The Phase 3 Study Results of Varenicline Solution Nasal Spray for The Treatment of Dry Eye Disease in Chinese Patients Was Published in The Lancet

SHANGHAI, China, March 8 , 2024 – Ji Xing Pharmaceuticals Limited (JIXING), a clinical-stage biopharmaceutical company committed to bringing innovative medicines to underserved Chinese patients with serious and life-threatening diseases, announced that the Phase 3 clinical trial results of varenicline solution nasal spray for the treatment of signs and symptoms of dry eye disease in Chinese patients have been published in The Lancet Regional Health - Western Pacific, a subset of The Lancet, one of the top four international journals. This is the first national multicenter, randomized, controlled, double-masked Phase 3 clinical study to stimulate natural tear production through a nasal spray formulation in China, as well as the first time the report of its clinical study for the treatment of dry eye patients has been published in The Lancet, one of the world's leading academic journal groups.

Tear film instability is a central pathophysiological mechanism in the development of dry eye, of which tear deficiency is an important cause of reduced tear film homeostasis. Therefore, increasing the patient's natural tear production can improve tear film stability.

As a highly selective cholinergic agonist, varenicline solution nasal spray is designed to activate the trigeminal parasympathetic pathway resulting in increased natural tear production. In 2021, it was approved in the U.S. by the Food & Drug Administration (FDA) , as the first and only preservative-free, multi-dose, sterile-packaged nasal spray for the treatment of mild, moderate and severe dry eye diseases.

The Phase 3 clinical study, published in the Lancet subset, was designed as a multicenter, randomized, controlled, double-masked study to evaluate the safety and efficacy of varenicline solution nasal spray to treat signs and symptoms of dry eye disease. The study enrolled 340 subjects at 20 centers across China. The study found that varenicline solution nasal spray demonstrated clinically meaningful efficacy in dry eye disease when applied twice daily, while also maintaining a favorable safety and tolerability profile. Furthermore, varenicline solution nasal spray has an innovative delivery method that uses a preservative-free, multi-dose nasal spray to protect the ocular surface, giving dry eye patients a treatment option that is both effective and convenient.

“Through a nasal spray formulation, varenicline solution nasal spray significantly improves natural tear production and can interrupt the vicious cycle of dry eye pathophysiology by stabilizing the tear film. And it also avoids the cumbersome use of traditional eye drops.” said Professor Ying Jie, Principal Investigator of the varenicline solution nasal spray Phase 3 study in China, Director of Ophthalmology Institute at Beijing Tongren Hospital Affiliated to Capital Medical University. “I am delighted that this research has been published in The Lancet subset, further supporting the treatment of varenicline solution nasal spray on dry eye patients in China. I believe that this innovative therapy may be a paradigm-changing way to treat dry eye disease and will bring new treatment options to clinicians and dry eye patients.”

" The publication of the Phase 3 clinical study of varenicline solution nasal spray in China in an internationally renowned academic journal is the culmination of the sincere cooperation between JIXING's R&D team and domestic and international experts, and also fully recognizes the level of clinical research in China. " said Larry Li, MD, PhD, Chief Medical Officer of Ophthalmology at JIXING. "The clinical study results provide high-level evidence-based medical evidence for the full approval and clinical application of innovative dry eye therapy in China. Now we are actively promoting the approval process of preservative-free varenicline solution nasal spray in China, and look forward to benefiting more Chinese dry eye patients with this treatment as soon as possible."

In February 2023, Varenicline solution nasal spray was approved in Macao SAR, and since April 2023, it has been available in Boao Lecheng International Medical Tourism Pilot Zone as an imported drug for patients with urgent clinical needs. In July 2023, the new drug application was formally accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the PRC. In December 2023, it was prescribed for the first time in the Greater Bay Area at the University of Hong Kong - Shenzhen Hospital.

Full article link: https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(24)00026-9/fulltext

About Varenicline solution nasal spray

Varenicline solution nasal spray (US brand name TYRVAYA?) is a highly selective cholinergic agonist that is U.S. FDA approved to treat signs and symptoms of dry eye disease as a multidose nasal spray. The parasympathetic nervous system controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose. The efficacy of varenicline solution nasal spray in dry eye disease is believed to be the result of varenicline's activity at heteromeric sub-type(s) of the nicotinic acetylcholine (nACh) receptor where its binding produces agonist activity and activates the trigeminal parasympathetic pathway resulting in increased production of basal tear film as a treatment for dry eye disease. Varenicline binds with high affinity and selectivity at human α4β2, α4α6β2, α3β4, α3α5β4 and α7 neuronal nicotinic acetylcholine receptors.

TYRVAYA? is a registered trademark of Oyster Point Pharma, Inc., a Viatris company.

About China Phase 4 Clinical Study for Varenicline solution nasal spray

The China Phase 3 clinical study was designed as a multicenter, randomized, controlled, double-masked study to evaluate the safety and efficacy of varenicline solution nasal spray for the signs and symptoms of dry eye disease. The study enrolled 340 subjects at 20 centers in China and investigated varenicline solution nasal spray (0.6 mg/ml), as compared to control (vehicle) nasal spray. Subjects were administered varenicline solution nasal spray twice daily for 4 weeks. The study results demonstrated efficacy and safety profiles consistent with previous studies.

The study met the primary efficacy endpoint. Comparing to the control group, varenicline solution nasal spray showed a statistically significant and clinically meaningful improvement in natural tear production at week 4. In the varenicline solution nasal spray group, the percentage of subjects gaining >10mm on Schirmer’s test score (used to evaluate tear production) was 36% as compared to 18% in the control group (p=0.0002 vs. control). The stratified odd ratio was 2.7 in the varenicline solution nasal spray group vs. the control group.

For the secondary efficacy endpoint, compared to the control group, the mean change of Schirmer's test score in the varenicline nasal spray group at week 4 showed statistically significant and clinically meaningful improvement. In addition, the mean Eye Dryness Score (used to assess the improvement of dry eye symptoms) at week 4 also improved significantly from baseline.

Varenicline solution nasal spray was well-tolerated in the Chinese population. The most common adverse event experienced in the treatment group was sneezing. Overall, sneezing was mild, transient and resolved without intervention (most sneezing occurred within the first minute after dosing and stopped within 1 minute). There were no reports of serious adverse events related with nasal administration. The number of subjects with treatment emergent adverse events related to study drug leading to discontinuation was 0.6% or less in either treatment group.

About JIXING

JIXING is a biopharmaceutical company headquartered in Shanghai committed to bringing innovative science and medicines to underserved patients in China and around the world with serious and life-threatening diseases. Backed by RTW Investments, LP, JIXING was founded in 2019 and partners with global biotechnology companies to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in cardiovascular and ophthalmic diseases. With a strong and further developing asset pipeline, seasoned management team, and patient-centric focus, JIXING is dedicated to delivering a meaningful and lasting impact on patients in China and around the world.

JIXING’s cardiovascular portfolio includes 5 assets in late-stage clinical development (Aficamten, Etripamil, Omecamtiv Mecarbil，JX09 and JX10). JIXING’s ophthalmology portfolio includes 4 assets in late-stage clinical development (varenicline solution nasal spray/US brand name TYRVAYA, OC-02 nasal spray, JX06/LNZ100, JX07/LNZ101) and 1 asset in pre-clinical stage (JX08).