SAT0164 MC2-03 (CICLOSPORIN EYEDROPS) IMPROVES TEAR PRODUCTION IN SJÖGREN’S PATIENTS WITH MODERATE-TO-SEVERE KERATITIS: RESULTS FROM A PHASE 2B RANDOMIZED, CONTROLLED TRIAL

Background: Sjogren Syndrome (SS) is a multifaceted disease with variable symptoms, but the SS associated keratoconjunctivitis is one of the most frequent disease manifestations of the syndrome and the manifestation that has the greatest impact on the quality of life for these patients. Objectives: To report the clinical efficacy of MC2-03 eyedrops in Sjogren’s patients with moderate-to-severe keratitis from a 6-month trial looking at the Schirmer score which assess the tear production by the lacrimal gland. A Schirmer score of ≤5mm/5 min is one of the criteria used in the 2016 final classification of ACR/EULAR to diagnose Sjogren`s syndrome. Methods: The NORTHERN LIGHTS trial is a randomized, double masked, controlled multicentre European trial that assessed MC2-03 eyedrops (ciclosporin 0.03% and 0.06%) for the treatment of moderate-to-severe dry eye disease in 255 patients having corneal fluorescein staining score 3 or 4 at baseline. The Schirmer score (per 5 min) was assessed during this trial. A total of 66 patients (25.9%) with medical history of Sjogren’s syndrome were randomized in the trial. Results: Demographics and baseline disease characteristics were comparable between treatment arms: mean age 60.4 years, 90.9% were females (n=60) and the mean Schirmer score in the worst eye was ~3mm (2.8mm – 3.2mm, except for the vehicle, mean Schirmer score of 5.5mm). The mean Schirmer score improved rapidly from baseline to month 1 for MC2-03 0.03% eye drops (+2.4mm) reaching statistical significance versus vehicle (-0.5mm, p=0.028) and lubricant therapy (-0.6mm, p=0.020). This improvement was maintained at month 6 where the change was +2.5mm for MC2-03 0.03% eye drops compared to -1.1mm for vehicle (p=0.028). Statistical significance was also achieved at Month 6 comparing the higher strength MC2-03 0.06% eye drops (+2.8mm) to vehicle (-1.1mm, p=0.005) and lubricant alone (-0.5mm, p=0.009). Three in eleven (27.3%) Sjogren`s patients treated with MC2-03 0.03% eye drops improved from a diagnostically low Schirmer ≤5mm at baseline (10/12, 83.3% ≤5mm) to Schirmer >5mm at month 3 and month 6 (6/11, 54.5% ≤5mm), while on the other hand 1 in 14 (7.1%) patients worsened in the vehicle group. A similar response was seen for MC2-03 eye drops 0.06%. For Sjogren´s patients with Schirmer ≤5mm at baseline, a greater proportion of patients improved ≥3mm at month 6 when treated with MC2-03 eye drops 0.03% (44.4%, 4/9) and 0.06% (53.8%, 7/13) compared to vehicle (0%, 0/9) and lubricant (7.7%, 1/12). At month 6, a statistically significantly higher proportion of patients achieved clinically meaningful improvements in both corneal staining (≥2 grades improvement) and Schirmer score (≥3mm/5 min) when treated with MC2-03 0.03% eye drops (45.5%, 5/11) compared to both vehicle (0%, 0/14, p=0.009) and lubricant (0%, 0/15, p= 0.007). A higher number of patients treated with MC2-03 0.06% was observed without statistical significance. Conclusion: MC2-03 eye drops once daily rapidly increased tear production and further improved corneal staining in Sjogren´s patients with moderate to severe keratitis, which both are objectives included as diagnostic criteria for Sjogren’s disease. MC2-03 eye drops were well tolerated with no unexpected safety findings. Disclosure of Interests: : Frederic Gomez Consultant of: MC2 Therapeutics, Morten Praestegaard Employee of: MC2 Therapeutics, Johan Selmer Employee of: MC2 Therapeutics, Jutta Horwath-Winter Consultant of: CromaPharma, Omnivision, MC2 Therapeutics, Speakers bureau: Allergan, Bausch&Lomb, Cromapharma, Ursapharma, Thea, TRB-Chemedica, Santen, Maite Sainz de la Maza: None declared, Steffen Heegaard Consultant of: Sanofi, MC2 Therapeutics, Speakers bureau: Santen, Sanofi, Thea, Leo