Daiichi Sankyo (United Kingdom)

We have developed the methylotrophic yeast Ogataea minuta as a useful host for producing heterologous proteins. In this study, a double mutant that lacks the Prb1 protease and alcohol oxidase was generated and applied for heterologous protein production. Upon our optimization of the fermentation conditions, such as feeding of carbon and nitrogen sources and pH control, this mutant showed increased production of human serum albumin, resulting in a yield of approximately 7.5 g/L at 21 days in the production phase. The established optimal fermentation condition with the double mutant was successfully applied to manufacture a candidate biologic protein: lipocalin derivative which is designed to attach to the calcitonin gene-related peptide, on an industrial scale. The candidate biologic protein was successfully manufactured at an industrial scale in a 4500 L bioreactor under well-controlled conditions. This first successful case highlights the potential of our O. minuta-based production system, and this study is helpful for a large-scale cultivation of a methylotrophic yeast for protein production.

Atrial fibrillation (AF) after bioprosthetic valve (BPV) replacement is common in older patients with multiple comorbidities and is associated with a heightened risk of thromboembolism. Anticoagulation therapy is often indicated, but renal impairment and other comorbidities elevate bleeding risk, making clinical decisions complex. This study compared clinical outcomes between warfarin and direct oral anticoagulants (DOACs) in this high-risk population. This subgroup analysis of the BPV-AF Registry included 612 patients treated with oral anticoagulants after BPV replacement, stratified by renal function: normal or mild impairment (creatinine clearance [CCr] ≥50 mL/min), mild-to-moderate impairment (30 mL/min ≤ CCr < 50 mL/min), and moderate-to-severe impairment (15 mL/min ≤ CCr < 30 mL/min). Baseline characteristics and outcomes were analyzed within each stratum. The composite outcome of stroke, systemic embolism, and cardiovascular events was numerically less frequent in the DOAC than warfarin group across all strata, although the differences were not statistically significant. Major bleeding also tended to be lower in the DOAC group. In this study from a Japanese nationwide registry comparing outcomes of AF patients after BPV replacement with severe renal impairment between those treated with DOACs and those treated with warfarin, comparative conclusions between DOACs and warfarin cannot be drawn because of the small sample size. Nonetheless, both anticoagulants may be acceptable in clinical practice, highlighting the need for individualized decision-making based on patient risk.

Abstract Background In the breast cancer treatment, there may be a gap between patients’ information needs and physicians’ perceptions. To address this issue, we conducted a comprehensive questionnaire survey aimed to assess the specific information needs of patients regarding the adverse events (AEs) associated with treatment. Methods A web-based questionnaire survey (UMIN000049280: Registered on October 31, 2022) was conducted in patients with a history of breast cancer treatment. Responses were obtained regarding AEs experienced, AEs for which remedies were identified, AEs patients sought to prevent, and pre-treatment information on AEs patients desired to have. Results Data from 435 breast cancer patients were analyzed. The most common AEs reported included hair loss (93.3%), malaise/fatigue (89.4%), nail changes (83.2%), dysgeusia (69.0%), leukopenia/white blood cell decreased (65.1%), neuropathy (62.3%), and nausea/vomiting (61.4%). Financial anxiety was reported in 35.2% of the participants. AEs for which a minority of patients found effective solutions included neuropathy (20.3%), financial anxiety (21.6%), edema (24.3%), joint pain (26.0%), and malaise/fatigue (26.7%). Patients expressed the greatest desire to avoid hair loss (34.7%), followed by nausea/vomiting (23.7%), interstitial lung disease/pneumonitis (5.5%), malaise/fatigue (5.1%), and dysgeusia (5.1%). The most commonly requested pre-treatment information regarding AEs was their duration, followed by prevention methods, management strategies, time to onset, and the impact on daily life. Conclusions This survey highlights the existence of significant unmet medical needs among breast cancer patients, due to the inadequate solutions available for managing AEs associated with various therapeutic agents. In addition, the survey revealed that patients have different information needs regarding different types of AEs.