GlaxoSmithKline (Japan)

In ASPEN (<ext-link>NCT04594369</ext-link>), brensocatib 10 and 25mg significantly reduced the annualized rate of adjudicated pulmonary exacerbations (PEx) over 52 weeks (wks; primary endpoint) vs placebo (pbo) in patients (pts) with non-cystic fibrosis bronchiectasis (hereafter bronchiectasis); brensocatib 25mg significantly reduced the decline in post-bronchodilator FEV₁. Here we report efficacy and safety for Japanese pts. Pts with bronchiectasis who had PEx in the 12 months before screening (adults [18-85 yr], ≥2; adolescents [12-<18 yr], ≥1) were randomized to once-daily brensocatib (10 or 25mg) or pbo for 52 wks. Endpoints included annualized PEx rate, time to first PEx, PEx-free, and change from baseline in FEV₁, Quality of Life-Bronchiectasis Respiratory Symptoms Domain score (QOL-B RSS), and FVC. Baseline characteristics for Japanese pts (n=87) were generally consistent across treatment arms; pts in the brensocatib 25mg arm had higher post-bronchodilator FEV₁ (Table). Brensocatib 10 and 25mg reduced annualized PEx rate, prolonged time to first PEx, and increased pts remaining PEx-free vs pbo. Brensocatib 10 and 25mg reduced FEV₁ and FVC decline, and improved QOL-B RSS vs pbo. Adverse events were similar across groups. Consistent with the overall trial, brensocatib showed benefit across all endpoints including PEx, lung function, and QOL-B RSS vs pbo in Japanese pts, with a numerically higher effect. <fig><object-id>erj;66/suppl_69/PA4947/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

ABSTRACTNucleos(t)ide analogue (NA) therapy is the current standard of care for chronic hepatitis B (CHB) virus infection but rarely achieves functional cure, necessitating long‐term therapy, which often leads to nonadherence and increased treatment burden. This retrospective cohort study was designed to describe treatment discontinuation and adherence to second‐generation NAs among patients with CHB in Japan. We used the Japanese Medical Data Center Claims Database (JMDC Inc.) to identify adults with CHB who were newly initiated on a single‐agent, second‐generation NA between January 2007 and August 2023. Outcomes included treatment discontinuation and adherence, treatment restart after discontinuation, NA switching and factors associated with treatment discontinuation/adherence. Of the 2473 patients included in this study (mean age 49.9 years), 65.6% were male. The most common index NAs were entecavir (55.5%) and tenofovir alafenamide fumarate (TAF, 36.2%). Treatment discontinuation was observed in 20.3% of patients; mean time to discontinuation was 20.4 months. Of the patients who discontinued, 50.7% restarted NAs. Mean adherence (proportion of days covered [PDC]) was 0.87, and 81.2% of participants had PDC ≥ 80%. Age group 35–64 years, index treatment TAF and baseline hepatocellular carcinoma diagnosis were significantly associated with a decreased probability of treatment discontinuation and nonadherence. Although a high proportion of patients were persistent and adherent to NA treatment, there is a subgroup of patients whose needs are not met while receiving NA treatment, particularly in younger age groups. The results emphasise the need for alternative therapies with shorter, finite treatment durations to improve patient persistence, adherence and outcomes.

IntroductionLupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase.Methods and analysisThis multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab’s effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations.Ethics and disseminationThis study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings.

Evaluate long-term safety, tolerability, and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE Responder Index (SRI)-4 response rate, SRI-4 components, severe SLE flare, and use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first belimumab dose received in either parent or current study through to study end. Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index responders. The proportion of patients with no worsening in PGA (91.2-100.0%) and no new organ damage (92.6-100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. Favourable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

<b>Background:</b> In patients with uncontrolled asthma despite ICS/LABA, effects of adding LAMA or increasing ICS may vary by FEV₁ reversibility. <b>Aim:</b> Investigate whether reversibility at screening predicts response to adding UMEC or increasing FF dose. <b>Methods:</b> CAPTAIN: Phase IIIA, randomised, double-blind, 24–52-week, parallel-group study in adults with uncontrolled asthma and airflow reversibility at screening (≥12% and ≥200mL). Treatment: FF/VI (100/25, 200/25μg) or FF/UMEC/VI (100/31.25/25, 100/62.5/25, 200/31.25/25, 200/62.5/25μg) QD (ELLIPTA). Outcomes: change from baseline in trough FEV₁ (Wk 24), annualised moderate/severe exacerbation rate (Wks 1–52), by reversibility at screening (post hoc analyses). <b>Results:</b> Numerically greater improvements in trough FEV₁ were seen with adding UMEC or increasing FF across the range of reversibility (<b>Fig 1</b>). Increasing FF led to greater numerical reductions in exacerbation rate across the range of reversibility; adding UMEC had minimal impact (<b>Fig 2</b>). <b>Conclusions:</b> Effects of adding UMEC or increasing FF were largely independent of FEV₁ reversibility at screening. <b>Funding:</b> GSK (205715/NCT02924688)

Daprodustat is a hypoxia‐inducible factor‐prolyl hydroxylase inhibitor for the treatment of anemia of chronic kidney disease. This phase 3 study evaluated the efficacy and safety of daprodustat in an uncontrolled cohort of 56 Japanese peritoneal dialysis patients with anemia over 52 weeks. Subjects received daprodustat 4 mg orally once daily for 4 weeks and the dose was subsequently adjusted every 4 weeks. Mean baseline hemoglobin was 10.9 g/dL (95% CI 10.59, 11.12). Mean hemoglobin reached the target range (11.0–13.0 g/dL) at week 12 and was maintained until week 52. Mean hemoglobin during weeks 40–52 was 12.1 g/dL (95% CI 12.0, 12.2). The most frequent adverse events included nasopharyngitis (29%), catheter‐site infection (18%), peritonitis (16%), diarrhea (14%), and nausea (11%). No deaths were reported. Once‐daily oral daprodustat treatment was generally well tolerated and mean hemoglobin was achieved and maintained within the target range in Japanese peritoneal dialysis participants.

The current success rate of a drug candidate, from the beginning of the clinical trial to receiving marketing approval, is about 10%–20%, and it has not changed during the past few decades. Therefore, pharmaceutical companies are under pressure to select one compound, among many others, with a high probability of success. The differences in drug features affect their probabilities of approval success. In this study, we examined the approval success rates of drug candidates, developed in the United States, the European Union, or Japan, by focusing on four parameters (“drug target,” “drug action,” “drug modality,” and “drug application”) and their combinations, and identified factors that conditioned the outcome of the drug development process. We obtained a total success rate of 12.8%, after evaluating 3999 compounds. Moreover, after analyzing the combinations of these parameters, the approval success rates of drugs that corresponded to the following categories—a stimulant in drug action or an enzyme in drug target and biologics (excluding monoclonal antibody) in drug modality—were high (34.1% and 31.3%, respectively). Univariate and multivariate logistic regression analyses revealed that stimulant in drug action, and “B” (blood and blood forming organs), “G” (genito‐urinary system and sex), and “J” (anti‐infectives for systemic use) in drug application were statistically associated with high approval success rates. We found several parameters and their combinations that affected drug approval success rates. Our results could assist pharmaceutical companies in evaluating the probability of success of their drug candidates and, thus, in efficiently conducting the clinical development process.