Two Australian ophthalmologists are repurposing a common cholesterol-lowering drug into a topical ocular therapy for dry eye and blepharitis, which was given to a patient as part of an initial trial who went 90 seconds without blinking.
Dr Kenneth Ooi and Professor Stephanie Watson, from the University of Sydney’s Save Sight Institute, have completed a pilot study of their therapy called Atorvastatin, which they believe has the potential to treat both evaporative and aqueous deficient forms of the disease.
Unlike other therapies on the market, the formulation has multiple mechanisms of action and, if successful, could fill a distinct gap in a global market estimated to be worth up to $7.7 billion within the next five years. However, the research will need to overcome funding hurdles to reach the next phase of development.
The tear film stabiliser has been repurposed from oral statins, which have well known cholesterol-lowering and immunomodulatory properties. Pfizer’s Lipitor is the gold standard statin and continues to generate roughly $2 billion per year in sales, despite its patent expiring eight years ago.
Ooi and Watson’s use of statins as a topical ocular therapy for dry eye and blepharitis is novel. It is non-steroidal with no steroid-like related side effects.
According to Ooi, the Australian market is reflective of much of the western world, with treatment choices largely limited to LFA-1 inhibitor lifitegrast (Xiidra) and variants of cyclosporine (such as Restasis, Cequa and more recently Ikervis). There are also many over-the-counter therapies, some of which are wetting agents that don’t address the underlying mechanisms of dry eye. These have a place for minor dry eye but there remains an unmet need for cost-effective, side effect-free treatments for moderate to severe forms of the disease.
“Atorvastatin is multi-modal in its mechanism of action compared to a number of competitors on the market or in the pipeline which have only one or predominantly one mechanism of action,” Ooi said.
In a recent pilot study of 10 patients with blepharitis and dry eye, which often co-exist, Ooi recorded positive results with reduced corneal fluorescein staining and conjunctival redness, improved tear break-up times (TBUT) and normalised Schirmer’s wetting. There was improved blepharitis, as well as dry eye symptom scores.
“One patient in particular was able to keep her eyes open after treatment (without blinking) for 90 seconds. Her initial TBUT was four seconds and her Schirmer’s wetting, initially at 7mm, stabilised to 15mm after one month of treatment,” he said.
“No local or systemic adverse effects were recorded and patients favourably rated acceptability and ease of use of topical statin therapy.”
Ooi now has his sights set on obtaining further clinical data to optimise the dosing frequency. They are looking to offer the opportunity to the pharmaceutical industry and venture capitalists locally and overseas to fund the work.
He hoped Atorvastatin may one day be used to treat evaporative dry eye, as well as the aqueous deficient form, including post-cataract and refractive surgery dry eye, post-intravitreal injection dry eye and Sjogren’s syndrome, as well as allergic dry eye and ocular pain.
The work stems from Ooi’s research into statins as a potential oral steroid- sparing agent for uveitis at the Institute of Ophthalmology, University College London.
“Knowing that inflammation is associated with dry eye and that research indicates there may be an excess of free cholesterol in the lipid layer in meibomian gland dysfunction contributing to evaporative dry eye, statins came to me as being potentially ideally placed as repurposed novel tear film stabilisers,” he said.
They have secured patents for topical statins as a novel tear film stabiliser in Australia, Japan and Europe, and are filing in the US. There is the potential for novel spin-off patent generation as well.