July 18, 2023
NASHVILLE, Tenn. and HEIDELBERG, Germany — Harrow and Novaliq GmbH announced an agreement under which Harrow will acquire the U.S. and Canadian commercial rights for VEVYE (cyclosporine ophthalmic solution) 0.1%, a patented, non‑preserved, ophthalmic solution prescription drug based on Novaliq’s proprietary EyeSol water-free technology. VEVYE, which is dispensed topically in a unique 10 microliter per one drop, and is labeled for twice‑daily (BID) dosing, is the first and only cyclosporine-based product indicated for the treatment of both signs and symptoms of dry eye disease (DED). VEVYE was approved on May 30, 2023, by the U.S. Food and Drug Administration (FDA).
In commenting on the transaction, Mark L. Baum, Chairman and Chief Executive Officer of Harrow, said, “The acquisition of the U.S. and Canadian commercial rights to VEVYE demonstrates our commitment to the highly underserved dry eye and ocular surface inflammation markets. We are particularly excited about adding VEVYE to our portfolio because of our strong belief that the U.S. DED market is in need of a cyclosporine‑based product that is generally well tolerated, improves both the signs and symptoms of DED and, critically, reduces the time it takes for patients to experience relief from this all-too-common and, in many cases, debilitating disease. VEVYE not only feels better in the eye, but it performs differently, and we believe it addresses the numerous unmet needs in the large and growing U.S. DED market. We look forward to making VEVYE available in the U.S. later this year.”
Christian Roesky, Ph.D., Chief Executive Officer of Novaliq, stated, “We are excited to partner with Harrow, one of the fastest growing and most dynamic ophthalmic pharmaceutical companies in the U.S., to commercialize VEVYE in the U.S. and Canadian markets. Harrow and its commercial team have a distinguished track record for successfully commercializing new and clinically important pharmaceutical products in the U.S. market, and they specifically have many years of experience successfully marketing cyclosporine-based formulations to U.S. eye care professionals. The Novaliq team looks forward to supporting Harrow during the launch of VEVYE, a truly unique and powerful new treatment option for U.S. eye care professionals and the more than 16 million Americans who have been diagnosed with DED.”
VEVYE Clinical Data
The safety and efficacy of VEVYE (development name: CyclASol) for the treatment of dry eye disease were assessed in a total of 1,369 patients with dry eye disease, of which 738 received VEVYE.
Study CYS-001 (NCT02113293) was the first-in-human study and was conducted to investigate the safety, tolerability, and pharmacokinetics (PK) in healthy volunteers. In this study, VEVYE was shown to be safe, and no systemic exposure of cyclosporin was observed after ocular administration.
Study CYS-002 (NCT02617667, Wirta et al 2019) demonstrated that VEVYE-dosed patients showed a statistically significant early and clinically meaningful increase in Schirmer’s tear test score at Day 29 compared to vehicle. Additionally, VEVYE showed greater improvement in corneal and conjunctival staining compared to (i) vehicle and (ii) Restasis over the four-month treatment period. The favorable safety and tolerability profile of VEVYE was confirmed.
Study CYS-003 (ESSENCE-1; NCT03292809, Sheppard et al 2021) confirmed the effects seen in CYS-002. Compared to vehicle at the end of treatment, there was a statistically significant higher percentage of patients with increases of ≥10 mm from baseline in Schirmer’s tear test score at Day 85. Notably, the study demonstrated statistically significant reduction in total, central corneal fluorescein and conjunctival staining scores favoring VEVYE at all time points, in addition to VEVYE meeting the primary endpoint of the study. 52.9% of patients responded within four weeks with a clinically meaningful improvement of ≥3 grades in total corneal staining, which was significantly higher compared to vehicle. Responders showed statistically significant improvements in a variety of symptoms compared to non-responders. VEVYE was safe, well tolerated, and comfortable over the three-month treatment duration.
Study CYS-004 (ESSENCE-2; NCT04523129, Akpek et al 2023) was designed to replicate CYS-003 and met the primary corneal staining endpoint. In this study, 71.6% of patients responded within four weeks with a clinically meaningful improvement of ≥3 grades in total corneal staining. Again, responders showed statistically significant improvements in a variety of symptoms compared to non-responders at Day 29. Subjects with high central corneal staining at baseline were shown to benefit from VEVYE with statistically significant improvements in their blurred vision score compared to vehicle CYS-004 studies as shown in CYS-003. Schirmer’s tear test responses of ≥10 mm increase was statistically significantly higher in the VEVYE compared vehicle at Day 29. VEVYE was safe, well tolerated, and comfortable over the one-month duration.
Study CYS-005 (NCT04523142, Wirta et al 2023) was an open label extension study of CYS-004. VEVYE was shown to be safe and well tolerated during long-term use over 12 months. Sign and symptom endpoints continued to improve over the course of the study demonstrating sustained efficacy over 52 weeks of therapy in both signs and symptoms.
1. Wirta DL, Torkildsen GL, Moreira HR, Lonsdale JD, Ciolino JB, Jentsch G, Beckert M, Ousler GM, Steven P, Krösser S. A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease. Ophthalmology. 2019; 126:793-800
2. Sheppard JD, Wirta DL, McLaurin E, Boehmer BE, Ciolino CB, Meides AS, Schlüter T, Ousler GW, Usner D, Krösser S. A Water‑free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase II/III ESSENCE Study. Cornea. 2021; 40:1290-1297
3. Akpek EK, Wirta DL, Downing JE, Tauber J, Sheppard JD, Ciolino JB, Meides AS, Krösser S: Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial. JAMA Ophthalmology. 2023; 141(5):459-466.
4. Wirta DL, Krösser S, Long -Term Safety and Efficacy of a Water-Free Cyclosporine Ophthalmic Solution for the Treatment of Dry‑Eye Disease: ESSENCE-2-OLE study. ASCRS 2023 paper presentation.
Adverse Reactions
Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials with 738 subjects receiving at least 1 dose of VEVYE, the most common adverse reactions were instillation site reactions (8%) and temporary decreases in visual acuity (3%).
