Nippon Kayaku (Japan)

IntroductionCT-P6, the first trastuzumab biosimilar, was approved on the basis of data limited to human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Usage for other indications was granted by extrapolation, and post-approval clinical studies were conducted to confirm the effect of CT-P6 in HER2-positive gastric cancer.MethodsAfter approval in Japan in 2018, a prospective post-marketing surveillance was conducted in 171 patients (130 male, 41 female) with HER2-positive unresectable advanced or recurrent gastric cancer. The safety and efficacy of CT-P6 were evaluated over 1 year.ResultsCT-P6 was primarily combined with fluoropyrimidine and/or platinum agents. Adverse events occurred in 151 patients (88.3%), with 55 patients (32.2%) experiencing grade 3 or higher. Infusion reactions occurred in 12.3%. Four cardiac disorders were reported: two of grade 1 cardiac dysfunction and two of severe ischemic heart disease. Interstitial lung disease was reported in four patients (2.3%). The objective response rate was 34.4%, and the disease control rate was 82.4%. The progression-free survival (PFS) was 7.4 months. Significant risk factors for PFS included gastroesophageal junction, ≥ 3 metastases, no gastrectomy, prior chemotherapy, and no platinum agent.ConclusionsIn this cohort study, CT-P6 demonstrated sufficient efficacy and no new safety concerns in HER2-positive advanced gastric cancer, serving as a cost-effective alternative to originator trastuzumab.Trial RegistrationJapan Registry of Clinical Trials, Trial ID: jRCT2071230094 (November 2023)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-025-00341-7.

Based on extrapolation of similar clinical outcomes in rheumatoid arthritis to the originator infliximab (IFX) in randomized clinical trials, the first biosimilar antibody CT‐P13 was approved for the treatment of psoriasis. To evaluate the safety, efficacy, and drug survival of CT‐P13 for psoriasis in real‐world clinical practice, prospective post‐marketing surveillance was conducted in 165 Japanese psoriasis patients. During a 1‐year follow‐up period, adverse drug reactions (ADRs) occurred in 29 patients (17.6%). Infusion reaction was the most frequent ADR (6.7%), and mild pneumonia was reported as the only case of infection. Serious ADRs were reported in two patients (1.2%): acute cholecystitis and interstitial pneumonia. The interstitial pneumonia developed after a single infusion of CT‐P13 and the patient died of respiratory failure. In naive patients to biologic therapy (n = 44), the Psoriasis Area Severity Index (PASI) decreased rapidly after the start of CT‐P13 treatment, and response rate achieving an absolute PASI score <1 was 55% at 30 weeks. The response rate was high (78%) in patients with psoriatic arthritis, and 40% and 20% in those in plaque psoriasis and pustular psoriasis, respectively. Of patients switched from IFX to CT‐P13 mainly for nonmedical reasons (n = 105), 57% had already reached PASI <1 by pretreatment with IFX and CT‐P13 maintained this status. The incidence of ADRs in this patient group was low and the drug survival rate was as high as 74%, even at 1 year, which was significantly higher than that in the naïve patient group (47%). Patients switched from other biologics for medical reasons (n = 16) responded similarly to biologic‐naïve patients, but drug survival was lower (24%). In conclusion, CT‐P13 showed excellent effectiveness as a first‐line therapy, no clinical difficulties in switching from IFX, and usefulness in patients who failed other biologics. CT‐P13 could be a cost‐effective alternative to IFX for the treatment of psoriasis.

As the 5G technology roll out continues, next generation dielectric layer materials are a major component of device packaging designs. The challenge is designing a material that provides a balance of characteristics to withstand the harsh environments and complex designs of the devices. Most importantly, the stability of the material is imperative to the performance of the packaged device. The next generation materials require a low dielectric loss (Df), low dielectric constant (Dk), and low moisture absorption whilst attaining the good mechanical and thermal properties to resist the inherent stresses in the final package. Additionally, emerging materials must be competitively priced and/or offer ease of manufacturability in order to offset current industry players and overcome the complexity of assembly. A novel low temperature curable, photo-patternable low Dk and low Df dielectric material is presented. PRL-29 offers a robust balance of characteristic properties that prove material stability and high reliability in simulated 5G conditions.

We investigated the effect of HfO2 film on the sensor response of a carbon nanotube thin film transistor (CNT-TFT) biosensor. Some parts of the CNT in the channel are suspended due to the formation of a network structure. The electrical noise of the CNT-TFT as a transducer is mainly caused by the structural fluctuation of the suspended CNTs in solution. We found that the electrical noise is dramatically reduced by introducing hafnium oxide (HfO2) film onto the CNT-TFT channel surface. This means that the HfO2 film has a suppression effect of fluctuation on the suspended CNTs and physical adsorption of the impurities such as non-specific molecules. We demonstrate that introducing HfO2 film is effective for the detection of thrombin molecules using the aptamer-modified CNT-TFT.

Telomere maintenance by telomerase activity supports the infinite growth of cancer cells. MST-312, a synthetic telomerase inhibitor, gradually shortens telomeres at non-acute lethal doses and eventually induces senescence and apoptosis of telomerase-positive cancer cells. Here we report that MST-312 at higher doses works as a dual inhibitor of telomerase and DNA topoisomerase II and exhibits acute anti-proliferative effects on cancer cells and xenografted tumours in vivo. Our cell-based chemical fingerprinting approach revealed that cancer cells with shorter telomeres and lower expression of lamin A, a nuclear architectural protein, exhibited higher sensitivity to the acute deleterious effects of MST-312, accompanied by formation of telomere dysfunction-induced foci and DNA double-strand breaks. Telomere elongation and lamin A overexpression attenuated telomeric and non-telomeric DNA damage, respectively, and both conferred resistance to apoptosis induced by MST-312 and other DNA damaging anticancer agents. These observations suggest that sufficient pools of telomeres and a nuclear lamina component contribute to the cellular robustness against DNA damage induced by therapeutic treatment in human cancer cells.

Abstract A novel polyfunctional benzoxazine monomer, OP‐a, is synthesized from aniline, formaldehyde, and an oligonuclear phenolic compound (OP) with a 4,4′‐dimethylenebiphenyl group as the phenol linker. After thermal curing of OP‐a up to 240 °C, a brown‐colored, transparent polybenzoxazine (POP‐a) film is obtained. The mechanical and thermal properties of the POP‐a film are investigated by tensile test, dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). The POP‐a film is extremely tough compared with a typical polybenzoxazine (PB‐a) film. The elongation at break of the POP‐a film is 7.6%, which is surprisingly large for the highly cross‐linked thermoset. The high cross‐link density is suggested from the very high storage modulus (over 1 GPa) above the glass transition temperature (T g) observed by DMA. The T g of POP‐a is also improved significantly to T g = 223 °C, which is approximately 50 °C higher than that of PB‐a. Moreover, TGA reveals that the thermal stability of POP‐a is also enhanced.