The 2018 Nobel Prize in Medicine for breakthroughs in targeting immune checkpoint inhibitors: a brief perspective

Rios, Adan; Salazar, Georgina To’a; Zhang, Ningyan; An, Zhiqiang

doi:10.1093/abt/tbz003

Cited by 2 publications

(2 citation statements)

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“…A series of policies were released by the government to encourage the development of biomedicine. Since immune checkpoint therapy won the Nobel Prize in 2018 (18), immune checkpoint inhibitor monoclonal antibodies have gained much attention in China. However, the targets of drugs were limited to cytotoxic T lymphocyte-associated protein 4, programmed cell death 1, and its ligand in the Chinese biopharmaceutical firms.…”

Section: Development Of Biopharmaceuticalsmentioning

confidence: 99%

Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011–2020)

et al. 2021

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Background: In recent years, the number of clinical trials initiated in China has increased rapidly. The aim of this study was to overview the changing landscape of phase I clinical trials in mainland China from 2011 to 2020.Methods: We analyzed phase I clinical trials registered on 3 websites including the Chinese Clinical Trial Registry, ClinicalTrials.gov, and the China National Medical Products Administration Center for Drug Evaluation platform.Findings: A total of 2,842 phase I clinical trials were posted from January 1, 2011, to December 31, 2020. The overall number of clinical trials for innovative drugs was 1,497, accounting for half of all the phase I clinical trials (53%). Among these 1,486 innovative drug clinical trials, 924 were newly tested drugs with an average annual growth rate of 59%. Biological drug research increased significantly from 22.6% during 2011–2015 to 33.3% during 2016–2020. These principal investigators (PIs) of these clinical trials were mainly from Beijing (n = 871), followed by Shanghai (n = 496) and Jiangsu (n = 281). As for the therapeutic area of phase I clinical trials, cancer took up the most percentage of all the clinical trials (35%), followed by infectious disease (9%), nervous system disease (9%), etc. Most phase I clinical trials are conducted on healthy volunteers (n = 1,642, 57.8%), some cancer drugs are conducted in patients with cancer (n = 846, 29.8%), and only a few clinical trials were conducted in the elderly (n = 7). Among these clinical trials of the newly tested innovative drugs, the first in human (FIH) clinical trials accounted for 82% (744), and the First in Chinese (FIC) clinical trials only took up 18% (167). Only a small number of drugs could be made the transition to phase II (n = 207, 22%). In addition, despite the number of newly tested drugs during 2011–2015 (n = 163) was much less than that in 2016–2020 (n = 761), the percentage of drugs that could enter into phase II clinical trials in 2011–2015 (34%) was higher than that in 2016–2020 (20%).Conclusion: In the past 10 years, the development of phase I clinical trials has achieved great progress in mainland China due to the novel design and drug innovation policy. Nevertheless, future efforts are needed to make for improving the phase transition success rate of innovative drugs.

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Section: Development Of Biopharmaceuticalsmentioning

confidence: 99%

Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011–2020)

et al. 2021

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“…Immune checkpoint inhibitors (ICI) have truly become an important mainstay of anticancer therapy since initial introduction in 2011 [ 1 ]. However, concomitant with the rise of immune checkpoint blockade has also emerged a set of side effects known as immune-related adverse events (irAEs) [ 2 , 3 ].…”

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confidence: 99%

Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV

Hughes

Pietropaolo

Vasudevan

et al. 2020

Journal of the Endocrine Society

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Immune checkpoint inhibitor–associated diabetes mellitus (ICI-DM) is a known immune-related adverse event (irAE) following treatment with programmed cell death protein 1 (PD-1), with a reported 0.9% incidence. We hereby present the first case, to our knowledge, of ICI-DM following ICI use in a human immunodeficiency virus (HIV) patient. In this case, a 48-year-old man with HIV stable on highly active antiretroviral therapy (HAART) was diagnosed with Hodgkin lymphoma and initiated treatment with the PD-1 inhibitor nivolumab. His lymphoma achieved complete response after 5 months. However, at month 8, he reported sudden polydipsia and polyuria. Labs revealed a glucose level of 764 mg/dL and glycated hemoglobin A1c (HbA1c) of 7.1%. Low C-peptide and elevated glutamic acid decarboxylase 65 (GAD65) antibody levels confirmed autoimmune DM, and he was started on insulin. Major histocompatibility complex class II genetic analysis revealed homozygous HLA DRB1*03-DQA1*0501-DQB1*02 (DR3-DQ2), which is a known primary driver of genetic susceptibility to type 1 DM. Autoimmune DM has been reported as an ICI-associated irAE. However, patients with immunocompromising conditions such as HIV are usually excluded from ICI trials. Therefore, little is known about such irAEs in this population. In this case, risk of ICI-DM as an irAE was likely increased by several factors including family history, a high-risk genetic profile, islet-related immunologic abnormalities, active lymphoma, and HIV infection with a possible immune reconstitution event. Clinicians should maintain a high index of suspicion for development of irAEs associated with ICI, particularly as use of these therapies broadens. Thorough investigation for presence of higher-risk features should be conducted and may warrant inclusion of pre-therapy genetic and/or autoantibody screening.

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The 2018 Nobel Prize in Medicine for breakthroughs in targeting immune checkpoint inhibitors: a brief perspective

Cited by 2 publications

References 36 publications

Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011–2020)

Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011–2020)

Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV

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