultaten presenterades av Massimo Mangiola, PhD, från NYU Langone Transplant Institute och belyser imlifidases potential inom njurtransplantation för högsensitiserade patienter. Den förlängda analysen, som bygger på den internationella långtidsuppföljningsstudien 17-HMedIdeS-14, visar på hållbara resultat för högsensitiserade patienter som genomgått njurtransplantation efter desensibilisering med imlifidase. Efter fem år var patientöverlevnaden 90 procent, med tre dödsfall rapporterade mellan sex månader och ett år, och ingen ytterligare död mellan ett och fem år. Transplantatöverlevnaden (dödsjusterad) var 82 procent, i linje med resultaten vid tre år.
Vidare uppvisade patienterna en genomsnittlig njurfunktion, mätt som estimerad glomerulär filtrationshastighet (eGFR), på 50 mL/min/m² vid fem år – ett värde inom det förväntade intervallet 40–60 mL/min/1,73 m² för njurtransplantatmottagare tre år efter transplantation, trots en förväntad nedgång vid fem år.
Hitto Kaufmann, Chief R&D Officer på Hansa Biopharma, kommenterade:
– We are very pleased to see that the 17-HMedIdeS-14 extended pooled analysis data continue to excite the clinical community. This study demonstrated for the first time that HLA-incompatible transplantation following desensitization with imlifidase is a viable option for patients who need it, with long term benefit comparable to standard kidney transplants, providing a life changing alternative to remaining on dialysis.
Bolaget kommenterar
BioStock kontaktade Stephanie Kenney, VP Global Corporate Affairs, för att får veta mer om resultaten.
Can you explain what a 90 per cent patient survival rate and an 82 per cent graft survival rate after five years mean for highly sensitised patients compared to standard kidney transplant outcomes? How does this position imlifidase relative to other desensitisation methods?
– Despite the high-risk immunological profile of these patients, the data demonstrate stable long-term outcomes both on graft survival and patient survival, no different from what is otherwise seen in compatible kidney transplantation.
– We believe the data further supports the clinical benefit of enabling HLA-incompatible kidney transplantation with imlifidase and confirm the case for HLA-incompatible transplantation following desensitisation with imlifidase.
What are your thoughts on the eGFR value of 50 mL/min/m² remaining stable at five years compared to three-year data, and what does this indicate about imlifidase’s long-term impact on kidney function?
– eGFR is a measure of how well the kidneys are working in the body – the higher eGFR indicates better kidney function. According to published data, many kidney transplant recipients three years post-transplant have a mean eGFR between 40-60 ml/min per 1.73 m2 with continued decline of eGFR function at five years post-transplant.
– The stable eGFR seen from three to five years in this long-term analysis reflects good graft function, the absence of significant rejection or chronic injury to the kidney and indicates the absence of worsening overall health.
– We believe this data underscore the potential for imlifidase as a paradigm-shifting treatment in kidney transplantation – one that positively impacts patient outcomes and ensure that highly sensitised kidney transplant patients have access to transplantation.
Can you provide more details about the patient population in the 17-HMedIdeS-14 study, particularly regarding their immunological profile and how representative they are of highly sensitised patients in general?
– The 17-HMedIdeS-14 study included patients who consented to long-term follow-up and were previously enrolled in the phase II imlifidase studies – 13-HMedIdeS-02, 13-HMedIdeS-03, 14-HMedIdeS-04 and 15-HMedIdeS-06.
– The patient population across all four phase II studies consisted primarily of highly sensitised kidney transplant patients with chronic kidney disease, with those included in the pooled analysis representing the most sensitised group, having a median cPRA greater than 99 per cent. These patients are characterised by having pre-formed antibodies (donor specific antibodies or DSAs) that would make it difficult for them to receive a compatible organ for kidney transplantation.
How were potential confounding factors, such as immunosuppressive treatment, handled in the analysis of long-term outcomes in the extended pooled analysis?
– It’s important to know this is real-world data and physicians follow established protocols when managing autoimmune related events – a variety of options exist depending on the specific situation. Hence, no specific or different approach was taken in this study.
