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Optometric Management

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LEADING OFF: New Innovations Are Coming in the DED Pipeline

Treatments undergoing study may offer future therapies

By: GEORGE W. OUSLER III
Optometric Management August 1, 2022 Vol 57, Issue August 2022 Page(s): 16, 18

While the current therapies for dry eye disease (DED) provide both symptomatic relief and have quelled clinical signs, an array of new treatments are in the pipeline set to join them. These yet-to-be-released treatments can offer advantages, such as the targeted treatment of underlying etiologies. Listed below are some of these upcoming treatments.

AR-15512 (AERIE PHARMACEUTICALS)

  • What it is: Aerie Pharmaceuticals developed a therapeutic target for DED with its AR-15512 (formerly known as AVX-012). It is a small-molecule selective agonist of transient receptor potential melastatin 8 (TRPM8) cold thermoreceptors. AR-15512 is thought to work by permitting continuous activity from TRPM8 channels located on the eyelid and cornea, increasing blink rate and basal tear secretion.1
  • Latest research: COMET-1, a Phase 2b clinical study for AR-15512, shows this therapy is safe, well-tolerated, and effective, with statistically significant improvements across multiple signs and symptoms, including discomfort and dryness, tear production, conjunctival redness, and ocular surface staining.2

In late May, Aerie Pharmaceuticals announced the first patient had been dosed in the COMET-2 study, the first of three planned Phase 3 trials for the registrational program of AR-15512. COMET-2 will evaluate the safety and efficacy of AR-15512, with topline results expected in the second half of 2023. The other two Phase 3 trials are expected to be initiated in the second half of 2022.3

CYCLASOL (NOVALIQ)

  • What it is: Novaliq’s CyclASol (cyclosporine) is a preservative-free topical anti-inflammatory and immunomodulating ophthalmic solution for the treatment of DED. CyclASol contains 0.1% cyclosporine in Novaliq’s water-free EyeSol vehicle, which allows for increased interaction time with the ocular surface, thereby enhancing bioavailability.4
  • Latest research: Both early onset of action and clinically significant efficacy for signs and symptoms of DED were noted in the Phase 2/3 ESSENCE-1 trial, including significant improvements in total and central corneal staining in comparison with the vehicle administered.4,5 Consistent results were noted with the ESSENCE-2 trial, thereby prompting Novaliq to plan on submitting a New Drug Application with the FDA and other regulatory agencies in the near future.5

K-161 (KOWA)

  • What it is: An ophthalmic solution designed to treat moderate to severe dry eye disease.
  • Latest research: A Phase 3 trial began recruiting in June to assess the safety and efficacy of K-161.6 This followed the completion of a Phase 2 study in 2021, which tested safety, efficacy, optimum dosage, and dosing regimen of K-161 in adults who had moderate to severe DED.7

REPROXALAP (ALDEYRA)

  • What it is: Aldeyra’s reproxalap is a reactive aldehyde species (RASP) modulator used to alleviate inflammation in DED and allergic conjunctivitis. Reactive aldehyde species are elevated in both ocular and systemic inflammatory disease.8
  • Latest research: A statistically significant improvement in a pre-specified primary endpoint ­— ocular dryness — was observed in two 12-week, well-controlled trials. Additionally, significant improvements in both ocular redness, through the Phase 2 dry eye chamber trial, and Schirmer’s test, assessed in the Phase 3 TRANQUILITY trial, were seen.9

In June, Aldeyra released results from its Phase 3 TRANQUILITY-2 trial, in which reproxalap achieved its primary endpoints of Schirmer’s test (p=0.0001) and ≥10 mm Schirmer’s test responder proportions (p<0.0001). Based on these results, Aldeyra plans to discuss a New Drug Application with the FDA later this year.10

SI-614 (SEIKAGAKU)

  • What it is: An ophthalmic solution for the treatment of dry eye; it is made from an amphiphilic polymer produced by introducing a hydrophobic group into hyaluronic acid. It is expected to restore the tear film and corneal structure to its normal state, and improve symptoms associated with DED.11
  • Latest research: Seikagaku initiated a Phase 3 clinical trial in May in the United States; clinically beneficial effects were previously confirmed in a Phase 2/3 clinical study.11

VISOMITIN (MITOTECH)

  • What it is: Mitotech’s Visomitin is a small molecule cardiolipin peroxidation inhibitor that works by scavenging reactive oxygen species to target inflammation, corneal and conjunctival damage, tear deficiency, and gland tissue regeneration.12,13
  • Latest research: VISTA 1/2, two completed late-stage DED trials, exhibited significant clearance of staining in a large DED subset with placebo-like tolerability.8 Phase 3 studies for Visomitin for DED are ongoing, with Phase 2 trials ready to commence for other ophthalmic diseases.14

NEW APPROACHES

In this new world of customizable medicine, physicians are leaning on polytherapy approaches to manage ocular surface disease holistically and effectively to treat their DED patients.

All the above therapies, will be welcome additions to manage this complex, multi-faceted, and chronic disease. The future is looking very bright regarding opportunities in treating DED. OM

Mr. Ousler is the senior vice president of Anterior Segment at Ora, Inc. and oversees all DED-related clinical programs. He has 20+ years of experience pioneering pharmaceutical development in DED.

REFERENCES

  1. About AR-15512 Eye Drop. Aerie Pharmaceuticals. Accessed June 10, 2022. https://aeriepharma.com/rd/ocular-surface-disease/ar-15512/
  2. Aerie’s dry eye therapeutic improves symptoms and signs in Phase IIb trial. Clinical Trials Arena. Sept. 16, 2021. https://www.clinicaltrialsarena.com/news/aerie-dry-eye-phase-iib-data/ . Accessed June 10, 2022.
  3. Aerie Pharmaceuticals Announces First Participant Dosed in the Phase 3 Registrational COMET-2 Study of AR-15512 for the Treatment of Dry Eye Disease. Aerie Pharmaceuticals. May 24, 2022. https://investors.aeriepharma.com/news-releases/news-release-details/aerie-pharmaceuticals-announces-first-participant-dosed-phase-3 . Accessed June 10, 2022.
  4. CyclASol. Novaliq. https://www.novaliq.com/products/cyclasol/ . Accessed June 10, 2022.
  5. Novaliq Announces Positive Topline Results for Second Phase 3 Trial (Essence-2) of CyclASol in Dry Eye Disease. Novaliq. Dec. 21, 2021. https://www.novaliq.com/press-releases/2021/12/21/novaliq-announces-positive-topline-results-for-second-phase-3-trial-essence-2-of-cyclasol-in-dry-eye-disease/ . Accessed June 10, 2022.
  6. A Study to Confirm the Efficacy and Safety of K-161 Ophthalmic Solution for Treatment of Moderate to Severe Dry Eye Disease. ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT05403827 . Accessed June 10, 2022.
  7. A Study Assessing the Safety, Efficacy, and Optimum Dosage of K-161 in Subjects With Moderate to Severe Dry Eye Disease. ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT04084483 . Accessed June 10, 2022.
  8. Aldeyra Therapeutics Announces Positive Top-Line Data from Phase 2 Dry Eye Chamber Clinical Trial of Reproxalap, an Investigational New Drug, Compared to Xiidra. Aldeyra Therapeutics. Jan. 11, 2022. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-announces-positive-top-line-data-phase-2#:~:text=About%20Aldeyra%20Therapeutics&text=Reproxalap%20is%20in%20Phase%203,asthma%2C%20and%20COVID%2D19 . Accessed June 10, 2022.
  9. Aldeyra Therapeutics Announces Top-Line Results from the Phase 3 TRANQUILITY Trial in Dry Eye Disease. Aldeyra Therapeutics. Dec. 20, 2021. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-announces-top-line-results-phase-3 . Accessed June 10, 2022.
  10. Aldeyra Therapeutics Achieves Primary Endpoint in Phase 3 TRANQUILITY-2 Trial in Dry Eye Disease and Intends to Submit New Drug Application for Symptoms and Three Sign Endpoints of Dry Eye Disease. Aldeyra Therapeutics. June 8, 2022. https://ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-achieves-primary-endpoint-phase-3 . Accessed June 10, 2022.
  11. Seikagaku Initiates a Phase III Clinical Study for SI-614, a Therapeutic Agent for Dry Eye, in the U.S. Seikagaku Corporation. May 13, 2022. https://www.seikagaku.co.jp/en/news/news-511580783500892375/main/0/link/20220513e.pdf . Accessed June 10, 2022.
  12. Mitotech to Host Key Opinion Leader Webinar on Visomitin: A Potential Treatment for Dry Eye Disease. Mitotech SKQ. Jan. 26, 2022. https://www.mitotechpharma.com/news/mitotech-to-host-key-opinion-leader-webinar-on-visomitin-a-potential-treatment-for-dry-eye-disease/ Accessed June 10, 2022.
  13. Visomitin: A cardiolipin peroxidation inhibitor. Mitotech SKQ. https://www.mitotechpharma.com/technology/ Accessed June 10, 2022.
  14. Clinical Programs. Mitotech SKQ. https://www.mitotechpharma.com/programs/ . Accessed June 10, 2022.

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