A scoping review of frameworks evaluating digital health applications.

Objectives: Despite rapid technological advances, the adoption and deployment of digital health and virtual reality (VR) applications in healthcare appears to be progressing slowly. This scoping review is part of the Scale-Up4Rehab (SU4R) project, which aims to create a virtual rehabilitation clinic hosting high-quality digital health interventions. The aim of this review was to identify existing high-quality digital health evaluation frameworks, and from these, extract criteria to inform a new set of guidelines for assessing the applications that will be hosted on the SU4R platform.

First-in-human study of an EGFRvIII x CD3 T cell bispecific antibody in the treatment of newly diagnosed glioblastoma.

Background: This first-in-human study evaluated EGFRvIII × CD3 TCB, a novel T cell bispecific antibody, in patients with newly diagnosed EGFRvIII-positive glioblastoma.

Methods: Patients with newly diagnosed glioblastoma received escalating doses of EGFRvIII × CD3 TCB following chemoradiation. The primary objectives were to evaluate safety/tolerability and define the maximum tolerated dose (MTD); secondary objectives included pharmacokinetics (PK), immunogenicity, pharmacodynamics, and clinical activity.

A Phase 3 Study of the Efficacy and Safety of Pexidartinib in East Asian Patients with Tenosynovial Giant Cell Tumor.

Introduction: The aim of this study was to assess the efficacy and safety of pexidartinib, an inhibitor of colony-stimulating factor 1 receptor, in East Asian patients with tenosynovial giant cell tumor (TGCT).

Methods: This multicenter, single-arm, phase 3 study (NCT04488822) enrolled patients with symptomatic TGCT to receive pexidartinib 400 mg twice daily. The primary efficacy endpoint was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.

Safety and Immunogenicity of a Pneumococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric Vaccines in Healthy Toddlers and Infants.

Background: A 21-valent pneumococcal conjugate vaccine, PCV21, was developed to provide broader coverage against Streptococcus pneumoniae serotypes. PCV21 comprises 13 serotypes common to a licensed 13-valent pneumococcal conjugate vaccine (PCV13) and 8 additional serotypes. This study evaluated 3 PCV21 formulations with differences in antigen content for some serotypes, compared with PCV13, administered concomitantly with routine pediatric vaccines.

Clinical Validity of FoundationOne Liquid CDx for Detection of BRAFV600E in Colorectal Cancer.

Purpose: The BRAF inhibitor encorafenib (Enco) plus the anti-EGFR antibody cetuximab (Cetux) improved overall survival, objective response rate, and progression-free survival in previously treated BRAFV600E-mutant metastatic colorectal cancer in BEACON, a phase III randomized trial, leading to regulatory approval for this indication. To support rapid, plasma-based testing for BRAFV600E identification, clinical validity of a ctDNA-based assay, FoundationOneLiquid CDx (F1LCDx), was assessed against the reference tumor-based clinical trial assay (CTA) in liquid biopsy-evaluable samples from BEACON and commercially obtained tissue-matched plasma samples.

Patients And Methods: Pretreatment tissue samples were collected in BEACON to confirm BRAF mutational status using the central single gene PCR assay.

Significance of Pulmonary Vascular Dysfunction in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is frequently accompanied by abnormalities of the pulmonary vasculature. This vasculopathy spans the spectrum from mild vascular dysfunction to pulmonary hypertension, which on rare occasions can be severe. Given the worldwide prevalence of COPD, it is conceivable that the morbidity and mortality associated with pulmonary vascular dysfunction have been vastly underappreciated, especially in countries and regions where the infrastructure and resources to define the magnitude of the problem are often limited.

Safety of budesonide/glycopyrronium/formoterol fumarate dihydrate delivered by HFO-1234ze versus HFA-134a in chronic obstructive pulmonary disease: a phase 3, multi-site, randomised, double-blind, parallel-group, active-comparator study.

Background: Pressurised metered dose inhalers (pMDIs) contain a hydrofluorocarbon propellant, such as hydrofluoroalkane-134a (HFA-134a), which is known to have global warming potential (GWP). Transitioning pMDIs to propellants with lower GWP will reduce the environmental impact of pMDIs. This study assessed the safety of a near-zero GWP propellant, hydrofluoroolefin-1234ze (HFO-1234ze), compared with HFA-134a when used in the delivery of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) in participants with chronic obstructive pulmonary disease (COPD).

Population Exposure-Response Efficacy Analysis of Elranatamab (PF-06863135) in Patients with Multiple Myeloma.

Background: Elranatamab is a heterodimeric humanized full-length bispecific antibody composed of one B-cell maturation antigen (BCMA) binding arm and one cluster of differentiation 3 (CD3) binding arm. Results from the MagnetisMM-3 study indicated deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM).

Objective: The current analysis was conducted to characterize the relationship between free (i.

A randomized study of apalutamide in Chinese patients with non-metastatic castration-resistant prostate cancer.

This post-approval commitment study addressed the limited data on the safety and efficacy of apalutamide in Chinese patients with non-metastatic castration-resistant prostate cancer (NM-CRPC). Utilizing a double-blinded, placebo-controlled trial with pre-planned crossover design, 75 patients were randomized (2:1) to receive apalutamide 240 mg daily or placebo while continuing androgen deprivation therapy. Apalutamide significantly reduced the risk of prostate-specific antigen (PSA) progression by 76.

Recent Utilization of Pediatric Extrapolation and Modeling and Simulation Approaches in Pediatric Drug Development in Japan.

In Japan, the percentage of approved drugs with pediatric indications increased to 30% in 2010-2015, but no further increase was observed through 2020. The Ministry of Health, Labor, and Welfare in Japan presented draft future directions to promote pediatric drug development, where the modeling and simulation (M&S) approach was introduced as a tool to support efficacy and safety, utilizing existing data when building a flexible data package for pediatric drug approval. M&S is considered a powerful scientific tool in pediatric drug development using the pediatric extrapolation approach.

Tasurgratinib (E7090) for cholangiocarcinoma with fibroblast growth factor receptor 2 fusions/rearrangements: a multicenter, open-label, Phase 2 study.

Background: This Phase 2 study (NCT04238715) evaluated the efficacy/safety of tasurgratinib 140 mg daily in patients with cholangiocarcinoma (CCA) and fibroblast growth factor receptor (FGFR) 2 fusions/rearrangements.

Methods: Eligible Japanese and Chinese patients who had surgically unresectable, advanced, or metastatic CCA and had received ≥1 prior gemcitabine-based combination chemotherapy regimen were included and treated with oral tasurgratinib 140 mg daily. The primary endpoint was objective response rate (ORR); the study was considered successful if the lower limit of the ORRs 90% CI was >15%.

Comparative Morphometric and Histometric Evaluation of Power-Dependent Tissue Ablation Using Fractional Carbon Dioxide Laser.

Background: Fractional carbon dioxide (CO) lasers are commonly used in dermatological resurfacing, offering precise ablation and controlled dermal remodeling. Although clinical outcomes vary with the energy and pulse settings, comparative morphometric and histometric data on power-dependent tissue interactions are limited.

Objective: To evaluate and compare fractional CO laser-induced microscopic thermal zones (MTZs) ablation characteristics at peak powers of 30 W and 40 W using an ex vivo porcine skin model.

Immediate-use rescue medication and the epilepsy monitoring unit: experiences from an expert panel.

Background: People with epilepsy (PWE) may experience seizure clusters, broadly defined as ≥2 seizures that occur in close proximity. In epilepsy monitoring units (EMUs), seizure clusters can spontaneously occur during long-term videoelectroencephalogram monitoring (LTVEM) or as a result of antiseizure medication dose adjustments. In this survey, we examined the experiences and practices of expert clinicians with seizure clusters in EMUs.

Low Lung Function in Middle-Aged Smokers Impacts Health Status, Morbidities, and Mortality: An Observational Analysis of the Lovelace Smokers Cohort.

Background: Pulmonary function tests may predict future outcomes; however, they are not often performed in middle aged individuals at risk for future airway obstruction. We examined whether smokers with low lung function have increased risk of developing health problems and mortality over time.

Methods: Current and ever smokers (n=830) from the Lovelace Cohort aged 40-60 years without baseline airway obstruction and with at least two spirometry measurements over 18 months were included.

Efficacy and Safety of IncobotulinumtoxinA for Treatment of Sialorrhea: A Multicenter, Phase 3 Study in Japan.

Background: Sialorrhea, caused by various neurological diseases, impairs patient health and quality of life. After the results of a randomized controlled trial, incobotulinumtoxinA was approved for the treatment of chronic sialorrhea in the United States and Europe; however, no pharmacotherapy has been approved in Japan.

Objective: The aim was to evaluate the efficacy and safety of incobotulinumtoxinA treatment for chronic sialorrhea in a single-arm phase 3 study in Japan.

Pooled analysis of trastuzumab deruxtecan retreatment after recovery from grade 1 interstitial lung disease/pneumonitis.

Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate treatment for multiple solid tumors, carries risk of interstitial lung disease/pneumonitis (ILD). Management guidelines generally mandate interrupting T-DXd treatment for grade 1 ILD, with possible retreatment following resolution of imaging findings. This pooled analysis examined T-DXd retreatment duration and ILD recurrence following recovery from grade 1 ILD.

The Effect of Liv.52 DS in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD): A Pilot, Randomized, Double-Blind, Placebo-Controlled, Clinical Study.

Purpose: Metabolic dysfunction-associated fatty liver disease (MAFLD) is considered a major global health concern. Considering the preliminary trend of hepatoprotective function of Liv.52 DS, the present study was conducted to explore its role in MAFLD.

Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival in Oncology Clinical Trials.

Time-to-event endpoints, such as progression free survival (PFS) and overall survival (OS), are critical in assessing therapeutic efficacy in oncology drug development. However, their quality and interpretability are frequently challenged by a range of factors, from protocol design and intercurrent events (ICE) to inconsistent data collection and missing follow-up data. These methodological and operational complexities can obscure the true treatment effect.

Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia-specific perspectives.

The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease-modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment-induced changes in disease biology. These frameworks enable opportunities for personalized interventions-encompassing pharmacological and non-pharmacological strategies-and for enhanced clinical trial design.

Deciphering differential biomarkers for anti-interleukin-6 receptor and anti-tumour necrosis factor-α treatment response in rheumatoid arthritis by multiomics analysis.

Objective: To identify blood-based predictive and pharmacodynamic biomarkers at different timepoints in patients with active rheumatoid arthritis (RA) treated with anti-interleukin-6 receptor (anti-IL-6R) and anti-tumour necrosis factor-α (anti-TNF-α).

Methods: This study used blood samples from the MONARCH trial (NCT02332590), a randomised, double-blind, phase III trial that compared the safety and efficacy of sarilumab (anti-IL-6R) and adalimumab (anti-TNF-α) monotherapy in patients with RA who were intolerant/inadequate responders to methotrexate. The study evaluated predictive biomarkers to anti-IL-6R and anti-TNF-α treatments at baseline and week 2 and pharmacodynamic biomarkers at week 2 and week 24 using Olink proteomics analysis (n=804 serum samples from 268 patients).

The effects of lacosamide, pregabalin, and tapentadol on peripheral nerve excitability: A randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects.

Background: Chronic pain is a leading cause of disability globally, with limited treatment options and frequent adverse effects. The IMI-PainCare-BioPain project aimed to enhance analgesic drug development by standardizing biomarkers. This study, IMI2-PainCare-BioPain-RCT1, evaluated the effects of lacosamide, pregabalin, and tapentadol on peripheral nerve excitability in healthy subjects through a randomized, double-blind, placebo-controlled crossover trial.

Long-term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes and chronic kidney disease: A 52-week postmarketing clinical study (TWINKLE).

Aim: To evaluate the long-term safety and efficacy of imeglimin in Japanese individuals with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD).

Materials And Methods: This open-label, single-arm, multicenter, phase 4 study (TWINKLE) enrolled individuals with T2D and estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m, treated with ≤1 oral hypoglycemic agent.

Metabolism of new drug modalities research advances - 2024 year in review.

New drug modalities (NDMs) have gained significant popularity and attention in recent years due to their ability to target previously undruggable pathways and offer new strategies for tackling complex diseases. This trend is reflected in our review, which encompasses 17 publications, an increase from 11 last year and includes a growing number of contributors across industry and academia. We have focused on five categories of NDMs: (1) Peptides with an emphasis on macrocyclic structures; (2) Bivalent protein degraders, also known as proteolysis-targeting chimeras (PROTACs); (3) Conjugated drugs, including peptide-drug and antibody-drug conjugates; (4) Antisense oligonucleotides and -acetylgalactosamine (GalNAc) conjugated oligonucleotides; and (5) Covalent inhibitors.