September 21, 2020
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BLOG: Dry eye pipeline remains robust

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Despite stalls in development due to COVID-19, eye care providers can look forward to new treatments for ocular surface disease. As our understanding of the disease and its underlying mechanisms broadens, so does the industry's response.

Nasal spray

Oyster Point Pharma’s lead candidate, OC-01, a nasal spray form of varenicline, has shown positive results in topline data released from its phase 3 ONSET-2 trial. The highly selective nicotinic acetylcholine receptor agonist was associated with statistically significant improvement for both sign and symptom endpoints.

The company’s CEO, Jeffrey Nau, PhD, MMS, has said that the patients enrolled in the trials were reflective of a real-world setting with symptoms across a range of severity. He believes that this bodes well for the nasal spray's success in the real world once it hits the market (Koury).

Of interest is the compound’s novel delivery method via a preservative-free aqueous nasal spray, designed to re-establish tear film homeostasis by activating the trigeminal parasympathetic pathway in the nasal cavity to stimulate natural tear film production. The company has noted that it is considering other potential indications such as contact lens intolerance-associated dry eye and presurgical ocular surface optimization.

Eradicating mites

Josh Johnston, OD, FAAO
Josh Johnston

Speaking of novel, Tarsus Pharmaceuticals has presented positive results from its phase 2a and 2b investigations of TP-03 for the treatment of Demodex blepharitis (Gonzalez-Salinas et al., Horn et al.). In the first single-arm, open-label trial, the agent showed rapid, complete and durable efficacy with no serious adverse effects. The randomized trial, for its part, demonstrated that the agent was well tolerated and effective in reducing collarettes and Demodex density through 90 days.

Demodex mites, the most common ectoparasite in humans, can infest the eyelash follicles, meibomian glands and sebaceous glands and are a major cause of chronic blepharitis. In fact, a meta-analysis of almost 5,000 patients revealed that the mites were implicated in 45% of cases (Zhao et al.). Demodex blepharitis can be diagnosed by the presence of collarettes seen via routine slit-lamp examination. There is currently no FDA approved therapeutic for the eradication of Demodex.

TP-03 treatment was associated with a reduction in collarette grade from baseline that was statistically significant as well as a decrease in mean mite density compared with the vehicle control group in the phase 2b study. Patients rated the drop as comfortable. Keep in mind that we commonly use tea tree oil to eradicate Demodex, an approach that can be quite uncomfortable for patients. If approved, TP-03 it would be the first such treatment that has been shown to eradicate the mites.

Dental model

More approvals mean more options for our patients and maybe even bringing us a step closer to the dental model of ocular surface health that we so often discuss. For example, when it comes to meibomian gland health, it would be beneficial for patients to consider a preventive and maintenance approach to ensure good meibum flow.

LipiFlow (Johnson & Johnson Vision) has been shown to improve gland function, tear breakup time and Standardized Patient Evaluation of Eye Dryness scores compared with warm compresses (Pang et al.). In the meta-analysis, LipiFlow was associated with a significantly greater reduction in Ocular Surface Disease Index scores at 2 to 4 weeks and 2 months compared with warm compress.

Other device-based meibomian gland dysfunction (MGD) treatments include Systane iLux (Alcon) and TearCare (Sight Sciences). The former is a portable device that applies light-based heat to the eyelids in a targeted fashion. The latter is a wearable technology designed to melt and clear meibomian gland obstructions.

Using the dental hygiene approach, we could potentially prevent the progression of MGD and arrest further obstruction and loss of gland function with regular thermal pulsation treatments. In the future, we could see a move toward proactivity when it comes to eye health. Just think, we could truly change the standard of care in dry eye and dramatically improve patients’ quality of life. Of course, this would also pay dividends regarding refractive outcomes for our premium IOL patients.

Ongoing innovation in eye care shows just how much more targeted our tools are becoming when it comes to treating the underlying causes of ocular surface disease. For comprehensive eye health, the more the merrier!

References:

  • Gonzalez-Salinas R, et al. Paper 2984-80042. Presented at: Association for Research in Vision and Ophthalmology meeting; May 6, 2020 (virtual meeting).
  • Hom MH, et al. Poster: Randomized controlled trial to evaluate the safety and efficacy of tp-03 for the treatment of blepharitis due to Demodex infestation (Jupiter Study). Presented at: Optometry's Meeting 2020 (virtual meeting).
  • Koury CB. With positive phase III results, Oyster Point Pharma banks $120 Million from public offering. Available at: https://ois.net/with-positive-phase-iii-results-oyster-point-pharma-banks-120-million-from-public-offering. Accessed July 15, 2020.
  • Oyster Point Pharma announces positive results in ONSET-2 phase 3 trial of oc-01 nasal spray for the treatment of the signs and symptoms of dry eye disease. Press release. Available at: https://investors.oysterpointrx.com/news-releases/news-release-details/oyster-point-pharma-announces-positive-results-onset-2-phase-3. Accessed July 15, 2020.
  • Pang SP, et al. Cornea. 2019;doi:10.1097/ICO.0000000000001907.
  • Zhao YE, et al. Ophthalmic Epidemiol. 2012;doi:10.3109/09286586.2011.642052.
Sources/Disclosures

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Disclosures: Johnston reports he is a consultant to Alcon, Allergan, Bio-Tissue, Johnson & Johnson Vision and Shire.