New eye drop formulations are making dry eye treatment more affordable and accessible, especially for more severe sufferers. But Australia has often played catch up, as RHIANNON BOWMAN reports.
In one of Insight’s popular Soapbox column’s last year, Dr Brendan Cronin from the Queensland Eye Institute, expressed his views on whether enough was being done for dry eye patients in Australia.
As an example, he pointed out that while first-generation ciclosporin compounds have been available in the rest of the world for more than a decade, the first Therapeutic Goods Administration (TGA)-approved ciclosporin in Australia (Cequa) only became available last year.
Although Ikervis (another ciclosporin) and Xiidra (lifitegrast) have since expanded the suite of products available locally, Cronin pointed out that the cost of obtaining TGA approval for new medications means a small market like Australia is often overlooked by pharmaceutical companies due to the high cost of gaining an approval.
While several therapies are accessible via the Pharmaceutical Benefits Scheme (PBS), he noted Medicare has not yet adopted any procedural treatment for dry eye in the MBS schedule, meaning expenses are borne by patients.
His comments struck a chord; the column attracting thousands of views from Australian eyecare professionals.
This month, Insight invited eyecare professionals with a strong clinical presence in dry eye to weigh-in about the current dry eye treatment options and discuss what is happening to address issues around the cost of treatment.
Supply not keeping up with demand
Clinical optometrist Mr Jason Holland practises at two locations in Brisbane, The Optical Superstore and The Eye Health Centre. At the latter, he operates a co-management clinic with ophthalmologist Dr Andrew Apel to manage and review patients with diabetes, glaucoma and ongoing conditions including dry eye.
Holland says more specific treatment options are emerging.
“For many practitioners, over-the-counter lubricant eye drops have been their go-to treatment for dry eye disease for many years, and for mild cases, the DEWS II report supports this approach is appropriate,” he says.
“Initially we had a plethora of lubricants to support the aqueous layer, however, for many patients it is the lipid layer which is deficient. In recent years there have been a number of new lipid containing products released in Australia, so I feel that we are being supported by industry in regard to innovation.”
While lubricants are good at managing symptoms, Holland says patients with more severe disease are looking for treatments to improve the underlying conditions.
“We have been lucky to have access to many devices to treat dry eye in Australia, however, there is no rebate for these procedures so the cost of therapy can be a limiting factor despite a growing demand from the community,” he says.
Holland believes the TGA is not delaying access to dry eye treatments – but COVID is.
This is particularly the case for Cequa, Australia’s first approved ciclosporin eye drop. The TGA approved the prescription-only immunosuppressant, indicated to increase tear production in patients with moderate-to-severe dry eye, in February 2020.
“Research has shown Cequa is a promising medicine – and it’s preservative-free, and TGA-approved, but since COVID hit, we can’t get stock. Patients are desperate to get more. It’s a challenge because Australia is a small market, globally,” Holland says.
“Many of my patients have had incredible success with Cequa so I was forced to find an alternative when stock from America became limited. Initially I sourced compounded ciclosporin with an aqueous base from a local hospital, however, I am now keen to assess the effectiveness of [new drug] Ikervis as an alternative.”
He says local practitioners also hope to soon have access to Alcon’s iLux MGD treatment device for dry eye, which debuted at SECO International in 2019.
“iLux is a device which practitioners can use in their clinics. It is unique in that it heats the meibomian glands from the inside like the Lipiflow device. The device then simultaneously expresses the meibomian glands,” Holland says.
Other treatments, such as the ciclosporin-containing Restasis (AbbVie/Allergan), have not met with TGA approval but are accessible via the Special Access Scheme (SAS).
Holland says a lot of research is being carried out into potential dry eye treatments, predominantly eye drops, with new and existing players in the ophthalmic industry vying for market share. This is particularly exciting for more severe disease sufferers who may not respond to the multitude of other eye drop therapies available, currently dominated by therapies for aqueous deficiency.
One of those is pharmaceutical company Seqirus, a subsidiary of the Melbourne-based biotechnology company CSL, which is behind two novel treatments.
This includes the aforementioned Ikervis (ciclosporin 0.1% ophthalmic emulsion), which is a treatment for severe keratitis in adult patients with dry eye disease when artificial tears are insufficient.
The other product, Cationorm (cationic nanoemulsion), listed on the Pharmaceutical Benefits Scheme from 1 August, is a hydrating and lubricating emulsion that protects the eye surface and relieves irritation due to persistent dry eyes.
“Seqirus is a new company to enter the dry eye market that virtually no one has heard of before. Their mineral oil emulsion for evaporative dry eye – Cationorm – has TGA approval, and while I’ve got product samples, I want more,” Holland says.
“Ikervis is certainly going to be utilised in my practice. Having a preservative-free alternative will be wonderful for many of my patients and the once-a-day dosing is a bonus. Like most ciclosporin products, patients will need to wait 90 days to assess its effectiveness.”
Holland says there are also other major companies, which traditionally target treatments for the posterior of the eye, getting further into dry eye treatments, and directly marketing to optometrists.
One of those is Novartis, which acquired dry eye drug Xiidra (lifitegrast ophthalmic solution) in a $7.5 billion deal in 2019. It was included on the Australian Register of Therapeutics Goods (ARTG) the same year. It is a prescription treatment indicated for moderate to severe dry eye in adults for whom prior use of artificial tears has not been sufficient.
“Xiidra is designed to manage inflammation. Although the government is not restricting access to this unique product, there is a challenge in prescribing it as optometrists need to get SAS approval for every script, as per TGA rules,” Holland says.
For more severe dry eye sufferers, Holland says it’s encouraging to see the rollout of novel eye drop therapies in Australia because they allow any registered optometrist with therapeutic endorsement access to treatment, without needing to outlay thousands of dollars in specialist treatment devices.
“Eye drops like Cequa, Xiidra and now Cationorm take away the cost barrier to treatment for patients. Eye drops are not cost prohibitive, compared to other treatments, like LipiFlow or intense pulsed light (IPL) that some patients simply can’t afford.”
Despite the prohibitive cost of some treatment options, Holland suspects that seeking a new Medicare item number for treating dry eye could be a bridge too far.
“In 2015, when an MBS item number for removal of foreign body was introduced, it was a different environment politically. We need critical mass in order for a dry eye therapy to be MBS-listed, but at the moment, there might only be about 20% of optometrists who are actively treating dry eye,” Holland says.
“We might have more luck with private health funds to contribute towards the cost of procedural aspects of dry eye treatment.”
Fees and profit margin
Ophthalmologist Dr Kenneth Ooi, from the University of Sydney’s Save Sight Institute, says Australia has experienced a slow uptake in accessing the world’s leading dry eye therapies – and there are many reasons for this.
Ooi himself is hoping to address a major unmet need by repurposing a common cholesterol-lowering drug into a topical ocular therapy for dry eye and blepharitis, called Atorvastatin. Along with Professor Stephanie Watson, they have shown promising results in a pilot study and believe their therapy has the potential to treat both evaporative and aqueous deficient forms of the disease.
Generally, Ooi says one of the main barriers to Australia accessing the most innovative therapies include licensing policies of global pharmaceutical companies, which can impact, or delay therapies being brought into Australia a lot of the time.
“We’re dependent somewhat on pharmaceutical companies who want to take up a license to distribute in Australia. Where do they see something that differentiates the potential new dry eye product? It’s a crowded market, so a new product has to have a hook,” Ooi says.
“An innovative, novel product would therefore have an increased price point and likely need a reimbursement capability. It needs to be shown to be cost- effective compared to currently reimbursed therapies, so eligibility criteria, as designated by Pharmaceutical Benefits Advisory Committee (PBAC), may limit uptake of the drug to smaller patient groups via the PBS. For example, limiting reimbursed treatment to patients with an Ocular Surface Disease Index (OSDI) score greater than 30.”
Ooi says in Australia there are a limited number of companies willing to bring in a new drug.
“From an innovating company perspective, they need to recoup investment and failed products investment. It can be to the order of a 20% reinvestment strategy into new research, and $2 billion, on average, to bring a new drug to the global market,” he says.
In a smaller market like Australia, which has two-thirds the population of California, Ooi says products may also need higher pricing once dollar exchange rates are factored in.
From a PBAC perspective, any new product brought to market must have already been reviewed and approved for Australia by the TGA and has to be cost-effective, he says.
“It’s a balance. The patient population with the eye health condition has to be large enough for the licenser, but to achieve the desired price point, the PBAC may mandate additional criteria to limit its use so that it remains cost-effective.”
Ooi says the PBAC has a remit to allow reimbursed access to alternative, cost-effective treatments. PBAC cost-effectiveness (health economics) determines the amount of reimbursement.
“For example, if a treatment is approved for PBS reimbursement, a pensioner pays $6 for the product, and the government makes up the shortfall of $34, for a product that costs $40 from the licensor. If a product is not reimbursed via the PBS, then it may only be available for ‘private sale’, so the patient must pay the full price, including dispensing fees, which may be prohibitive,” he says.
“When reimbursing therapies via the PBS, the government is deciding how to divide money from a pool of a set size with other medications in place which already are reimbursed and work.”
Regulatory fees can also affect profit margin and are a consideration when deciding whether to bring a product to Australia.
“The parent pharmaceutical company sets in-licensing fees and negotiates fees for the licensing company purchasing the product. Then there are registration fees with the TGA and PBAC, and ongoing fees maintaining registration,” Ooi says.
He says the TGA assesses products for efficacy, safety, and whether manufacturing processes and facilities are appropriate, which results in fees being incurred.
“For a European approved drug, European Medicines Agency (EMA) registration paperwork and pharmacovigilance assessment is similar to Australia. For a US approved drug, FDA re-writing costs needs to be incurred. Additional safety data may be requested from regulatory authorities which add to ongoing costs.”
Ooi says Australian eyecare practitioners’ uptake of innovative treatments is generally slow, compared to their global counterparts, given that dry eye drug development is not usually done in Australia.
“And we tend to be conservative preferring to be presented with randomised controlled trial/real-world data and using well- established products,” he says.
But once a new therapy is introduced, Ooi says the profession has enough respected advocates in ophthalmology and optometry.
“Australia has a combination of well-trained ophthalmic and optometric eyecare providers; education on therapeutic prescribing rights takes place now at an undergraduate level in optometry; there is a lot of interest in dry eye in optometry, and where access to ophthalmology in country areas is difficult, optometrists fill this need.”
Ooi says it may be feasible to use compounding chemists to get around a lack of access to some leading products but only if the products are TGA-approved and included on the ARTG but not commercially available in Australia, or unavailable via the SAS.
“For example, preservative-free formulations that are out of stock in Australia can be compounded. A drug can also be prescribed off-license/ label, but it has to be formulated and made by a compounding pharmacy that approves of its use,” he explains.
“Individual Schedule 5 TGA exemptions allow for specific individual patient drug needs but products cannot be commercialised or produced in large-scale quantities.”
Tip of the iceberg
The cost of treatment is an aspect of dry eye that optometrist and co-owner of Alleve Eye Clinic in Adelaide, Dr Jennifer Rayner, knows well.
With a background in both independent and corporate optometry, she initially owned and operated a regular optometry and concurrent dry eye practice for two years, then broke away to open a clinic where she could devote her time and resources to only dry eye patients.
As a result, she established South Australia’s only dedicated dry eye clinic.
“I don’t refract, or fit contact lenses – I purely diagnose and treat dry eye,” Rayner says. “Dry eye is a growing clinical field, still being recognised and, at times, dismissed. It’s a huge problem, more than people realise.”
Alleve Eye Clinic opened in 2016 and has taken a few years to get off the ground, Rayner says.
Her patient referrals come from a wide variety of sources, including GPs, optometrists, ophthalmologists, rheumatologists, dermatologists, pharmacists – and Google “because patients don’t need an official referral to see me – people are looking for a solution”.
“Dry eye takes time. It can be notoriously hard to treat. Diagnosis is relatively straight forward but managing patients and testing treatment options takes time. Some patients have been suffering for 15 to 20 years. There is no one solution that works for everyone. Fortunately, the Tear Film and Ocular Surface Society (TFOS) have established treatment protocols (DEWS I and II) but it still involves trial and error for each patient,” she says.
Despite the inherent difficulty in finding successful solutions, Rayner says treatment options have come a long way in the last five years, with products like Optimel Manuka eye drops and gel, which feature highly in her practice’s arsenal.
However, she laments that even though dry eye is a growing area, practitioners don’t have an official body where they can exchange information and insight about dry eye treatments, new products, or equipment, she says.
“It’s growing and becoming more accepted, but it seems there is a two- tiered model of dry eye practice evolving. There are those offering dry eye treatment at an entry level, like myopia, and there are those who are taking the next step, like myself, with a dedicated clinic backed by an elevated knowledge of this disease.”
Rayner’s practice model assesses each patient’s dry eye disease – and financial position to afford treatment – on a case-by-case basis.
“We clinically assess patients as part of an initial consultation under Medicare guidelines if they are eligible. We don’t bulk bill. In my experience, patients are so desperate to resolve their dry eye that they will pay out-of-pocket, but they often say, ‘I wish my health fund would cover this’. I initially spoke to one major health fund about covering dry eye, but it was not considered big enough to cover,” Rayner says.
“Some people can’t afford the gap. We take an individual approach to cost and payment. It would be fabulous to see a Medicare rebate for basic imaging like meibography (infrared imaging of meibomian glands). Medicare should be covering meibography, much like Medicare covers a bone x-ray. But it’s not covered.”
Emphasis on education
Optometry Australia (OA)’s chief clinical officer Mr Luke Arundel says the organisation recognises that the incidence of dry eye is high with most people experiencing this condition at some time.
“The rise in dry eye is creating a need within the population for more specialised treatment, hence we are seeing the establishment of dry eye clinics throughout Australia to assist patients manage this condition. We are highly supportive of the establishment of practices dedicated to specific eye conditions and diseases,” he says.
Given the prevalence of dry eye, OA is continuing to provide education and professional development resources for its members.
In July, the US inventor of the IPL procedure, Dr Rolando Toyos, facilitated a dry eye webcast, outlining the basic concept and mechanism of IPL therapy and how it can be incorporated into dry eye treatment, and reviewing existing and new therapeutic dry eye management options available to practitioners.
Simultaneously, Arundel says OA is continually lobbying for the expansion of the MBS schedule. The organisation has a member-based Medicare Services Advisory Group to assist in this area and its policy team is in regular communication with the numerous divisions within Medicare.
But as Arundel points out, lobbying for items to be added to the MBS can be an expensive enterprise.
“Addition of procedural items to the MBS involves a large amount of effort and resources, with the first of these (item 10944: foreign body removal) successfully added to the list after eight years of lobbying from Optometry Australia.”
Arundel confirmed the organisation is not actively advocating for a procedural item for dry eye to be added to the MBS.
“Currently no modifications or additions to our MBS list are being considered until the results of the MBS review for our tranche are handed down. After numerous delays (exacerbated by COVID-19) this is now anticipated to be as late as 2022.”