SIFI, an ophthalmic company headquartered in Italy, reported the presentation of positive results from the positive Phase 3 Study [NCT03274895] of AKANTIOR (polihexanide 0.8mg/ml), an investigational anti-amoebic polymer, an orphan drug, for the treatment of acanthamoeba keratitis (AK).
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The Company also reported new data of an indirect comparison of the Phase 3 Trial with the comparable Retrospective Study.
The results were presented by Professor John Dart, the Principal Investigator of the Phase 3 trial for AKANTIOR, at the American Academy of Ophthalmology (AAO) Annual Meeting 2022 (Jones-Smolin lecture), which occurred on October 2, 2022, in Chicago. The Company previously announced positive top-line results from the Phase 3 Trial in October 2021 after more than 15 years of research & development efforts.
The 135-patient randomised, assessor-masked, active-controlled, multiple-centre pivotal Phase 3 Trial showed 84.8% of patients on AKANTIOR reached a clinical resolution of acanthamoeba keratitis and associated inflammation (medical cure) within a median of 4 months of treatment vs 88.5% of the control arm of an unlicensed combination of PHMB 0.2mg/ml + propamidine 1.0mg/ml reaching the pre-defined non-inferiority primary endpoint.
The new analysis presented at the AAO showed that when corrected for risk and other potentially confounding factors – including the stage of the disease at baseline, delay in diagnosis, prior-corticosteroid use and others – the clinical resolution rate increased to 86.7% in the AKANTIOR arm.
This compares to cure rates with unlicensed therapies of 55% as reported in a subgroup of the 227-patient real-world Retrospective Study (Papa V. British Journal of Ophthalmology 2020) of treatment protocols used in clinical practice today.
Additionally, with the AKANTIOR protocol, 62% of patients achieved full visual acuity restoration compared to 28% with the treatment protocols used in the Retrospective Study. Similarly, the proportion of patients ending up with poor visual acuity of BCVA of less than 6/18 were decreased from 47% in the Retrospective Study to 19% with the AKANTIOR protocol.
Only 3% patients (2 out 66) receiving AKANTIOR required cornea transplant in the Phase III Trial, which increased to 7.6% (5 out 66) after leaving the trial. This compares to 25% or more as reported in the recent published literature.
The safety and tolerability profile was similar to what was seen in the previously reported Phase 1 results on healthy volunteers as well as in extensive pre-clinical and toxicology studies with only 1 patient on AKANTIOR failing treatment because of toxicity.
John Dart, Professor at the University College London Institute of Ophthalmology said "The medical cure rate of 86.7% for AKANTIOR in our Phase 3 Trial was similar for the widely used, dual agent, control treatment of PHMB 0.2mg/ml and propamidine 1.0 mg/ml. These results are better than we had anticipated and amongst the best reported.
"We have shown that much of this improvement is the result of the detailed delivery protocol, developed and evaluated by the 6 European study centres, and which is now available to clinicians. Unlike the control treatments, AKANTIOR is a monotherapy which has been through extensive safety, stability, and efficacy tests.
"As monotherapy it is both easier to use and, if licensed as we expect, will become widely available unlike current therapies which have to be manufactured by compounding pharmacies resulting in frequent treatment delays."
Based on these and full study results, the Company currently plans to file New Drug Application (NDA) with U.S. Food and Drug Administration (FDA) in 2023, which is consistent with previous guidance.
Further, as previously announced, the European Medicines Agency (EMA) validated the Company's Marketing Authorization Application (MAA) for AKANTIOR in May 2022. Accordingly, the Company maintains its guidance of expecting full regulatory approval by the European Commission mid-2023.
In the meantime the Company make AKANTIORÃ’ available for patients within the Early Access Program (EAP) currently running in several European countries
SIFI is evaluating different options for the commercialization of AKANTIOR globally, including potential out-license agreements outside its core markets.
ABOUT Phase 3 TRIAL:
This was a randomized, assessor-masked, active-controlled, multiple-centre pivotal Phase 3 Trial designed to evaluate the efficacy, safety and tolerability of AKANTIOR compared to a control arm of an unlicensed combination of polihexanide 0.2mg/ml + propamidine 1.0mg/ml for the treatment of acanthamoeba keratitis [NCT03274895].
Both treatment arms used a standardized, day-only treatment protocol. The primary endpoint was defined as the 'clinical resolution rate over a 12-month timeframe', based on the percentage of patients cured following 30 days after the discontinuance of all study therapies and within 12 months of randomization.
135 patients were randomized in the trial, of which 69 were randomized into the treatment arm and the remaining 66 into the control arm.
The average age of the patients was 36.5 years old (ranging from 15–73); 58.2% of the patients were female. 127 patients received a study drug and had its diagnosis confirmed via independent laboratory and constitute the Intention-To-Treat (ITT) population.
ABOUT Acanthamoeba Keratitis (AK):
AK is a rare, severe, life-changing progressive parasitic corneal infection caused by Acanthamoeba, a free-living amoeba. Urgent medical intervention is required to save the patient's sight. The disease has shown resistance, leads to poor vision, blindness, or even eye loss and often requires single or multiple corneal transplant procedures.
It affects people of all ages, most of whom are young or middle-aged soft contact lens wearers.
Patients report unbearable pain and extreme light sensitivity and can rarely work or lead normal lives until symptoms resolve. The incidence of acanthamoeba keratitis has been rapidly growing in recent years. ■