Acanthamoeba Keratitis

A drug candidate has been found to be highly effective in treating a rare sight-threatening eye infection in a new international clinical trial. A drug candidate, based on pioneering UCL and Moorfields Eye Hospital research and currently under development by SIFI S.p.A., has been found to be highly effective in treating a rare sight-threatening eye infection in a new international clinical trial. 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. Professor John Dart (UCL Institute of Ophthalmology and Moorfields Eye Hospital NHS Foundation Trust) said: "Acanthamoeba keratitis in contact lens users can be prevented by following safe use advice: do use daily disposables if possible, wash and dry hands before handling lenses, maintain good lens and lens case hygiene, and don'tuse 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. "Unfortunately, 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. 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 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. Juliette Vila Sinclair Spence, Rare Disease Patient Advocate & Chairwoman, Acanthamoeba Keratitis Eye Foundation, commented: "Exciting news! AK Warriors (aka patients) are now one step closer to receiving the first-ever product with a standardised protocol for Acanthamoeba keratitis. This is starting to bring light to the end of the tunnel." More about Acanthamoeba keratitis 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 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.** 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. 90% of AK cases are associated with avoidable risks. In recent years a UCL and Moorfields team found AK to be on the rise in South-East England.*** Furthermore, AK is also increasing in prevalence in some part of the global south, including parts of India, where the leading risk factor is agriculture associated corneal trauma. The findings reported here are also relevant to these populations.

Collaboration offers potential access to hundreds of patients across several European Countries. SIFI will focus its European market access and commercial activities on existing markets, and the new markets Germany and the United Kingdom. SIFI expects a potential positive opinion by the Committee for Medicinal Products for Human Use and New Drug Application to the US Food and Drug Administration (FDA) in 2023. CATANIA, Italy, Jan. 10, 2023 /PRNewswire/ -- SIFI, a leading international ophthalmic company headquartered in Italy, today announced that it has partnered with Avanzanite Bioscience (Avanzanite), a Dutch specialty pharmaceutical company, to exclusively commercialize and distribute AKANTIOR® (polihexanide) in 26 Countries within the European Economic Area and Switzerland. Under the terms of the agreement, SIFI will handle all ongoing regulatory activities, whilst Avanzanite will focus on market access, distribution and commercial activities in those markets. The partnership will enable commercial access to AKANTIOR® to an estimated 500 patients who suffer from Acanthamoeba Keratitis (AK) each year in these territories. SIFI will focus and continue to invest in market access and commercial activities related to AKANTIOR® on existing and new European Countries, such as Italy, France, Germany, United Kingdom, Spain, Romania and Turkey, whilst continuing to evaluate different options for the commercialization of AKANTIOR® globally, including potential license agreements outside its core markets. SIFI and Avanzanite also agreed to expand the Early Access Program (EAP) already in place for the big 5 European Countries to selected Countries within the scope of the license to Avanzanite. The European Medicines Agency (EMA) validated SIFI's Marketing Authorization Application (MAA) for AKANTIOR® in May 2022. SIFI expects a potential positive opinion of the EMA Committee for Medicinal Products for Human Use in 2023. Detailed positive results and new data from the completed phase 3 trial were presented at the American Academy of Ophthalmology Annual Meeting in Chicago in October 2022. Fabrizio Chines, SIFI Chairman and CEO, stated "We made significant investments on AKANTIOR® throughout 15 years of rigorous research and are looking for ways to maximize our asset's potential. As we advance towards a regulatory approval in dozens of European Countries, we are excited to partner with Avanzanite, as this collaboration promises to accelerate access to our drug candidate to patients in several markets that are outside of our current commercial focus." Mr. Chines continued, "Avanzanite's management team brings a substantial track record in delivering orphan medicines to niche European markets, which we expect will result in an accelerated return on investment for SIFI." Avanzanite's Founder and CEO, Adam Plich, stated, "Today's announcement bears all the hallmarks of what we're passionate about: Increasing access to orphan drugs for patients suffering from very rare diseases across Europe and optimizing economic returns for our partners. Plain and simple, through this alliance, Avanzanite is not only contributing to market access to those afflicted by the devastation of AK in European markets previously unapproachable to SIFI but is also unlocking additional revenue potential for the Company." ABOUT Acanthamoeba Keratitis (AK): AK is a rare, severe, 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. 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 and it accounts for 50% of blindness among contact lens users. ABOUT AKANTIOR®: AKANTIOR® (polihexanide) is an investigational anti-amoebic polymer that has been granted Orphan Drug Designation by both the European Medicines Agency ("EMA") and Food and Drug Administration ("FDA") for AK. It acts on both the trophozoites and cysts of the protozoan Acanthamoeba. It is formulated at a unique 0.8mg/ml high dose strength which makes it possible to administer as monotherapy eye drops in single-dose containers. Polihexanide is also being developed by SIFI for the treatment of fungal keratitis for which indication it also has FDA Orphan Drug Designation. ABOUT SIFI: SIFI is a leading international ophthalmic company, headquartered in Italy, focusing on eye care since 1935. SIFI develops, manufactures, and markets innovative therapeutic solutions for patients with ophthalmic conditions. SIFI is fully committed through its R&D to improving the quality of life of patients, exporting treatments to more than 25 countries worldwide with a direct presence in Italy, Spain, France, Romania, Mexico, and Turkey. ABOUT AVANZANITE BIOSCIENCE: Avanzanite is a commercial-stage pharmaceutical company, headquartered in the Netherlands, on a mission to redefine the commercialization of orphan medicines to improve patient access across Europe and beyond. Derived from the word 'Tanzanite' – one of the rarest and most underappreciated gemstones on earth – Avanzanite's economic goal is to offer end-to-end commercialization and distribution partnerships to research-based biopharmaceutical originators to unlock the full value of their orphan medicines in European markets. The Company's humanitarian goal stems from their commitment to enabling access to novel medicines for patients who suffer from orphan diseases regardless of where in Europe they may live. Logo - Media Contact: +39 3336999669 [email protected] SOURCE SIFI S.p.A.

Collaboration offers potential access to hundreds of patients across several European Countries. SIFI will focus its European market access and commercial activities on existing markets, and the new markets Germany and the United Kingdom. SIFI expects a potential positive opinion by the Committee for Medicinal Products for Human Use and New Drug Application to the US Food and Drug Administration (FDA) in 2023. CATANIA, Italy, Jan. 10, 2023 /PRNewswire/ -- SIFI, a leading international ophthalmic company headquartered in Italy, today announced that it has partnered with Avanzanite Bioscience (Avanzanite), a Dutch specialty pharmaceutical company, to exclusively commercialize and distribute AKANTIOR® (polihexanide) in 26 Countries within the European Economic Area and Switzerland. Under the terms of the agreement, SIFI will handle all ongoing regulatory activities, whilst Avanzanite will focus on market access, distribution and commercial activities in those markets. The partnership will enable commercial access to AKANTIOR® to an estimated 500 patients who suffer from Acanthamoeba Keratitis (AK) each year in these territories. SIFI will focus and continue to invest in market access and commercial activities related to AKANTIOR® on existing and new European Countries, such as Italy, France, Germany, United Kingdom, Spain, Romania and Turkey, whilst continuing to evaluate different options for the commercialization of AKANTIOR® globally, including potential license agreements outside its core markets. SIFI and Avanzanite also agreed to expand the Early Access Program (EAP) already in place for the big 5 European Countries to selected Countries within the scope of the license to Avanzanite. The European Medicines Agency (EMA) validated SIFI's Marketing Authorization Application (MAA) for AKANTIOR® in May 2022. SIFI expects a potential positive opinion of the EMA Committee for Medicinal Products for Human Use in 2023. Detailed positive results and new data from the completed phase 3 trial were presented at the American Academy of Ophthalmology Annual Meeting in Chicago in October 2022. Fabrizio Chines, SIFI Chairman and CEO, stated "We made significant investments on AKANTIOR® throughout 15 years of rigorous research and are looking for ways to maximize our asset's potential. As we advance towards a regulatory approval in dozens of European Countries, we are excited to partner with Avanzanite, as this collaboration promises to accelerate access to our drug candidate to patients in several markets that are outside of our current commercial focus." Mr. Chines continued, "Avanzanite's management team brings a substantial track record in delivering orphan medicines to niche European markets, which we expect will result in an accelerated return on investment for SIFI." Avanzanite's Founder and CEO, Adam Plich, stated, "Today's announcement bears all the hallmarks of what we're passionate about: Increasing access to orphan drugs for patients suffering from very rare diseases across Europe and optimizing economic returns for our partners. Plain and simple, through this alliance, Avanzanite is not only contributing to market access to those afflicted by the devastation of AK in European markets previously unapproachable to SIFI but is also unlocking additional revenue potential for the Company." ABOUT Acanthamoeba Keratitis (AK): AK is a rare, severe, 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. 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 and it accounts for 50% of blindness among contact lens users. ABOUT AKANTIOR®: AKANTIOR® (polihexanide) is an investigational anti-amoebic polymer that has been granted Orphan Drug Designation by both the European Medicines Agency ("EMA") and Food and Drug Administration ("FDA") for AK. It acts on both the trophozoites and cysts of the protozoan Acanthamoeba. It is formulated at a unique 0.8mg/ml high dose strength which makes it possible to administer as monotherapy eye drops in single-dose containers. Polihexanide is also being developed by SIFI for the treatment of fungal keratitis for which indication it also has FDA Orphan Drug Designation. ABOUT SIFI: SIFI is a leading international ophthalmic company, headquartered in Italy, focusing on eye care since 1935. SIFI develops, manufactures, and markets innovative therapeutic solutions for patients with ophthalmic conditions. SIFI is fully committed through its R&D to improving the quality of life of patients, exporting treatments to more than 25 countries worldwide with a direct presence in Italy, Spain, France, Romania, Mexico, and Turkey. ABOUT AVANZANITE BIOSCIENCE: Avanzanite is a commercial-stage pharmaceutical company, headquartered in the Netherlands, on a mission to redefine the commercialization of orphan medicines to improve patient access across Europe and beyond. Derived from the word 'Tanzanite' – one of the rarest and most underappreciated gemstones on earth – Avanzanite's economic goal is to offer end-to-end commercialization and distribution partnerships to research-based biopharmaceutical originators to unlock the full value of their orphan medicines in European markets. The Company's humanitarian goal stems from their commitment to enabling access to novel medicines for patients who suffer from orphan diseases regardless of where in Europe they may live. Logo - View original content: SOURCE SIFI S.p.A.