The dynamics of Demodex blepharitis are analogous in many ways to those of dry eye disease (DED) prior to 2004, due to the large patient population suffering with a disease that impacts daily living and diminishes quality of life with no FDA-approved therapeutics. In the recent Atlas study, 80% of Demodex blepharitis patients report the disease negatively impacts their daily life, and it may have clinical, functional and psychosocial impacts.1,2 As with DED, Demodex blepharitis is quite common, but many patients are either not being identified or are being misdiagnosed—primarily due to symptom overlap and comorbid ocular surface diseases. Currently, there are no U.S. Food and Drug Administration (FDA)-approved therapies for Demodex blepharitis. That is why Tarsus sees a significant opportunity to help these patients with unmet needs.
Addressing Demodex blepharitis at the source
In contrast to DED, a major difference when it comes to Demodex blepharitis is the potential to directly address the root cause. Since DED is multifactorial, treatment options are typically focused on attacking various inflammatory pathways. However, Demodex blepharitis has a more clear pathophysiology, since the Demodex mite is the root cause of disease.
Read this article from Dr. Edward Holland in The Ophthalmologist as he discusses the significant impact of Demodex blepharitis and new research approaches. https://t.co/sK0EnDOd62 #eyecare #demodex #blepharitis pic.twitter.com/KxfDAuIgpt
— Tarsus Pharmaceuticals, Inc. (@TarsusRx) June 10, 2021
Another significant difference (and advantage) in the diagnosis of Demodex blepharitis versus DED is that an objective, pathognomonic relationship exists between collarettes and Demodex blepharitis.3 Collarettes are waxy, cylindrical debris caused by an infestation of Demodex mites that typically sits at the base of the lash, providing doctors with an easy method of identifying patients with this disease. These collarettes can be seen during a routine slit lamp exam when the patient looks down so the clinician can see the base of the upper lid.
Collarettes, or waxy cylindrical debris, can develop at the base of eyelashes and are caused by a Demodex mite infestation. Discover more about how to identify Demodex blepharitis in your patients: https://t.co/ugtm5yNros #demodex #blepharitis #eyecare pic.twitter.com/XADAzATT94
— Tarsus Pharmaceuticals, Inc. (@TarsusRx) July 28, 2021
The Titan Study
There is a growing interest in Demodex blepharitis, evidenced by the fact that 80% of the related literature has been published in the last five years. The historical body of literature estimates there are 20 million blepharitis cases in the U.S., with about half of those attributed to Demodex; this equates to about 9 million patients.4-7 However, the recently completed Titan Study revealed that Demodex blepharitis may actually affect up to 25 million Americans.8
The Titan study included over 1,000 patients and seven different ophthalmology and optometry investigators across the United States. In the study, clinicians were asked to assess the presence of collarettes in consecutive, all-comer patients who were being seen for various needs, including contact lenses, DED, pre-cataracts, etc.
Results indicated that 58% of these patients presented with collarettes. Since the presence of collarettes is a pathognomonic sign of a Demodex infestation, 58% of these patients had Demodex blepharitis.8 This indicates that Demodex blepharitis may be far more prevalent than conventional thinking based on previous epidemiological estimates, which is why these results are so significant and were presented at this year’s ASCRS Annual Meeting in July.
When considering the approximately 45 million unique visits to the eye doctor every year, a 58% incidence equates to a true in-office, real-world estimate of about 25 million patients, or 1 in 12 Americans.8,9 These are patients who are experiencing redness, itching, irritated eyelids, misdirected or lost lashes, and have often been suffering with this disease for more than 4 years.1
How Tarsus is making a difference
The good news: During a slit lamp exam of the eyelid with the patient looking downward, it’s very easy to detect collarettes that may not be visible when the patient is looking straight ahead. That’s why Tarsus has been focused on educating clinicians and thought leaders about including this small, but crucial step in their slit lamp exam as part of a routine assessment, noting the eyelid is a foundational component of ocular health.
Additionally, Tarsus is progressing with their clinical development program for TP-03—their lead investigational drug being evaluated for the treatment of Demodex blepharitis. TP-03 is a topical ophthalmic formulation of lotilaner, a well-characterized anti-parasitic agent that paralyzes and eradicates Demodex mites by selectively inhibiting parasite-specific GABA-CI channels. Lotilaner is highly lipophilic; Tarsus believes this property may help the drug eradicate the mites by penetrating into the oily sebum in the lash follicles where they reside.
TP-03 has now shown positive results in its first pivotal study, the Phase 2b/3 Saturn-1 trial, where it demonstrated complete resolution of the signs of Demodex blepharitis and met all primary and secondary endpoints with no serious treatment-related adverse events or discontinuations due to treatment. These results are very consistent with the Phase 2 clinical trials and are encouraging for the potential of TP-03 to treat patients with Demodex blepharitis. Currently TP-03 is being studied in a second pivotal Phase 3 trial, Saturn-2, which is expected to read out in the first quarter of 2022. If the results of this trial are positive, Tarsus expects the results from Saturn-1 and Saturn-2 to support the submission of a New Drug Application to the FDA for TP-03 to treat Demodex blepharitis.
The Saturn-1 pivotal trial evaluating the treatment of Demodex blepharitis showed positive results and met all pre-specified primary and all secondary endpoints. https://t.co/ioxi35fxrR #demodex #blepharitis #eyecare pic.twitter.com/1dV580D1MG
— Tarsus Pharmaceuticals, Inc. (@TarsusRx) June 21, 2021
From a pipeline perspective, Tarsus is also developing other high unmet need additional applications for lotilaner, including meibomian gland disease (MGD), rosacea, Lyme disease prevention, and community malaria reduction. A Phase 2 study of lotilaner to treat MGD is expected to begin later this year. Since Demodex infestation may cause MGD, this is potentially another treatment on the horizon for a common disease without efficacious therapies currently available that eyecare professionals encounter in their patient populations. Tarsus has also begun a Phase 1 clinical study for TP-05, an oral formulation of lotilaner, being evaluated for the prevention of Lyme disease.
Through their strategic partnership with LianBio Ophthalmology, Tarsus also plans to develop TP-03 in Greater China, where up to 40 million individuals potentially suffer with Demodex blepharitis and up to 70 million with MGD.
We’ve initiated a strategic partnership with LianBio to advance development of our lead candidate for Demodex blepharitis and Meibomian Gland Disease in Greater China, expanding access for patients in need. Read more ➡️ https://t.co/lCORRkuOXw pic.twitter.com/J3FoHlpnrj
— Tarsus Pharmaceuticals, Inc. (@TarsusRx) March 29, 2021
Tarsus owns the global rights to lotilaner for all uses in humans and aims to bring this innovation to market worldwide to revolutionize treatment for patients in need.
Sources
- Yeu E, Holdbrook M, et al; Psychosocial Impact of Demodex Blepharitis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1261.
- Schachter S, Yeu E, et al; Clinical Manifestations of Demodex Blepharitis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1268.
- Gao Y, Di Pascuale MA, Li W, et al. High Prevalence of Demodex in Eyelashes with Cylindrical Dandruff. Investig. Ophthalmol. Vis. Sci. 2005;46(9):3089–3094.
- Data on file. Tarsus Pharmaceuticals, Inc. 2019.
- Howden LM, Meyer JA. Age and Sex Composition: 2010. United States Census Bureau, Department of Commerce, Economics and Statistics Administration. 2011.
- Paulsen AJ, Cruickshanks KJ, Fischer ME, et al. Dry Eye in the Beaver Dam Offspring Study: Prevalence, Risk Factors, and Health-Related Quality of Life. Am J Ophthalmol. 2014;157(4):799–806.
- Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on the Epidemiology of, and Associated Risk Factors for, MGD. Investig. Ophthalmol. Vis. Sci. 2011;52(4):1994–2005.
- Sadri E, Yeu E, et al. The prevalence of collarettes and Demodex blepharitis in ophthalmology and optometry practices. Presented at: ASCRS 2021. Abstract 75009.
- Wilson FA, Stimpson JP, Wang Y. Inconsistencies Exist in National Estimates of EyeCare Services Utilization in the United States. J. Ophthalmol. 2015; 2015:435606. doi: 10.1155/2015/435606. Accessed 01/25/2020.
