Polihexanid (1) – Akantior®

• Clinical trials
  • Study 043/SI was a randomised, double-blind Phase III trial investigating the efficacy, safety and tolerability of polyhexanide (0.8 mg/ml) compared with polyhexanide (0.2 mg/ml) and propamidine (1 mg/ml) as combination therapy in people with Acanthamoeba keratitis.

Patients aged 12 years and over with Acanthamoeba keratitis

• For patients aged 12 years and over with Acanthamoeba keratitis, there is a hint of a non-quantifiable additional benefit for polyhexanide, as the scientific evidence does not permit quantification.
• The certainty of the evidence is assessed as a hint in light of the uncontrolled results and the possibility of outcome-biased reporting.
• mortality
  • Overall mortality was recorded as part of the safety survey. No deaths occurred in study 043/SI.
• Morbidity – rate of clinical cure
  • In study 043/SI, the ‘rate of clinical cure within 12 months’ was defined as the primary endpoint as follows: the proportion of participants who were cured 30 days after discontinuation of all study treatments, within 12 months of study enrolment.
  • A participant was classified as cured if the disappearance or absence of all the following clinical signs was confirmed by a slit-lamp examination carried out by the study staff: • No corneal inflammation requiring treatment (including subepithelial infiltrates, stromal infiltrates and oedema) with a healed corneal epithelium and minimal punctate discolouration (10 points or fewer, corresponding to Grade 1 on the Oxford scale) • No or mild conjunctivitis (including bulbar injection, bulbar oedema, tarsal hyperaemia): mild conjunctivitis is acceptable if it is associated with other concurrent conditions such as blepharitis. • No limbitis, scleritis or inflammation of the anterior chamber. • No recurrence within 30 days of discontinuing all topical and systemic treatment for Acanthamoeba keratitis.
  • Against the backdrop of the curative therapeutic approach, the proportion of patients who achieve a cure for Acanthamoeba keratitis is considered clinically relevant.
  • However, the present operationalisation of the composite endpoint reflects only one aspect of clinical cure, i.e. essentially eradication in association with the clinical resolution of inflammation and healing of the corneal epithelium, corresponding to a clinical response rate.
  • In the present analysis, only data from individuals with confirmed Acanthamoeba keratitis were included (‘Efficacy Population’; n = 66). Analyses incorporating the intention-to-treat (ITT) population (n = 69) are not available.
  • In the intervention arm of study 043/SI, the ‘clinical cure rate’ was 84.8%.
  • Overall, based on the current operationalisation of the endpoint ‘clinical cure rate within 12 months’, no conclusion can be drawn regarding the extent of the additional benefit. The endpoint is therefore presented only as supplementary information.
• quality of life
  • In study 043/SI, the ‘Visual Function Questionnaire-25’ (VFQ-25) was used to assess the impact of potential corneal events on function and health-related quality of life.
  • The VFQ-25 is a self-assessment questionnaire on vision-related quality of life, comprising a total of 26 items and 12 subscales. Of these, 25 items (11 subscales) assess visual function and 1 item (1 subscale) assesses general health.
  • As no MMRM or responder analyses, nor any analyses of the ITT population, were presented, the resolution presents the change in the mean score from baseline to the end of the study for the efficacy population.
  • At baseline, the mean score on the VFQ-25 total scale was 64.9 points and improved by 23.5 points by the end of the study.
  • However, due to the lack of a comparison, no conclusion can be drawn regarding the extent of the additional benefit for health-related quality of life.
• Side effects
  • In study 043/SI, adverse events (AEs) were recorded up to the end of the study for each participant. The median duration of treatment was 120 days (min.: 10; max.: 387). The analysis of AEs was carried out without taking into account events related to the participants’ underlying conditions.
  • AEs occurred in 45% of patients in the intervention arm. The results are presented here for supplementary information only. A severe AE (CTCAE grade ≥ 3) occurred in 6% of study participants in the intervention arm, and no serious AEs were reported. In total, 10% of the ITT population withdrew from the study due to an AE.
  • Due to the single-arm nature of the data, it is not possible to assess the extent of the additional benefit for the ‘side effects’ category.
• Overall assessment
  • This benefit assessment is based on the data supporting marketing authorisation from the intervention arm of the blinded, controlled, multicentre Phase III study 043/SI. The comparative data from this study do not provide any additional information for assessing the additional benefit.
  • Results are available on mortality, health status, health-related quality of life and side effects. However, due to the lack of a comparator, it is not possible to quantify the extent of the additional benefit on the basis of these data.
  • The indirect comparison presented in the dossier for the endpoint ‘clinical cure rate within 12 months’ is not used for the present benefit assessment. The main reason for this is that, based on the available data, it cannot be assumed that the study population and the control population used are sufficiently similar. In particular, the comparison arm lacks key information on disease severity at the start of treatment and other baseline characteristics, the observation period, the propensity score model used, and the operationalisation of the measured endpoint. Furthermore, the lack of temporal parallelism also represents a further critical aspect.
  • Overall, a non-quantifiable additional benefit is inferred for polyhexanide, as the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.