Vevye brings new meaning to tolerability for patients.
When assessing molecular versatility, cyclosporine is tough to beat. An anti-inflammatory agent, the drug is utilized for a variety of conditions and has taken on various iterations. Cyclosporine exists as a solution, an ointment and an emulsion. It has been preserved, non-preserved, unit-dosed and multi-dosed. It’s been mixed in corn oil, peanut oil, proprietary oil, cationic solutions and, now, a semifluorinated alkane (perfluorobutylpentane) in the form of Vevye, a new prescription drop from Harrow Inc.
The first and only cyclosporine-based product indicated for the signs and symptoms of dry eye disease (DED), Vevye received FDA approval in June 2023 and has been available since January 2024. For ophthalmologists, the drug represents another option in an evolving and growing assortment of DED medications.
“Cyclosporine’s history really is remarkable,” says Dr. Richard A. Adler, MD, FACS, director of ophthalmology at Belcara Health, Baltimore. “There have been many innovations in its formulation, and each version continues to add value.”
As more is learned about chronic DED, cyclosporine has brought more improved drug effectiveness, explains Dr. Adler, who has been prescribing the medication since its launch in January. “Vevye has been designed to optimize three opportunities in the current DED therapeutic marketplace: bioavailability, improved speed of onset and improved tolerability. It’s a first-in-class, novel formulation of an already well-established treatment option.”
IMPORTANT FIRSTS, EXPANDED BENEFITS
A combination of a 0.1% cyclosporine solute and a semifluorinated alkane with no associated pH or osmolarity, and no water, Vevye is administered twice daily in 10-microliter-sized drops. With perfluorobutylpentane as the vehicle of delivery, Vevye makes cyclosporine highly bioavailable, according to clinical data, says Mark L. Baum, chief executive officer and founder at Harrow. “Research shows that Vevye delivers into the cornea up to 22 times more cyclosporine than other products can,” says Mr. Baum.
He adds that experts widely believe that all forms of chronic DED, whether it be evaporative, aqueous deficient, or any other way to divide the market, have an inflammatory component — meaning DED equals inflammation. “The ability to deliver a high concentration of cyclosporine in a tolerable way is unique to our product,” he says. “And when you can deliver a disease-modifying active ingredient in this concentration, numerous amazing things can happen.”
Findings from a 52-week extension study that followed a 4-week pivotal study showed participants experienced improved tear production by 98%, on average, and significantly reduced corneal staining as early as Week 2. Importantly, 99.8% of patients reported no, or only mild, stinging/burning upon administration. Only one subject dropped out of the study due to mild burning and stinging.
Three randomized studies involving nearly 1,400 subjects have shown that the majority of patients treated with Vevye experience clinically and statistically significant improvement in corneal staining or healing by Day 15. With cyclosporine previously targeting increased tear production, the indication for DED signs and symptoms expands the known value of cyclosporine, Dr. Adler notes. He also believes that utilizing perfluorobutylpentane offers an advantage over other semifluorinated alkane options.
“It has superior solubility,” explains Dr. Adler. “Cyclosporine dissolves better in perfluoro-butylpentane than it does in perfluorohexyloctane, which has been used in other drops and, therefore, this semifluorinated alkane serves as an excellent carrier for the active drug.” Another intriguing characteristic is that, as an anhydrous product, there is little opportunity for bacteria to grow, eliminating the need for added preservatives. “Additionally, because the cornea itself is lipophilic, it doesn’t play well with water,” says Dr. Adler. “The absence of water in this formulation may permit cyclosporine to penetrate well in a smaller drop size.”
THE TOLERABILITY ISSUE
As more patients are introduced to this medication, Dr. Adler believes tolerability will stand out to physicians. “Tolerability has been an issue with almost all dry eye drops, and probably the main reason for poor patient adherence,” he says. “Larger drops can contribute to tolerability issues. Additionally, Vevye has low surface tension, which improves spreadability and residence time on the cornea. Studies show that the drop demonstrates rapid penetration with high concentrations of cyclosporine observed in the cornea within the first hour of administration.”
As such, patients with tolerability issues will be especially well suited, says Laura M. Periman, MD, founder and director of dry eye services and clinical research at Periman Eye Institute, Seattle. “I’m reaching for Vevye for patients who have tried and failed other immunomodulators because of tolerability concerns, whatever the challenge might be,” says Dr. Periman, who has been prescribing the medication since its approval. “With Vevye, we have another formulation option against dry eye, which is good news for patients because tolerability is not guaranteed with any formulation. To have a different delivery system gives patients the opportunity to take another run at an effective long-term immunomodulator.”
Dr. Adler echoes that sentiment, noting that the expanding number of cyclosporine formulations continues to reveal that there are potentially many options for each patient. “This drop has a fast onset of action and excellent tolerability, but we should continue to view innovations such as Vevye as an addition, not a replacement, for the growing number of effective therapeutics,” he says. “We are fortunate to practice eye care in a time when there are many scientifically sound options to manage DED.”
PATIENT EDUCATION
To maximize the benefits of Vevye, Dr. Periman conducts chair-test-dosing because there is a learning curve to application. “It comes in a tiny bottle because the effective drop volume is one-fifth what you’re accustomed to with water-based eyedrops,” she says.
So, some teaching is required for the patient to squeeze the bottle correctly. When seated, Dr. Periman suggests that patients hold the bottle upright and to squeeze slightly before inverting the bottle overhead and squeezing slightly again to release the drop. Patients with manual dexterity concerns or limited mobility require more instruction.
PATIENT ACCESS AND REIMBURSEMENT
Mr. Baum is encouraged about what he says is an increasing number of formularies that include Vevye; however, an established access program ensures that the price maxes out at $79 per patient. “The payors are recognizing the promise of this product,” he says. “Our company was founded on the principle of access and affordability. We buy down co-pays. And nobody has done this before, but if a patient pays for our product and is not satisfied, we will refund them the full cost. If providers entrust patients to us, we’re going to partner with them to make sure patients get their prescription, and we will refund their payment if they don’t like the results.” OM
