JIXING Announces Positive Topline Results from China Phase 3 Study for Ophthalmology Product Varenicline Solution Nasal Spray
Varenicline solution nasal spray met the primary efficacy endpoint for the treatment of signs and symptoms of dry eye disease in adult patients
Varenicline solution nasal spray demonstrated an efficacy and safety profile consistent with previous studies
The positive topline results support a New Drug Application in China
SHANGHAI, China, July 18, 2023 – 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, today announces positive topline results from the China Phase 3 Study for varenicline solution nasal spray (US brand name TYRVAYA®) for the treatment of signs and symptoms of dry eye disease in adult patients. This is the first Phase 3 study for the treatment of dry eye disease by stimulating natural tear production through a nasal spray formulation in China.
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 to treat signs and symptoms of dry eye disease. The study enrolled 340 subjects at 20 centers across China. The study met the pre-defined primary efficacy endpoint at Week 4 with varenicline nasal spray showing a statistically and clinically significant improvement in natural tear production as compared to baseline (the percentage of subjects gaining ≥10 mm in Schirmer’s test score). Additionally, the study produced positive results for a number of secondary efficacy endpoints. Overall, it demonstrated efficacy and safety profiles consistent with previous studies.
“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. Increasing the patient's natural tear production will therefore improve tear film stability. As the first Phase 3 study for the treatment of dry eye disease stimulating natural tear production through a nasal spray formulation in China, the positive topline results announced today are very encouraging.” said Professor Ying Jie, Principal Investigator of the varenicline solution nasal spray Phase 3 study in China, Director of Corneal Disease Center and Deputy Director of Ophthalmology Institute at Beijing Tongren Hospital Affiliated to Capital Medical University. “Through a nasal spray formulation, varenicline solution nasal spray avoids the cumbersome use of traditional eye drops. It significantly improves natural tear production and can interrupt the vicious cycle of dry eye pathophysiology by stabilizing the tear film. The study results demonstrated that varenicline solution nasal spray may be a paradigm-changing way to treat dry eye disease and will bring new treatment options to clinicians and dry eye patients.”
“This is the first Phase 3 clinical study completed by JIXING in China and we thank all the investigators and patients for their participation and contribution to this study. The success of the study demonstrates both the confidence in varenicline solution nasal spray by the investigators and patients, and the academic capability of JIXING ophthalmology team.” said Larry Li, MD, PhD, Chief Medical Officer of Ophthalmology at JIXING.” The product demonstrated efficacy and safety profiles in Chinese patients which are consistent with previous studies. The topline results serve as evidence to support a New Drug Application in China.”
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.
Dry eye disease is a chronic condition that is estimated to impact more than 200 million patients in China and is growing in prevalence, significantly influencing a person’s day-to-day quality of life. It can cause persistent stinging, scratching, burning sensations, sensitivity to light, blurred vision, and eye fatigue. Dry eye disease is a multifactorial disease of the ocular surface characterized by disruption of the tear film. Human tear film is a complex mixture of more than 1,500 different proteins, including growth factors and antibodies, as well as numerous classes of lipids and mucins. Natural tear film protects and lubricates the eyes, washes away foreign particles, contains growth factors and antimicrobial components, and creates a smooth surface that forms the primary refractive surface of the eye. Despite the large prevalence and a significant disease burden, there remains a large unmet need in dry eye disease.
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.
JIXING is a biopharmaceutical company headquartered in Shanghai committed to bringing innovative science and medicines to underserved patients in China 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.
JIXING’s cardiovascular portfolio includes 3 assets in late-stage clinical development (Aficamten, Etripamil, Omecamtiv Mecarbil) and 1 in pre-clinical stage (JX09). 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). For further information about JIXING, please visit www.jixingbio.com.
- Wirta, D., Vollmer, P., Paauw, J., et al.& ONSET-2 Study Group. Efficacy and Safety of OC-01 (Varenicline) Nasal Spray on Signs and Symptoms of Dry Eye Disease: the ONSET-2 Phase 3, Randomized Trial. Ophthalmology 2021; -:1-9. https: //doi.org/10.1016/j.ophtha.2021.11.004.
- Wirta, D., Torkildsen, G. L., Boehmer, B., Hollander, D. A., Bendert, E., Zeng, L., ... & Nau, J. (2022). ONSET-1 phase 2b randomized trial to evaluate the safety and efficacy of OC-01 (varenicline solution) nasal spray on signs and symptoms of dry eye disease. Cornea.
- Market-Scope. 2020 Dry Eye Products Report: A Global Market Analysis for 2019 to 2025. October 2020.
- Uchino M., Schaumberg D.A. Dry Eye Disease: Impact on Quality of Life and Vision. Curr. Ophthalmol. Rep. 2013; 1:51–57. doi: 10.1007/s40135-013-0009-1.
- Tsubota K, Pflugfelder S, Liu Z, et al. Defining dry eye from a clinical perspective. Int J Mol Sci 2020; 21 (23):9271. doi: 10.3390/ijms21239271.
- Song P, Xia W, Wang M, et al. Variations of dry eye disease prevalence by age, sex, and geographic characteristics in China: a systematic review and meta-analysis. Journal of global health (2018); 8(2):020503. doi: 10.7189/jogh.08.020503.
- Liu, Ning-ning, et al. Prevalence of and Risk Factors for Dry Eye Symptom in Mainland China: A Systematic Review and Meta-Analysis. Journal of Ophthalmology (2014); 2014(3):748654–8.
- Jie Y, Xu L, Wu YY, Jonas JB. Prevalence of dry eye among adult Chinese in the Beijing Eye Study. Eye (Lond) (2009); 23(3):688-93.