Study zeroes in on treatment for rare sight-threatening infection

AK is one type of microbial keratitis. AK can cause extreme levels of pain as well as light sensitivity and vision loss. (Image courtesy of Adobe Stock)

Scientists at University College London (UCL) and Moorefields Eye Hospital has developed a drug candidate found to be highly effective in treating a rare sight-threatening eye infection in a new international clinical trial.

The findings, published in Ophthalmology,² detail the efficacy and safety of the first drug candidate for the treatment of Acanthamoeba keratitis (AK), applying a novel and evidence-based treatment protocol.

According to a news release from UCL,¹ AK is one type of microbial keratitis (corneal infection). AK can cause extreme levels of pain as well as light sensitivity.

AK causes the front surface of the eye, the cornea, to become painful and inflamed, due to infection by Acanthamoeba, a cyst-forming microorganism. The Moorfields Eye Hospital NHS Foundation Trust indicated the most severely affected patients (a quarter of the total) end up with less than 25% of vision or become blind following the disease and face prolonged treatment. Overall, 25% of people affected require corneal transplants to treat the disease or restore vision.³

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.

Contact lens use is now the leading cause of microbial keratitis in patients with otherwise healthy eyes in countries in the global north. Sight loss resulting from microbial keratitis is uncommon but Acanthamoeba, although a rare cause, is one of the most severe and is responsible for about half of those contact lens users who develop sight loss after keratitis.

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, John Dart, MD, and is widely recommended as a treatment for AK, but it is not a licensed drug, and treatment outcomes have been variable.

Dart, a processor at UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust, pointed out acanthamoeba keratitis in contact lens users can be prevented by following a few key points.

“Do use daily disposables if possible, wash and dry hands before handling lenses, maintain good lens and lens case hygiene, and don’t use them when bathing swimming or showering, or use goggles and renew the lens after use, don't wear them overnight, and don’t use them every day,” he said.

Moreover, Dart noted that when the disease does develop the course is prolonged and, in the recent past, one third of patients have had poor visual outcomes with one quarter requiring surgery at some stage.

“PHMB 0.02% is an effective and widely recommended unlicensed therapy, but many clinicians have trouble accessing it, mistakes in formulation can sometimes lead to poor results, and the lack of a proven treatment protocol has resulted in wide variations in how the drug is used and in treatment outcomes,” Dart said. “We hope that our new robust findings with polihexanide 0.08% will be a game changer for AK treatment, by improving access and the consistency of treatment, addressing currently unmet patient needs.”

The Phase 3 randomized 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.¹

The study involved the analysis of 127 people being treated for AK at six hospitals across Europe (in England, Italy and Poland).²

According to the UCL news release, the scientists 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.²

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.

Vincenzo Papa, MD, PhD, head of Scientific Affairs at SIFI and co-author of the study, pointed out in the UCL news release the release of the study 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,” Papa said in the news release.

According to UCL, based on the 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 United States.¹

References

1 Effective treatment for rare sight-threating infection. EurekAlert! Accessed October 30, 2023. https://www.eurekalert.org/news-releases/1006000

2 Dart JKG, Papa V, Rama P, Knutsson KA, Ahmad S, Hau S, Sanchez S, Franch A, Birattari F, Leon P, Fasolo A, Mrukwa Kominek E, Jadczyk-Sorek K, Carley F, Hossain P, Minassian DC, TEMPORARY REMOVAL: <The Orphan Drug for Acanthamoeba Keratitis (ODAK) trial: PHMB (polihexanide) 0.08% and placebo versus PHMB 0.02% and propamidine 0.1% >, Ophthalmology (2023), doi: https://doi.org/10.1016/j.ophtha.2023.09.031

3 Acanthamoeba keratitis | Moorfields Eye Hospital NHS Foundation Trust. Accessed October 30, 2023. https://www.moorfields.nhs.uk/condition/acanthamoeba-keratitis