Drop shows effectiveness for Demodex blepharitis in phase 2a study

October 6, 2020

Special to Ophthalmology Times®

In a phase 2a study, the novel topical drop TP-03 (Tarsus Pharmaceuticals) was found to be safe and effective for treating Demodex infestation, a frequent cause of blepharitis.1

The drop began working in 2 weeks and lasted through the 90-day study period.

Blepharitis affects at least 20 million individuals in the United States and is frequently the reason patients visit an eye care provider.2-5 As the most common type of ectoparasite found in humans, Demodex mites are highly prevalent in low numbers.

Related: Diving into dry eye can help physicians solve patients' woes

An infestation of Demodex folliculorum, however, causes 45% of blepharitis cases—an estimated 9 million Americans.8-11 Currently, there is no FDA-approved treatment for Demodex blepharitis.

The single-arm, open-label Mars study included 15 patients who received 1 drop of TP-03 in each eye twice a day for 28 days. The prespecified efficacy end points were a decrease from baseline in mean collarette score and mite density at 28 days.

The decrease in both mean collarette score and mite density demonstrated statistical significance—P value of less than or equal to .013 and less than .001, respectively—as early as 14 days after treatment initiation. TP-03, which targets the mites’ nervous system, causing paralysis, was well tolerated, with no treatment-related adverse events (AEs) reported.


Demodex infestation

Collarettes, sometimes called cylindrical dandruff, are a pathognomonic sign of Demodex infestation and are easily seen with a routine slit-lamp examination.

When mites scratch and feed on the skin, collarettes form as the partially digested epithelial cells, keratin, mite waste, and eggs combine.12,13

Collarettes are typically found at the base of the lash but can migrate up the shaft as hair grows.12 Other signs of Demodex infestation include eyelash disorders, crusting and redness of the lid margin, blepharoconjunctivitis, and blepharokeratitis.

Related: New techniques probed for managing dry eye disease

Patients with anterior blepharitis present with red, irritated, or itchy eyelids and eyelash debris.

If not properly managed, the condition can lead to tear film instability that causes fluctuating and blurred vision, lid and lash abnormalities, and inflammation of the conjunctiva and surrounding skin.

Surgical patients with inadequately controlled Demodex blepharitis are at risk of suboptimal surgical outcomes. Erythema is often noticeable. Patients may experience contact lens intolerance and reduced wear time and, overall, a reduced quality of life.2,3,11-13

Mars study
The Mars study included patients who had at least 10 collarettes on the upper lid, mild to severe lid margin erythema, and at least 1.5 mites per lash on the upper and lower eyelids combined.

During the study period, patients were directed to discontinue use of any other treatment for blepharitis, including lid hygiene, to isolate the effect of TP-03.

Patients administered 1 drop in each eye twice a day for 28 days and were followed for 90 days. Efficacy was measured by a decrease in collarettes and in mite density.

Safety was assessed via treatment-related AEs and an evaluation of any changes in visual acuity, IOP, and slit-lamp biomicroscopy.

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A statistically significant reduction in collarettes and mite density began at day 14 and was maintained through 90 days. No treatment-related AEs were observed, and there were no clinically significant changes in visual acuity, IOP, or slit-lamp biomicroscopy findings.

At 97% of visits, patients rated the drop as “neutral” to “very comfortable.”

Jupiter
Following the Mars study, TP-03 results from the Jupiter study, a randomized controlled trial that included 60 participants, were recently presented by Milton Hom, OD.14

The findings further demonstrated that TP-03 was well tolerated and effective in reducing collarettes and Demodex density through 90 days in patients with Demodex blepharitis.

Hom reported that the change in collarette grade demonstrated statistically significant decreases for both eyes, upper and lower eyelid margins, compared with the vehicle arm as early as day 14.

TP-03 showed statistically significant decreases in mite density at day 28, and its effect on both measures persisted for an additional 2 months following treatment.

There were no treatment-related AEs, and patients reported that the drop was comfortable.

Related: Understanding the expanding role of IPL in dry eye disease

Conclusion
An effective and comfortable treatment for Demodex blepharitis remains a large unmet need because there is currently no FDA-approved treatment.

TP-03 has been studied in 4 phase 2 investigations that include a total of nearly 100 patients on active drug. Data show rapid, complete, and durable efficacy, with no treatment-related AEs.

Notably, patients report that the drop is comfortable, and none have discontinued use due to tolerability. Tarsus is developing TP-03 in a multidose, preserved formulation and expects to begin a phase 3 trial this year.


About the author

Roberto Gonzalez-Salinas, MD
e:dr.gonzalezsalinas@apec.com.mx.
Gonzalez-Salinas is an associate researcher at the Asociación para Evitar la Ceguera en México in Mexico City. He is a consultant for Allegro Ophthalmics, Kedalion Therapeutics Inc, Laboratorios Sanfer, and LayerBio Inc.

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REFERENCES

1. Gonzalez-Salinas R, Ramos-Betancourt N, Corredor-Ortega C, et al. Pilot study to evaluate the safety and efficacy of TP-03 for the treatment of blepharitis due to Demodex infestation (Mars study). Paper presented at: Association for Research in Vision and Ophthalmology 2020 Virtual Meeting; June 26, 2020

2. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Panel Guidelines: Blepharitis. San Francisco, CA: American Academy of Ophthalmology; 2013. Accessed TK. www.aao.org/ppp

3. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and disease. Ocul Surf. 2009;7(suppl s):S1-S14. doi:10.1016/s1542-0124(12)70620-1.

4. Harmon M. Market Scope Dry Eye Analyst Report, 2014

5. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Opthalmol Vis Sci. 2011;52(4):1922-1929. doi:10.1167/iovs.10-6997a

6. English FP. Demodex folliculorum and oedema of the eyelash. Br J Ophthalmol. 1971;55(11):742-746. doi:10.1136/bjo.55.11.742

7. Rufli T, Mumcuoglu Y. The hair follicle mites Demodex folliculorum and Demodex brevis: biology and medical importance. a review. Dermatologica. 1981;162(1):1-11. doi:10.1159/000250228

8. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Panel Guidelines: Blepharitis. San Francisco, California: American Academy of Ophthalmology; 2013. www.aao.org/ppp.

9. Coston TO. Demodex folliculorum blepharitis. Trans Am Ophthalmol Soc. 1967;65:361-392

10. Gao YY, Di Pascuale MA, Li W, et al. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Opthalmol Vis Sci. 2005;46(9):3089. doi:10.1167/iovs.05-0275

11. Zhao YE, Wu LP, Hu L, Xu JR. Association of blepharitis with Demodex: a meta-analysis. Ophthalmic Epidemiol. 2012;1(2):95-102. doi:10.3109/09286586.2011.642052

12. Fromstein SR, Harthan JS, Patel J, Opitz DL. Demodex blepharitis: clinical perspectives. Clin Optom (Auckl). 2018;10:57-63. doi:10.2147/OPTO.S142708

13. Nicholls SG, Oakley CL, Tan A, Vote BJ. Demodex species in human ocular disease: new clinicopathological aspects. Int Ophthalmol. 2017;37(1):303–312. doi:10.1007/s10792-016-0249-9

14. Hom MH, Ceballos JC, Massaro-Corredor M, et al. Randomized controlled trial to evaluate the safety and efficacy of TP-03 for the treatment of blepharitis due to Demodex infestation (Jupiter study). Poster presented at: Optometry’s Meeting 2020