Bristol-Myers Squibb (Japan)

Ozanimod hydrochloride (Product name: ZEPOZIA® Capsule Starter Pack, ZEPOZIA® Capsules 0.92 mg; Nonproprietary name: ozanimod hydrochloride, hereinafter referred to as ozanimod) is an orally available receptor modulator that acts on the sphingosine 1-phosphate (S1P) receptor and selectively binds with high affinity to S1P1 and S1P5 receptors. Following binding to and activation of S1P1 receptors, ozanimod acts as a functional S1P1 receptor antagonist by inducing internalization of S1P1 receptors expressed on the surface of cells such as lymphocytes through agonism of S1P1 receptors. These effects may ameliorate the pathologic changes of the autoimmune disease ulcerative colitis (UC). The Japanese phase II/III study (Study RPC01-3103) demonstrated the efficacy and safety of this drug in Japanese patients with moderate to severe ulcerative colitis. In Japan, it was approved by the Ministry of Health, Labour and Welfare (MHLW) in December 2024 for the treatment of moderate to severe UC in patients who have had an inadequate response to conventional therapies, and was launched in March 2025. Existing UC treatments show significant therapeutic effects, but medications for moderate to severe UC have respective advantages and disadvantages in efficacy, safety, and administration routes. No treatment meets all criteria. Ozanimod, with a novel mechanism, offers sustained high efficacy in improving clinical symptoms and mucosal damage in moderate to severe UC patients. It has a favorable safety profile, high medication compliance, and is a convenient oral treatment for long-term use. Thus, providing Ozanimod as a new UC treatment option is of high clinical significance.

Background and AimsOzanimod is a once-daily, oral, selective sphingosine 1-phosphate receptor 1 and 5 modulator. The objective of the randomized, phase 2/3 J-True North study (NCT03915769) was to assess the efficacy and safety of ozanimod in Japanese patients with moderately to severely active ulcerative colitis.MethodsIn the 12-week induction period (IP), patients were randomized 1:1:1 to receive placebo, ozanimod 0.46 mg, or ozanimod 0.92 mg. Patients who completed the IP with a clinical response at week (w) 12 were eligible to enter a 40-week maintenance period where they received the same treatment as they did in the IP. The primary endpoint was clinical response (complete Mayo score) at w12; clinical and mucosal secondary endpoints were assessed at w12 and w52.ResultsOf 198 patients randomized, 176 completed the IP. Of these patients, 97 entered and 77 completed the maintenance period. A significantly higher proportion of patients receiving ozanimod achieved clinical response at w12 versus placebo (ozanimod 0.46 mg: 52.9%, P = .0158; ozanimod 0.92 mg: 61.5%, P = .0006; vs placebo: 32.3%). Similar results were observed in the secondary endpoints where patients receiving ozanimod achieved higher rates of clinical remission, endoscopic improvement, and mucosal healing at w12 than those receiving placebo. Efficacy was maintained at w52 for all endpoints. Both doses of ozanimod were well tolerated, with no unexpected safety signals.ConclusionThis large-scale clinical trial demonstrated the efficacy and safety of once-daily oral ozanimod in Japanese patients with moderately to severely active ulcerative colitis. This is the first time that the efficacy and safety of ozanimod were verified in a large number of patients in Asia.

BackgroundThe aims of this study were to gather expert agreement about essential aspects of clear aligner therapy (CAT) and to determine what research areas need further investigation.Materials and methodsA steering committee performed literature selection and compiled a list of 25 statements. This study used a modified Delphi method involving a panel of 23 international orthodontic experts. Six essential areas of CAT were investigated: treatment efficacy, quality of life, side effects, management of growing patients, treatment with extraction, and treatment of periodontal patients. A panel of experts assessed 25 statements using a 5-point Likert scale throughout 3 rounds of the study. A steering committee adjusted statements that failed to achieve consensus through either revision, splitting, merging, or complete removal.ResultsAfter the third round, 22 statements achieved consensus while 3 statements were rejected. The panel agreed that aligners could be used effectively in some types of malocclusions, such as those with mild or moderate crowding or open bite cases. The experts reached a consensus on the biomechanical limits of clear aligners. However, they agreed on the benefits in terms of improved quality of life during treatment and easier maintenance of oral hygiene maneuvers. Regarding specific patient categories, the panelists supported the use of aligners in periodontal patients with tooth migration requiring tipping movements. They also agreed on the advantages of using a rapid palatal expander over aligners in growing patients.ConclusionsThe panel members reached agreement on most topics. However, they acknowledged limitations in the current literature regarding root resorption and orthodontic relapse with CAT compared to fixed appliances. The absence of agreement on treatment duration, effects on skeletal growth, and the management of periodontally compromised patients highlights significant evidence gaps that warrant further research.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40510-025-00575-1.

To identify factors affecting the health-related quality of life (HR-QOL) of symptomatic patients with hypertrophic cardiomyopathy (HCM) using qualitative interviews exploring patients' experiences and perceptions. This cross-sectional observational study was conducted using qualitative web-based or telephone interviews. Adult patients with HCM in Japan who were experiencing burden because of HCM were included. In-depth interviews were conducted using a semi-structured interview guide. The data were analyzed using a thematic analysis approach. Nineteen patients completed the interview. Ten HR-QOL-related themes were identified. Many patients were unaware that they had HCM symptoms, either no longer noticing them following life adjustments or attributing them to factors other than HCM. HCM affected multiple life aspects, including work, family, and social life. Patients resisted disclosing their disease to others and strongly resisted invasive treatment. Patients highly trusted their physicians but were reluctant to discuss their mental burdens and daily life challenges with them. This first qualitative study of HR-QOL in patients with HCM in Japan suggests that deeper physician - patient communication is needed to understand patient burden and needs, as patients have difficulty discussing their burdens with physicians and may lack awareness of HCM symptoms. NCT06181617 (ClinicalTrials.gov).

Luspatercept has shown durable clinical efficacy for the treatment of anemia in transfusion-dependent patients with lower-risk myelodysplastic syndromes (LR-MDS). We report the results of a prespecified primary analysis of a phase 2 trial of luspatercept in non-transfusion-dependent (NTD) Japanese patients with anemia due to LR-MDS. Luspatercept (starting dose 1.0 mg/kg) was administered subcutaneously once every 3 weeks. The primary endpoint was the proportion of patients who achieved hematological improvement-erythroid (HI-E) response (≥ 1.5 g/dL increase in hemoglobin level for 8 weeks) without transfusions within the first 24 weeks of treatment. At the primary analysis data cutoff, 21 patients had been enrolled/treated; 17 and 10 patients had completed 24 and 48 weeks of treatment, respectively. HI-E response occurred within 24 weeks in 10 patients (47.6%; 95% confidence interval, 25.7–70.2; P < 0.0001), which was significantly higher than the predefined threshold (10%). By week 48, HI-E response occurred in 12 patients (57.1%) and 17 patients (81.0%) remained NTD. Luspatercept was well tolerated. Three patients (14.3%) had grade 3–4 treatment-related treatment-emergent adverse events. Luspatercept resulted in statistically and clinically significant improvements in hemoglobin levels, and may help delay the need for transfusions in NTD patients with LR-MDS.