Imlifidase (1) – Idefirix®

• Clinical trials
  • The S-02 trial is an open-label, non-randomised Phase II trial designed to assess the safety, tolerability, pharmacokinetics and efficacy of imlifidase.
  • Study S-03 is an open-label, non-randomised Phase II study designed to investigate the safety, tolerability, efficacy and pharmacokinetics of imlifidase (0.25 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg).
  • Study S-04 was an open-label, non-randomised Phase I/II study designed to investigate the safety and tolerability of imlifidase (0.24 mg/kg intravenously as a single dose) and to eliminate donor-specific HLA antibodies (DSAs) and prevent antibody-mediated rejection following transplantation in individuals with high levels of HLA immunisation.
  • Study S-06 was an open-label, non-randomised Phase II study to evaluate the efficacy of imlifidase (0.25 mg/kg administered as a single dose or repeated at a later date) for the desensitisation of transplant patients with a positive cross-match test who have access to a living donor or a deceased donor organ.
  • Study S-14 is a long-term follow-up study of studies S-02, S-03, S-04 and S-06.
  • Study S-13 is a retrospective study designed to collect additional donor and recipient data from individuals who were treated with imlifidase prior to kidney transplantation in studies S-02 and S-03.

Adult kidney transplant patients who have antibodies resulting in a positive cross-match against an available deceased donor.

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• Consequently, the G-BA classifies the extent of the additional benefit of imlifidase for the desensitisation treatment of adult kidney transplant patients who possess antibodies that result in a positive cross-match against an available deceased donor, as non-quantifiable on the basis of the limited data available, in accordance with the criteria set out in Section 5(7) of the AM-NutzenV.
• An additional benefit exists in accordance with Section 35a(1), sentence 11, first half-sentence, of SGB V, but is non-quantifiable because the scientific evidence does not permit this.
• mortality
  • In studies S-03, S-04 and S-06, and for participants in the follow-up study S-14 of the precursor studies S-04 (after 2 years) and S-06 (after 3 years), no deaths occurred in any of these cases.
  • Among individuals who did not actively participate in study S-14, there was one death each for the predecessor studies S-04 and S-06.
  • Overall, based on the results of studies S-03, S-04, S-06 and S-14, no conclusion can be drawn regarding the extent of the additional benefit for the endpoint category of mortality.
• Morbidity – Graft survival
  • The endpoint of graft survival is patient-relevant.
  • Graft survival was assessed in studies S-03, S-13, S-04, S-06 and S-14.
  • One person in study S-04 and two people in study S-06 experienced graft loss.
  • In study S-13, no graft loss was observed for study S-03.
  • In the follow-up study S-14, no graft loss was observed in study participants following administration of imlifidase.
  • For individuals who did not actively participate in study S-14 (after the end of the predecessor study and prior to enrolment in study S-14), a total of three graft losses were observed in the predecessor study S-04.
• Quality of life – Kidney Disease Quality of Life Questionnaire – short form (KDQOL-SF)
  • Quality of life was assessed using the KDQOL-SF only in the follow-up study S-14 at years 1, 2, 3 and 5 after transplantation.
  • In studies S-03, S-04 and S-06, patients’ quality of life was not assessed using the KDQOL-SF.
  • Consequently, no baseline values are available, which is why a descriptive pre-post comparison with the baseline value is not possible for the single-arm studies.
  • Consequently, no data suitable for benefit assessment were presented in the quality of life category.
• Side effects
  • Serious adverse events (SAEs) were observed in 3 out of 5 participants in study S-03, in 11 out of 17 participants in study S-04, and in 15 out of 19 participants in study S-06.
  • Severe adverse events (AEs, CTCAE grade ≥ 3) occurred during treatment with imlifidase in 4 out of 17 participants in study S-04 and in 18 out of 19 participants in study S-06.
  • In study S-06, one participant discontinued treatment due to an AE within 30 days of receiving imlifidase.
  • No safety data were submitted by the pharmaceutical manufacturer for the follow-up study S-14.
  • AE of particular interest in study S-04 included ‘infections’ and ‘infusion-related reactions’.
  • In the S-04 study, 35.3% of participants developed infections within 30 days of receiving imlifidase.
  • No infections were observed between 30 days after administration of imlifidase and the follow-up visit.
  • No participants in Study S-04 experienced infusion-related reactions.
  • Overall, based on the results of studies S-03, S-04 and S-06, no conclusion can be drawn regarding the extent of the additional benefit for the endpoint category ‘side effects’.
• Overall assessment
  • The following single-arm studies, which formed the basis for marketing authorisation, were used to assess the additional benefit of imlifidase for the desensitisation treatment of adult kidney transplant patients who possess antibodies resulting in a positive cross-match against an available deceased donor: S-03, S-04, S-06 and S-13, S-14 (follow-up study).
  • Results are available from studies S-03, S-04, S-06, S-13 and S-14 on patient-relevant endpoints in the categories of mortality, morbidity, quality of life and side effects.
  • Adults who require a kidney transplant due to their condition, but who have antibodies that result in a positive cross-match against an available deceased donor, are generally severe or impossible to transplant under current organ allocation guidelines using the desensitisation treatment currently available.
  • Imlifidase is intended to enable transplantation for these individuals by destroying the HLA antibodies.
  • However, a comparative assessment of the study results is not possible due to the single-arm design of studies S-03, S-04, S-06, S-13 and S-14.
  • Consequently, it is not possible to quantify the additional benefit on the basis of the data provided.
  • Overall, a non-quantifiable additional benefit remains, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.