The Takeda Pharmaceutical Company Limited (武田薬品工業株式会社, Takeda Yakuhin Kōgyō kabushiki gaisha) [takeꜜda jakɯçiŋ koꜜːɡʲoː] is a Japanese multinational pharmaceutical and biopharmaceutical company. It is the largest pharmaceutical company in Asia and one of the top 20 largest pharmaceutical companies in the world by revenue (top 10 following merger with Shire). The company has over 49,578 employees worldwide and achieved US$19.299 billion in revenue during the 2018 fiscal year. The company is focused on metabolic disorders, gastroenterology, neurology, inflammation, as well as oncology through its independent subsidiary, Takeda Oncology. Its headquarters is located in Chuo-ku, Osaka, and it has an office in Nihonbashi, Chuo, Tokyo. In January 2012, Fortune Magazine ranked the Takeda Oncology Company as one of the 100 best companies to work for in the United States.
This post-marketing surveillance study assessed the safety and effectiveness of guanfacine hydrochloride extended-release (GXR) in adults with attention-deficit/hyperactivity disorder (ADHD) in routine clinical practice in Japan. In this prospective, multicenter study, adults (≥ 18 years) were followed for 1 year after initiating GXR treatment or until treatment discontinuation, whichever occurred first (enrollment: June 2020–March 2022). Hypotension and bradycardia, syncope, blood pressure elevation upon discontinuation, and QT prolongation were key safety concerns for evaluation. Missing data were not imputed; therefore, effectiveness outcomes reflect only the observed data. In total, 961 patients were enrolled across 155 sites; case report forms were collected for 949 patients. Of these, 912 and 784 were included in the safety and effectiveness analyses, respectively. The 12-month GXR continuation rate was 45.2
The number of clinical investigations and approved applications of adeno-associated virus (AAV) based transgene product (TP) delivery has grown steadily. There also has been a growing interest in understanding how anti-AAV and anti-TP immune responses affect the safety and efficacy of these gene therapy treatments. While considerations related to anti-AAV immunity have been discussed in other works, this manuscript focuses on the assessment of anti-TP immune responses, including both humoral and cellular responses. The development of anti-TP antibodies or a cytotoxic cellular response may lead to increased clearance of the TP, elimination of AAV-transduced cells, and consequently, affect the overall durability and efficacy of the treatment. Additionally, the binding and neutralization of residual endogenous protein by anti-TP antibodies might further worsen the clinical condition under treatment. Several topics are explored in this manuscript, including immunogenicity risk factors that can be considered when evaluating the overall risk and impact of anti-TP immunogenicity, potential implications of anti-TP immunogenicity, the importance of assessing anti-TP immunogenicity, and the commonly used analytical methodologies. The manuscript proposes an approach to determining the scope of anti-TP immunogenicity assessment for clinical and non-clinical studies, based on the TP nature, other intrinsic and extrinsic risk factors. Authored by a group of scientists involved in AAV-based therapeutic development from various industry organizations, the manuscript aims to provide recommendations and guidance to industry sponsors, academic laboratories, and regulatory agencies working on AAV-based modalities, with the goal of achieving a more consistent approach to the assessment of anti-TP immune response.
Introduction The optimal treatment target for Crohn’s disease (CD) is unknown. Targeting transmural healing (TMH) may be associated with a lower risk of complications than clinical and endoscopic outcomes. The Study to Evaluate Transmural Healing as a Treatment Target in Crohn’s Disease (VECTORS) aims to investigate TMH as a potential treatment target and its long-term benefits in patients with CD.Methods and analysis VECTORS is a phase 4, interventional, parallel-group, multicentre, randomised controlled trial. Approximately 304 adult patients with moderately to severely active CD from multiple international sites will be enrolled and randomly assigned in a 1:1 ratio to treatment target group 1 (corticosteroid-free intestinal ultrasound-based response or TMH plus clinical and biomarker remission) or group 2 (corticosteroid-free clinical and biomarker remission). All patients receive vedolizumab according to the standard dosing regimen, with an additional dose at week 10, followed by a treatment escalation algorithm to reach the assigned targets. Randomisation will be stratified by prior advanced therapy exposure, disease location and disease duration. The primary objective is to determine if treatment target group 1 is superior to group 2 for the primary efficacy outcome of corticosteroid-free endoscopic remission at week 48. CD-related complications (key secondary outcome) are assessed at week 96.Ethics and dissemination The trial is conducted in compliance with the protocol and applicable regulatory requirements and is approved by institutional review boards/independent ethics committees at the country or site level. Patients’ written informed consents are obtained and documented prior to trial participation. Findings will be disseminated in peer-reviewed journals and at scientific congresses.Trial registration numbers NCT06257706; EUCT, 2023-509096-16-00.
Accurate assessment of tissue distribution for oligonucleotide therapeutic (ONT) drug candidates is essential for understanding pharmacokinetic behavior and predicting therapeutic efficacy. ONTs present a unique challenge with their rapid systemic clearance coupled with prolonged tissue retention, making comprehensive tissue concentration evaluation critical for successful drug development. The IQ Consortium Tissue Concentration Working Group surveyed member companies about their current tissue concentration assessment methods to understand industry practices and identify areas for improvement. Most companies reported that ONTs still represent a relatively small portion of their pre-candidate selection portfolios, reflecting the evolving nature of this therapeutic modality. siRNAs dominated development efforts across surveyed organizations, followed by antisense oligonucleotides, indicating clear therapeutic class preferences within the industry. Assessment strategies varied considerably across organizations, highlighting different approaches to resource allocation and risk management. While some companies routinely evaluate tissue concentrations for all ONT programs regardless of indication or target, others take a more selective, program-dependent approach based on compound characteristics and therapeutic objectives. Despite this strategic variability, there was universal reliance on LC-MS for quantification, often supplemented with qPCR/RT-qPCR and hybridization assays for comprehensive analytical coverage. All surveyed companies integrate tissue concentration data into translational pharmacokinetic modeling efforts, yet few have adopted physiologically-based pharmacokinetic (PBPK) models as standard practice. Companies recognize the value of improving ONT tissue distribution assessment through standardized methodology tailored to specific oligonucleotide classes.
BACKGROUND:CD8 T cells mediate the effects of cancer immunotherapies. CD8 positron emission tomography (PET) imaging with [89Zr]Zr-berdoxam-crefmirlimab enables whole body CD8 cell assessment and has been shown to be safe in Phase I evaluation. The correlation between CD8 PET imaging parameters and the quantity of CD8 cells assessed by the gold standard of immunohistochemistry (IHC) is unknown. METHODS:The Phase II, prospective multicenter study (iCorrelate) tested the correlation between CD8 PET and CD8 cells by IHC of core needle biopsies from patients with solid tumors receiving immune checkpoint blockade. The safety of repeat CD8 PET was additionally analyzed. RESULTS:49 patients had 70 biopsies (37 baseline and 33 on-treatment) for correlating CD8 PET with IHC. Standard uptake value mean of the biopsied tumor normalized to aorta showed a correlation with IHC of 0.49 (95% CI 0.26 to 0.59). The correlation was 0.71 (95% CI 0.48 to 0.85) in patients with renal cell carcinoma. Repeat CD8 PET imaging on-treatment was safe. CONCLUSIONS:We found a modest correlation between CD8 PET with [89Zr]Zr-berdoxam-crefmirlimab and intratumoral CD8 cell counts, likely because core needle biopsies do not fully represent the intratumoral heterogeneity of the CD8 cell distribution. Continued research is essential to evaluate in vivo CD8 PET signals, autoradiography, and CD8 T-cell presence by IHC in fully resected tumors. Further studies investigating the correlation between CD8 PET and immunotherapy outcomes are necessary to determine whether CD8 PET imaging could become a valuable tool for guiding immunotherapy development and informing clinical decision-making.
