CRANBURY, N.J. - July 13, 2023 - PRLog -- IVIEW Therapeutics Inc. a clinical stage biotechnology company focusing on developing innovative ophthalmic therapeutics, organized a panel of dry eye experts and clinicians to gain key insights on dry eye treatment innovations. The panel included:

Francis Mah, MD, Director of Cornea and External Disease and Co-Director, Refractive Surgery at Scripps Clinic Medical Group in CA.

George Magarth, MD, Board-certified ophthalmologist and CEO of Lexitas, an ophthalmology focused clinical CRO.

Achim Krauss, PhD, former President and CEO of AxeroVision taking two drugs from the preclinical stage to IND and clinical proof-of-concept for treatment of dry eye disease, concluding in a successful exit in 2022.

Houman Hemmati, MD, PhD Board-Certified ophthalmologist, and Chief Medical Officer of two companies developing treatments for refractive errors and acquired blepharoptosis.

Dry Eye Disease (DED) has been considered a multifactorial, progressive disorder of the ocular surface resulting from tear film abnormalities accompanied by ocular surface inflammation. While the prevalence of DED is difficult to report due to varying definitions and diagnostic criteria, the disease affects an estimated > 5% of the global population (i.e., about 385 million people), with some regions of the world reflecting > 30% of the population (1). In the United States, it is estimated that as many as 3.2 million women and 1.7 million men over the age of 50 have DED with a projected 40% increase in number of patients affected by 2030 (2, 3). Even so, the age of DED onset is decreasing, as incidence increases with the widespread and growing use of cell phones, handheld computers and reading devices. Side effects of topical glaucoma medications preserved with benzalkonium chloride can also aggravate DED symptoms.  This too represents a substantial problem, as the number of glaucoma patients soon will approach 80 million worldwide as the population ages (4). Growth Plus Reports estimates the dry eye market is expected to grow at a CAGR of 5% from 2021 to reach US$ 8.92 Billion by 2030, owing to technological advancements and the development of novel diagnostic tools and the increasing burden of dry eye disease.

Four questions were presented to each of the panelists and their responses are as follows.

On June 30, 2023, Bausch+Lomb (B+L) announced the acquisition of Xiidra and other ophthalmology assets from Novartis for $1.75B.  What's your reaction to this announcement and its potential impact on the ocular market, particularly dry eye disease?

Dr. Mah: B&L has a  newly FDA approved product, perfluorohexyloctane, ready to be launched in late 3Q or early 4Q 2023, which will be marketed as a first line non-anti-inflammatory, so this acquisition makes sense to offer a complete portfolio for dry eye - they earlier acquired an OTC artificial tear from J&J, Blink.  So going from Blink, to Meibo, to Xiidra or using the combination, they have arguably the most complete dry eye portfolio.

Dr. Magrath: B&L is creating a powerful portfolio of anterior segment assets.  In addition to Meibo and Xiidra, they added Blink tears last week as well.  They appear to be covering the various mechanisms of DED, Meibo for the more evaporative/MGD patients and Xiidra for the more inflammatory and aqueous deficient patients.  This underpins dry eye as a multifactoral disease requiring different treatments for different patients.

Dr. Krauss: B&L is being more acquisitive again since Brent Saunders took over. Clearly, B&L wants to remain a key player in ophthalmology. In contrast, Novartis has been decreasing its footprint and interest in ophthalmology, first with divestiture of Alcon a few years ago and now of some key front-of-the-eye products. As it pertains to being a potential strategic pharma partner, B&L clearly remains in the game, whereas Novartis probably not anymore for front-of-the-eye products. On the other hand, Alcon has stepped in again trying to generate an Rx portfolio. Viatris is another, fairly new potential strategic partner in ophthalmology.

Dr. Hemmati: B+L's acquisition of Xiidra shortly after it secured FDA approval of Miebo, proves that the market for branded prescription DED treatment is alive and well. Moreover, it shows us that DED isn't just one disease, but rather one characterized by one or more concurrent etiologies, each of which must be separately addressed to achieve acceptable clinical outcomes -- inflammation, evaporation, and symptoms.

There's a pipeline of innovative products for dry eye treatment such as the recent approvals of Miebo™ (perfluorohexyloctane) and VEVYE™ (cyclosporine ophthalmic solution) 0.1% from Novaliq, and NDA filing of Aldeyra's reproxalap.  How do you view the future of dry eye disease and the development of new treatment options?  What do you believe are the remaining unmet needs in dry eye disease management?

Dr. Mah: The main challenge is access/formulary coverage.  Even with what we have available, access is a huge hurdle and until access improves, there will be challenges for clinicians, patients, and new drugs. The main reason dry eye patients complain is due to symptoms, and they are looking for relief from these symptoms.  Whether the eyes look better or have reduced signs of dry eye, if the symptoms are not improved, patients are disappointed, which leads to clinicians who prescribed the meds to be disappointed in the results and reduces the enthusiasm for that med.  I think in order for a dry eye drug to be successful, it has to act quickly - within 1-2 weeks - it has to improve symptoms significantly, for the majority of patients who try it - 80-90% at least.  If this occurs, patients will want to use it, they will provide positive feedback to clinicians, and clinicians will fight for access for their patients.

Dr. Magrath: The ophthalmic market will continue to move towards novel and differentiated mechanisms of action.  The anti-inflammatories now have multiple products, including generic cyclosporine, and appear to be well covered.  There is plenty of room in the market to attack different mechanisms, as DED is multifactorial and only a portion respond to the current marketed products.  DED will continue to become more segmented as diagnostics improve the identification of the underlying pathobiology and more alternative treatments become available addressing different aspects of the disease.

Dr. Krauss:. New treatments for DED in general could still benefit from anti-inflammatories with better efficacy and tolerability compared to Xiidra and CsA products. That includes aqueous deficient DE. Unless the second and major cause of DE, MGD, has good treatment options available just addressing lacrimal insufficiency does not majorly improve tear abnormality and DE. Consequently, targeting MGD will become more of a focus for new DED therapeutics I believe. Once more mechanistically differentiated products for the treatment of DED are available, the field will probably follow the glaucoma field where most patients are on multiple mechanistically different meds.

In short, I believe there is still room for more efficacious and better tolerated drugs for DE treatment until the equivalent of the PGs for glaucoma therapy is discovered. I do not see that in the currently marketed drugs or those in clinical development.

Dr. Hemmati: We are seeing numerous options, which is ultimately far better for patients than having just one or two drugs available for DED. Specifically, these options allow eyecare professionals to customize treatments for each patient, allowing them to try different options and land on the one(s) that best address each patient's unique presentation and complaints. The greatest unmet needs at this point are broader-spectrum non-steroidal drugs that block inflammatory cells and pathways specific to DED, as well as treatments that cause rapid symptomatic relief across a broad spectrum of DED patients.

Anti-inflammatory therapies are often associated with poor compliance secondary to delayed onset or poor tolerability. Neurosensory abnormalities now recognized as contributing to the underlying disease, therefore offer new targets for treatment. For example the targeting of TRPM8, a cold-sensing receptor located on the cornea and eyelid that has the potential to relieve dry eye signs and symptoms is currently in development.  How do you believe this new mechanism can be beneficial to patients suffering from DED and how would it fit into the existing treatment paradigm for DED?

Dr. Mah:  I think they could be successful if you can find a sign that would be statistically successful in an FDA registration trial, and if the symptom relief is overwhelming - 80-90% of patients feel significant relief which translates to clinical significance.

Dr. Magarth: This is a differentiated mechanism that is quite unique in the DED world.  It has the advantage of an immediate soothing effect in a way that should differentiate from current therapies.  I personally would prescribe it because of the almost immediate effect it has, which is not the case with most current products.

Dr. Krauss: TRPM8 represents a new mechanism and approach. As such it stimulates lacrimal function, i.e., Schirmer test and hopefully corneal staining (with a delay). My biggest questions are about tolerability of the product (cool vs cold sensation; comfortable?), onset of action, and whether there is any impact on MGD parameters (given the majority of DED is evaporative in nature). Application as an eyelid wipe includes a component of mechanical MGD treatment (lid massage); but that is the same for the vehicle group. Differentiation of an MGD related parameter will only be achievable if there is a direct (or indirect) impact on the gland and quality and quantity of meibum production and delivery to the ocular surface (via open gland orifices in the lid margin). Even in the absence of an MGD effect, a TRPM8 targeting drug would still find widespread acceptance if it beats other drugs on efficacy and tolerability.

Dr. Hemmati: Whereas other DED therapies target one underlying etiology of DED, none are currently able to address the ocular discomfort that is common across all dry eye patients. It is exciting to have other treatments in development with a new mechanism that could potentially address the full spectrum of dry eye patients, regardless of underlying etiology.

A novel TRPM8 receptor agonist (IVW-1001) is under development by IVIEW Therapeutics with a Phase I/II clinical trial to begin enrollment by Q1 2024.  It is developed as an eyelid wipe which has been shown as an effective route of administration for DED. What's your reaction to this unique route of administration and its relevance/benefits to DED patients?

Dr. Mah: I like the eyelid wipe idea since clinicians are used to discussing wipes with patients with MGD or blepharitis.  I also like the potential for this to be used in CTL wearers who wouldn't have to remove CTLs to apply. However, patients with artificial lash extensions, or eyelid make up, may not be enthusiastic.

Dr. Margrath:  I like the application of the eyelid wipe.  Older patients and less dexterous patients sometimes have difficulty with eye drops and the eyelid wipe is a good alternative delivery method.  The targeting of TRPM8 provides almost fast relief, which may lead to high patient satisfaction.  IVW-1001 is differentiated from the current market and the current development pipeline.

Dr. Krauss: It is a differentiator compared to eye drops. That is important since DED is an age-related disease and elderly patients often struggle with eye drop administration. An eyelid wipe seems to represent an easier way of applying a drug and cause less struggle among the elderly (and even younger patients who struggle with eye drop administration). That of course assumes penetration of the drug into the eyelid proper through the dermal surface, from where it finally achieves the ocular surface tissues (cornea) where the channels are located. Another advantage is that potentially a majority of the drug applied will actually and eventually reach the ocular surface tissues as it traverses the eyelid, in contrast to an eye drop which delivers only a very small percentage of its "payload" to the tissues while the vast majority of an eye drop drains away via nasolacrimal duct within about one minute. Eyelid application is likely to provide a longer duration of action compared to an eye drop, requiring less frequent dosing (QD or BID?) which would be a convenience advantage. At a minimum, IVW-1001 should have a tolerability advantage over existing drugs as a result of its differentiated route of administration. Most likely it will also have a dosing frequency advantage. Both would be major patient benefits.

Dr. Hemmati: Many patients with dry eye simply do not like putting in eyedrops, whether it is because doing so is cumbersome, difficult, or that eyedrops are incompatible with contact lenses. Additionally, eyedrops can roll down the face or cheek or into the nose, causing discomfort. Therefore, a newer, less invasive route of administration can provide a lot of benefits to patients with DED. This is an exciting potential advance for the treatment of DED.

The expert opinions provided by Dr. Mah, Dr. Magrath, Dr. Krauss, and Dr. Hemmati shed light on various aspects of the dry eye treatment landscape and the potential impact of recent developments. Overall, the experts expressed their optimism for the development of new treatments for dry eye disease, particularly those that address unmet needs, provide symptomatic relief, and have better efficacy and tolerability. They emphasized the importance of a comprehensive approach to dry eye treatment, considering its multifactorial nature and the diverse underlying etiologies that contribute to the condition.

To learn more about IView and it's developments, visit https://www.iviewtherapeutics.com/

References:

1. Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clinical ophthalmology (Auckland, NZ). 2009;3:405. DOI: 10.2147/opth.s5555

2. Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians' Health Studies. Archives of ophthalmology. 2009 Jun 8;127(6):763-8. DOI: 10.1001/archophthalmol.2009.103

3. Schaumberg DA, Uchino M, Christen WG, Semba RD, Buring JE, Li JZ. Patient reported differences in dry eye disease between men and women: impact, management, and patient satisfaction. PloS one. 2013 Sep 30;8(9):e76121. DOI: 10.1371/journal.pone.0076121

4. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. British journal of ophthalmology. Mar 1, 2006;90(3):262-7. DOI: 10.1136/bjo.2005.081224