Effective treatment for rare sight-threatening infection Acanthamoeba keratitis

Press release by Chris Lane UCL

The findings, published in Ophthalmology, describe the efficacy and safety of the first drug candidate for the treatment of Acanthamoeba keratitis (AK), applying a novel and evidence-based treatment protocol.

AK is one type of microbial keratitis (corneal infection) – a condition that results in inflammation of the cornea (the eye’s clear protective outer layer). AK can cause extreme levels of pain as well as light sensitivity.

AK is relatively uncommon, affecting about one in 37,000 contact lens wearers per year in the UK, but it is responsible for about half the cases of sight loss in this group. Contact lens wearers face an increased risk of the disease; a UCL and Moorfields team recently found that people who wear reusable contact lenses face nearly four times the risk of those wearing daily disposables, while showering with lenses in and wearing lenses overnight also each raised the risk by more than threefold.*

The treatment being studied, low concentration polihexanide (PHMB 0.02%), was first compounded and used in the 1990s to treat AK, introduced by a team co-led by this latest study’s lead author, Professor John Dart, and is widely recommended as a treatment for AK, but it is not a licensed drug, and treatment outcomes have been variable.

The Phase 3 randomised controlled double blind clinical trial followed a Phase 1 trial in healthy volunteers which showed that a significantly higher concentration (0.08%) of polihexanide was safe to use. The Phase 3 trial was run in accordance with European Medicines Agency scientific advice and compared the efficacy and safety of a high concentration of polihexanide (0.08%) as a monotherapy to a widely used dual therapy, combining a lower dose of PHMB (0.02%) with propamidine. All trials were sponsored and funded by Italian pharmaceutical company SIFI, with partial co-funding by the European Commission.

The study involved the analysis of 127 people being treated for AK at six hospitals across Europe (in England, Italy and Poland).

The researchers found both formulations to be highly effective when used with the detailed drug delivery protocol, with medical cure rates of 110/127 (87%) overall and for each treatment individually, meaning 87% of people were cured of AK without needing surgery, one of the highest ever reported for AK. The treatment failure rate was 17/127 (13.4%), nearly half of whom required therapeutic corneal transplant surgery. The overall transplant surgery rate of 8/127 (6.3%) is one of the lowest reported in any case series of AK.

The researchers say that the widely recommended dual therapy was more effective than usual in this trial because clinicians were strictly following a set treatment protocol. In addition, the new monotherapy has advantages over dual therapy, as the simplicity reduces the risk of errors in practice.

Dr Vincenzo Papa (Head of Scientific Affairs at SIFI) and co-author of the study said: “This publication in Ophthalmology, the leading peer-reviewed journal in our field, further encourages our continued efforts to make polihexanide 0.08% (Akantior®) available to patients with AK, as the first approved orphan medicinal product. Given the extreme burden of the disease and the high unmet medical need, we are proud of the high efficacy outcomes in the robust setting that the trial created, especially when compared with the efficacy rates of 60% reported with the current best treatment.” 

Based on the comprehensive quality, preclinical and clinical data package generated over 15 years of research, SIFI is now seeking regulatory approvals for polihexanide 0.08% in Europe, the UK and the US.