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Respiratory Diseases

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Most used technologies in drug development

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Disease Domain	Count

Infectious Diseases	4

Top 5 Drug Type	Count

Small molecule drug	4

Top 5 Target	Count

SARS-CoV-2 3CLpro(SARS-CoV-2-3C-like-proteinase)	2
SARS-CoV-2 Mpro(SARS-CoV-2 main protease)	2

Although previous studies have shown no increased mortality risk after the primary series of COVID-19 mRNA vaccines, reports on booster doses are lacking. This study aimed to evaluate mortality risk after the mRNA vaccine boosters in addition to the primary series. This nested case-control study included two age-specific cohorts (18-64 and ≥65 years as of February 1, 2021) in two municipalities. All deaths were identified and matched five controls for each case at each date of death (index date) with risk set sampling according to municipality, age, and sex. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for mRNA vaccines (first to fifth doses) were estimated by comparing with no vaccination within 21 and 42 days before the index date using a conditional logistic regression model. The 18-64-years cohort comprised 431 cases (mean age, 57.0 years; men, 58.2%) and 2,155 controls (mean age, 56.0; men, 58.2%), whereas the ≥65-years cohort comprised 12,166 cases (84.0; 50.2%) and 60,830 controls (84.0, 50.2%). The aORs (95% CI) in 0-21 days after the third and fourth doses in the 18-64-years cohort were 0.62 (0.24, 1.62) and 0.38 (0.08, 1.84), respectively. The aORs (95% CI) after the third to fifth doses in the ≥65 years cohort were 0.36 (0.31, 0.43), 0.30 (0.25, 0.37), and 0.26 (0.20, 0.33), respectively. In conclusion, booster doses of mRNA vaccines do not increase mortality risk. These findings could help subsequent vaccine campaigns and alleviate vaccine hesitancy.

01 Dec 2024·Regenerative Therapy

Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial

Article

Author: Nakamura, Toru ; Fujimori, Yoshihiro ; Fukami, Kei ; Yoh, Kazunori ; Kobayashi, Kaoru ; Yamahara, Kenichi ; Tanizawa, Kyoko ; Yamakado, Koichiro ; Ioji, Tetsuya ; Suzuki, Hiroyuki ; Yamamoto, Hidekazu ; Kako, Makoto ; Ohtake, Takayasu ; Takashima, Tomoyuki ; Kako, Yasukazu ; Kaibori, Masaki ; Torimura, Takuji ; Masuda, Atsutaka ; Uojima, Haruki ; Nagafuji, Koji ; Kawaguchi, Takumi ; Fujita, Yasuyuki ; Enomoto, Hirayuki ; Yoshihara, Satoshi ; Koga, Hironori ; Nishiguchi, Shuhei ; Kobayashi, Shuzo ; Hazama, Takuma ; Tsukiyama, Toshitaka ; Kawamoto, Atsuhiko ; Iwamoto, Hideki

IntroductionIn this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34⁺ cells compared with standard therapy in patients with decompensated cirrhosis type C.MethodsPatients were randomly assigned (2:1) to the CD34⁺ cell transplant (CD34⁺ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment.ResultsFourteen patients (CD34⁺ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34⁺ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34⁺ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34⁺ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34⁺ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34⁺ cell group. No patients died and no hepatocellular carcinoma occurred within the study period.ConclusionsPB-CD34⁺ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

01 Dec 2024·Journal of Infection and Chemotherapy

Comparison of the effects of cefmetazole and meropenem on microbiome: A pilot study

Article

Author: Fukui, Yuto ; Nagata, Naoyoshi ; Kato, Hideaki ; Miyoshi-Akiyama, Tohru ; Komatsubara, Mika ; Inagaki, Takeshi ; Koizumi, Ryuji ; Takemoto, Norihiko ; Kamegai, Kohei ; Ashida, Shinobu ; Hirose, Keika ; Nomoto, Hidetoshi ; Kobayashi, Kentaro ; Inada, Makoto ; Ohmagari, Norio ; Saito, Sho ; Hayakawa, Kayoko ; Ide, Satoshi ; Endo, Mio ; Hashimoto, Takehiro

BACKGROUNDCefmetazole (CMZ) is a carbapenem-sparing option in the treatment of extended-spectrum beta-lactamase (ESBL)-producing bacterial infection. In this pilot study, we aimed to compare the effects of antimicrobial treatment (meropenem [MP] and CMZ) with those of no antimicrobial treatment (control group) on the microbiome.METHODSThe study was a multicenter, prospective, observational pilot study conducted from October 2020 to October 2022. Feces and saliva samples were collected for microbiome analyses at two time points (early-period: days 1-3; and late-period: days 4-30) for the antimicrobial treatment group, and at one time point for the control group.RESULTSFive feces (MP-F and CMZ-F) and five saliva (MP-S and CMZ-S) samples were included in the MP and the CMZ groups. Ten feces (C-F) and saliva (C-S) samples were included in the control group. Group α diversity was notably lower in the late-period MP-F group than the control group as determined with the Shannon richness index. β diversity analysis of the feces samples based on weighted and unweighted UniFrac distances revealed distinctions in both the late-period CMZ-F and MP-F groups compared with the control group. Weighted UniFrac analysis showed that only the early-period MP-F group differed from the control group. In the saliva samples, weighted and unweighted UniFrac analyses showed significant differences between the control group and the early CMZ, late CMZ, and late MP groups.CONCLUSIONSMP treatment may cause larger impact on the feces microbiome than CMZ in Japanese patients.

100 Deals associated with National Center for Global Health & Medicine

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100 Translational Medicine associated with National Center for Global Health & Medicine

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Pipeline

Pipeline Snapshot as of 23 Dec 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

SARS-CoV-2 Mpro inhibitors 5h(National Center for Global Health & Medicine) ( SARS-CoV-2 Mpro )	COVID-19 More	Preclinical
GRL-0820 ( SARS-CoV-2 3CLpro )	COVID-19 More	Preclinical
GRL-0920 ( SARS-CoV-2 3CLpro )	COVID-19 More	Preclinical
GRL-1720 ( SARS-CoV-2 Mpro )	COVID-19 More	Preclinical