Eyeworld

SUMMER 2025 | EYEWORLD | 49 C he said, adding that the side effect profile is negligible. The fascinating thing about the aldehyde species is there's a specific biomarker, malond- ialdehyde, which is elevated in the tears of dry eye patients, he said. With steroids, there are so many different biomarkers, and with lifitegrast, there's not a true biomarker. In April, Aldeyra Therapeutics announced that the FDA issued a complete response letter to the company's resubmission of a New Drug Application for reproxalap. In the letter, the FDA stated that reproxalap "failed to demonstrate efficacy in adequate and well controlled studies in treating ocular symptoms associated with dry eyes," advising "at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symp- toms of dry eye" be completed. The company's press release regarding the response noted FDA concerns with the data from the trial that could affect interpretation of the results. The letter did not find any manufacturing or safety issues with reproxalap, according to the company. Aldeyra expects to have a Type A meeting with the FDA to discuss the complete response letter and on- going clinical trials of reproxalap for dry eye. SkQ1 (Visomitin, Mitotech) Another interesting drug is SkQ1, Dr. Sheppard said, which is available in Russia. It's a broad-spectrum agent and has several metabolic effects. The effect on the eye is broad based because metabolic changes can occur in every cell phenotype on the ocular surface. "By enhancing mitochondrial metabolism and reducing inflammation, we can achieve notable sign and symptom improvements in dry eye disease," he said. The product is still in trials in the U.S. "I think the FDA approval rigors are guiding the endpoints," Dr. Sheppard said. "We're optimistic that the clinical trial design will prove the worth of this mechanism of action, which is different from other products on the market." He added that the MOA is fascinating because it's used in animal models for obesity, and it seems to have a persistent effect. Currently, a Phase 3 trial is in the works. Acoltremon (Alcon) At the end of May, Alcon announced FDA approval for acoltremon ophthalmic solution 0.003% under the name TRYPTYR for treatment of the signs and symptoms of dry eye disease. Dr. Starr said that acoltremon, a topical TRPM8 agonist, is a novel MOA via ocular surface cold thermoreceptors. It works quickly compared to many currently available immunomodulators, with significant increases in Schirmer's scores seen at 2 weeks compared to vehicle. Due to its unique MOA, it will be interesting to see if there is an off-label role for patients with chronic ocular pain and other corneal nerve disorders, he said. Dr. Gupta said that as a TRPM8 agonist, acoltremon activates the trigeminal nerve to stimulate tear production. While there have been other products to physically stimulate the nerve, this a different way to access the trigemi- nal nerve to stimulate tear production. Dr. Sheppard noted that TRPM8 receptors detect subtle temperature drops, even between blinks, and because these are cold-sensing stimulation receptors, they can be involved with neuropathic pain. This is a uniquely customized category, he said. AZR-MD-001 (selenium sulfide, Azura) According to the product description from the company, AZR-MD-001 "harnesses the power of selenium sulfide (SeS2) in an ophthalmic ointment preparation applied directly to the meibomian glands in the lower eyelid." It is transferred to the meibomian glands in the upper eyelid when the patient blinks. Dr. Starr called this product "very promis- ing," as there is no currently approved disease modifying medications for MGD. By reducing keratin and biofilms on the lid margin and within the meibomian gland ducts, we can improve meibum quantity and quality and the overall health of the meibomian glands, he said. This will be a welcome synergistic complement to procedural treatments like microblepharoex- foliation, intense pulsed light therapy, thermal continued on page 50

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