Novartis (Japan)

IntroductionCanakinumab was approved in Japan for the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) in 2018, following an open-label, single-arm phase III study performed in 19 Japanese patients with sJIA. Given this limited sample size, Japanese regulatory authorities required an all-case post-marketing surveillance study as part of the approval conditions, aiming to assess the long-term safety and effectiveness of canakinumab in Japanese patients with sJIA in clinical practice and characterise the clinical course of any cases of macrophage activation syndrome (MAS).MethodsThis was a multicentre, central registration, all-case, uncontrolled, open-label, special drug use investigation, including all patients who received canakinumab for the treatment of sJIA between 2 July 2018 and 20 December 2024. Patients were treated according to the investigators’ routine clinical practice and observed for up to 104 weeks.ResultsThe safety analysis population included 125 patients with a median duration of treatment (including interruptions) of 710.0 (range 1–729) days and median total number of doses of 25.0 (range 1–29). Adverse events (AEs) occurred in 91 out of 125 patients (72.8%), with the most common being relapse, worsening or exacerbation of Still’s disease (24 patients, 19.2%), followed by upper respiratory tract inflammation (18 patients, 14.4%). Serious related AEs occurred in 22 patients (17.6%), with the most common being haemophagocytic lymphohistiocytosis (HLH; 5 patients, 4.0%). A total of ten MAS-related AEs were reported; all were cases of HLH and were considered serious, and all were resolved or were resolving at the time of reporting. Effectiveness outcomes, including glucocorticoid tapering, disease activity reduction and inflammatory marker normalisation, were durable through 2 years of treatment.ConclusionCanakinumab showed a favourable long-term safety profile and sustained effectiveness in Japanese patients with sJIA inadequately controlled by existing therapies. No new safety concerns emerged, and the safety profile was comparable to that observed in the earlier phase III study.

The management of hypertension is one of the most important public health issues. Many patients with untreated hypertension in Japan require urgent treatment. This retrospective cohort study in Hiratsuka city aimed to evaluate the proportion of participants achieving target blood pressure and identify modifiable factors affecting the achievement. We retrospectively analyzed data from a merged database of claims, specific health checkup (SHC), and national health insurance data in Hiratsuka City, Japan, from June 2016 to March 2023. The study participants were adults aged 40–74 years without a history of hypertension treatment and with blood pressure ≥140/90 mmHg at SHC. The primary outcome was the achievement of target blood pressure <140/90 mmHg at the next SHC. Furthermore, multivariable logistic regression was performed to explore factors influencing the achievement. Of 5428 participants, 43.6% were female. The median age was 69 years, and 58.4% (95% confidence interval 57.1–59.7) achieved target blood pressure <140/90 mmHg. Multivariable logistic regression results showed that achievement of target blood pressure was associated with younger age (50–69 years), mild hypertension (grade I), no hypertension at the previous SHC, no record of SHC in the previous year, and willingness to improve lifestyle. One-third of people reported that their hypertension at SHCs failed to achieve target blood pressure. For community-level hypertension management, people who have the influencing factors must be educated by public health nurses, which might be effective for lifestyle improvement. Additionally, the elderly and people with persistent hypertension or severe hypertension should seek medical advice.

ObjectiveThis prospective, open-label, single-arm, phase 2 study evaluated the efficacy, safety, pharmacokinetics (PK) and dosimetry of [177Lu]Lu-PSMA-617 in Japanese patients with progressive PSMA+ mCRPC.MethodsThis is a PK/dosimetry analysis of [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617 in patients from Parts 1, 2, and 3 of the 4-part study. Blood and urine samples, serial PET/CT, planar, and SPECT/CT scans were collected post-administration of [68Ga]Ga-PSMA-11 (111–259 MBq) at screening and [177Lu]Lu-PSMA-617 (7.4 GBq ± 10%) during cycle 1. External radiation exposure in medical personnel and family members was measured once in each cycle from cycle 1 to 6, excluding the cycle where dosimetry was performed.ResultsOf 35 patients included, 3 patients each had evaluable data for PK/dosimetry of [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617. Both [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617 showed a bi-exponential decline in blood concentrations post-dosage, with an initial rapid phase followed by a slower phase. For [68Ga]Ga-PSMA-11, terminal half-life (T1/2; geometric mean) was 3.93 h, total systemic clearance (CL) was 5.52 L/hr, and an apparent volume of distribution (Vz) was 31.3 L. For [177Lu]Lu-PSMA-617, these values were 28.9 h, 1.71 L/hr, and 71.2 L, respectively. For [68Ga]Ga-PSMA-11 dosimetry, kidneys received the largest absorbed doses (0.23 ± 0.14 mGy/MBq), and effective dose was 0.030 mSv/MBq. For a full six-cycle cumulative injected activity of 44.4 GBq of [177Lu]Lu-PSMA-617, the lacrimal glands received the largest estimated absorbed dose of 90 ± 45 Gy. The mean absorbed dose to the kidneys (critical organ) was 0.34 Gy/GBq, resulting in a cumulative absorbed dose of 15 Gy for the full six-cycles. The radiation exposure was evaluated among 13 medical personnel, 8 who participated in administration, and family members. Measurements were taken at 8 sites including patients’ home. External radiation exposure to medical personnel and family members was minimal, with 0 μSv in 6/7 patients and 60 μSv in 1 patient.ConclusionThis is the first prospective Japanese study to demonstrate the use of [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617 in patients with mCRPC. The absorbed doses in various organs for both radiopharmaceuticals were consistent with previously reported data. Minimal radiation exposure observed for medical personnel and caregivers highlights the safety of [177Lu]Lu-PSMA-617 during treatment, ensuring a secure treatment environment.Trial registrationThis study is a prospective, open-label, multicenter, single-arm, phase 2 trial of [177Lu]Lu-PSMA-617 in patients with progressive PSMA + mCRPC in Japan (NCT05114746). The trial was initiated on 25-Jan-2022 (first patient first visit), with a primary analysis data cut-off on 8-Dec-2023. The study is ongoing. A total of 35 patients were screened and received [68Ga]Ga-PSMA-11, of whom 30 were included for efficacy and safety assessments of [177Lu]Lu-PSMA617 across Part 1 (safety run-in), Part 2 (post-taxane), and Part 3 (pre-taxane). Additionally, 3 patients each had evaluable data for PK and dosimetry assessments of [68Ga]Ga-PSMA-11 and [177Lu]Lu-PSMA-617. Informed consent was obtained from all participants before conducting any study-specific procedures.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12149-025-02079-8.

IntroductionDespite the wide range of treatment options available for diabetic macular edema (DME), adherence to treatment remains a barrier. Therefore, this study used conjoint analysis to examine the factors that patients with DME prioritize when choosing a course of treatment and investigated differences in quality of life and levels of disease self-management in patients with or without experience of anti-vascular endothelial growth factor (VEGF) treatment.MethodsA cross-sectional study was conducted through an online survey in Japan between May 31, 2022, and June 30, 2022. Questionnaires were sent to 27,236 individuals registered in the diabetes panels, with experience of treatment for DME within the last 10 years. Conjoint analysis was employed to calculate the relative importance, i.e., degree of influence on patients' treatment choices, considering the trade-offs among five factors: cost per treatment, frequency of visits, anticipated post-treatment visual acuity, physician’s explanation about disease and treatment, and frequency of treatment-related side effects.ResultsA total of 237 responses were used to assess the relative importance of cost per treatment, frequency of visits, anticipated post-treatment visual acuity, physician’s explanation about the disease, treatment, and frequency of treatment-related side effects using conjoint analysis. The importance of each factor was anticipated post-treatment visual acuity at 30.0, frequency of treatment-related side effects at 25.5, treatment frequency at 17.7, cost per treatment at 16.5, and physician explanation about the disease and treatment at 10.4. The average EuroQoL 5 dimension 5 level index value in patients with and without anti-VEGF treatment experience was 0.785 and 0.825, respectively, with no major difference.ConclusionsAnticipated post-treatment visual acuity was identified as the most important factor in selecting a treatment regardless of the anti-vascular endothelial growth factor treatment experience demonstrating when patients with DME make treatment choices, anticipated post-treatment visual acuity is prioritized over treatment frequency and cost.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-024-01026-6.

Psoriatic disease (PsD) is a chronic disease affecting skin (psoriasis) and joints (psoriatic arthritis, PsA) that has a significant impact on patients' quality of life (QOL). We report findings from the Japanese subgroup of patients included in Psoriasis and Beyond: The Global Psoriatic Disease Survey, a cross-sectional, quantitative online survey of patients with self-reported, healthcare professional (HCP)-diagnosed, moderate-to-severe plaque psoriasis, with or without PsA. Eligible patients who were recruited online completed a 25-min internet-based survey in Japanese. We assessed patients' understanding of the systemic nature of PsD, disease burden, perception towards their HCPs, treatment expectations, and satisfaction with care. Of the 148 patients, 74% were females. In total, 65% of patients were aware of the systemic nature of their disease. A minority of patients (27%) were aware that PsA was related to their psoriasis, and 30% and 42% of patients were unaware of any manifestations and comorbidities, respectively, related to PsD. Overall, 21% of patients reported that their disease has a "very large" to "extremely large" impact on their QOL (assessed by Dermatology Life Quality Index score), while the majority (61%) reported a "small" effect or "no effect" at all on QOL. Patients experienced stigma and discrimination and had a negative impact on relationships due to PsD. More patients with psoriasis and concomitant PsA (66%) were satisfied with their current treatment than those with psoriasis alone (46%). Overall, 41% of patients were not involved in deciding their treatment goals. These results suggest that Japanese patients may not be fully aware of the systemic nature of PsD, its manifestations and comorbidities. While these patients were somewhat satisfied with their current treatment, they were only occasionally consulted in deciding treatment goals. Policy measures are required to address the stigma and discrimination experienced by patients. Increased patient participation in their care supports shared decision-making and enhanced treatment outcomes.

Asciminib is a first-in-class BCR::ABL1 inhibitor that Specifically Targets the ABL1 Myristoyl Pocket (STAMP). It is approved worldwide and in Japan for chronic myeloid leukemia in chronic phase (CML-CP) with resistance or intolerance to previous tyrosine kinase inhibitor (TKI) therapy. In the Phase 3 ASCEMBL study, patients with CML-CP who received ≥ 2 prior ATP-competitive TKIs were randomized (2:1) to asciminib 40 mg twice-daily or bosutinib 500 mg once-daily. Here, we report the 96-week results of the subgroup analysis of Japanese patients (asciminib, n = 13; bosutinib, n = 3) in the ASCEMBL study. The MMR rate at Week 96 was 46.2% in asciminib-treated patients, increasing from Weeks 24 and 48. Patients who achieved MMR at Week 24 remained in MMR up to the Week 96 cutoff. While a high proportion of patients treated with asciminib remained on treatment at cutoff, none randomized to bosutinib were on treatment at Week 96. Despite the longer duration of exposure to asciminib, its safety and tolerability continued to be favorable with no new or worsening safety findings. Overall, the efficacy and safety outcomes in the Japanese subgroup were comparable with the ASCEMBL global study population, which supports the use of asciminib in Japanese patients with previously treated CML-CP.

Lower systolic blood pressure (SBP) is known to be associated with poor prognosis in heart failure (HF). We evaluated the efficacy and safety of sacubitril/valsartan according to baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. In all, 223 patients were stratified into tertiles according to baseline SBP (≤114 mmHg: n=75; >114 and ≤130 mmHg: n=76; and >130 mmHg: n=72). Patients with lower SBP (≤114 mmHg) had the highest median N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations at baseline (P=0.0184). No significant difference was observed between sacubitril/valsartan and enalapril for the composite outcome of cardiovascular death and HF hospitalization across SBP tertiles (P-interaction=0.2682). Although the P-interaction value was not significant (0.2106), a greater reduction in NT-proBNP with sacubitril/valsartan compared with enalapril was observed in patients with SBP >130 mmHg (P=0.0076). The incidence of hypotension-related events and reduction or discontinuation of treatment due to hypotension-related events was higher in the lower SBP subgroup, and these events were more frequent in the sacubitril/valsartan than enalapril group. The efficacy of sacubitril/valsartan compared with enalapril was consistent across baseline SBP tertiles in Japanese patients from the PARALLEL-HF study. Hypotension-related events were more common in patients treated with sacubitril/valsartan with lower SBP.

The PARALLEL-HF study assessed the efficacy and safety of sacubitril/valsartan vs. enalapril in Japanese patients with chronic heart failure with reduced ejection fraction (HFrEF). This open-label extension (OLE) assessed long-term safety with sacubitril/valsartan. This study enrolled 150 patients who received sacubitril/valsartan 50 or 100 mg, b.i.d., in addition to optimal background heart failure (HF) therapy. A dose level of sacubitril/valsartan 200 mg, b.i.d., was targeted by Week 8. At OLE baseline, higher concentrations of B-type natriuretic peptide (BNP) and urine cGMP, and lower concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP), were observed in the sacubitril/valsartan core group (patients who received sacubitril/valsartan in both the core and extension study) than in the enalapril core group (patients who received enalapril in the core study and were then transitioned to sacubitril/valsartan). The mean exposure to study drug was 98.9%. There was no trend of worsening of HF at Month 12. No obvious changes in cardiac biomarkers were observed, whereas BNP and urine cGMP increased and NT-proBNP decreased in the enalapril core group, which was evident at Weeks 2-4 and sustained to Month 12. Long-term sacubitril/valsartan at doses up to 200 mg, b.i.d., has a positive risk-benefit profile; it was safe and well tolerated in Japanese patients with chronic HFrEF.