The FDA grants Accelerated Approval when deemed necessary to address an unmet need, with a promise that post-marketing research commitments will be fulfilled and that the approvals will be revisited and eventually changed if clinically meaningful results are reported. Herein, we present a timeline of all Accelerated Approvals granted to immune-checkpoint inhibitors to illustrate three ways in which the FDA has failed to fulfil their part in this social contract.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $19.83 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Rodriguez Fernandez, C. Are PD-1 and PD-L1 checkpoint inhibitors as good as we thought? Labiotech.eu https://labiotech.eu/features/pd-1-pd-l1-checkpoint-inhibitors/ (2018).
Tang, J. et al. The clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nat. Rev. Drug Discov. 17, 854 (2018).
Haslam, A. & Prasad, V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw. Open. 2, e192535–e192535 (2019).
FDA. Drugs@FDA: FDA Approved Drug Products. FDA.gov https://www.accessdata.fda.gov/scripts/cder/daf/ (2019).
Gyawali, B. & Kesselheim, A. S. Reinforcing the social compromise of accelerated approval. Nat. Rev. Clin. Oncol. 15, 596–597 (2018).
Merck. Merck provides update on KEYNOTE-240, a phase 3 study of KEYTRUDA® (pembrolizumab) in previously treated patients with advanced hepatocellular carcinoma [press release]. merck.com https://investors.merck.com/news/press-release-details/2019/Merck-Provides-Update-on-KEYNOTE-240-a-Phase-3-Study-of-KEYTRUDA-pembrolizumab-in-Previously-Treated-Patients-with-Advanced-Hepatocellular-Carcinoma/default.aspx (2019).
Merck. Merck provides update on phase 3 KEYNOTE-062 trial evaluating KEYTRUDA® (pembrolizumab) as monotherapy and in combination with chemotherapy for first-line treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma [press release]. merck.com https://investors.merck.com/news/press-release-details/2019/Merck-Provides-Update-on-Phase-3-KEYNOTE-062-Trial-Evaluating-KEYTRUDA-pembrolizumab-as-Monotherapy-and-in-Combination-with-Chemotherapy-for-First-Line-Treatment-of-Patients-with-Advanced-Gastric-or-Gastroesophageal-Junction-Adenocarcinoma/default.aspx (2019).
Bristol-Myers Squibb. Bristol-Myers Squibb announces phase 3 CheckMate -331 study does not meet primary endpoint of overall survival with Opdivo versus chemotherapy in patients with previously treated relapsed small cell lung cancer [press release]. bms.com https://news.bms.com/press-release/corporatefinancial-news/bristol-myers-squibb-announces-phase-3-checkmate-331-study-doe (2018).
Genentech. Genentech provides update on phase III study of TECENTRIQ (Atezolizumab) in people with previously treated advanced bladder cancer [press release]. gene.com https://www.gene.com/media/press-releases/14665/2017-05-09/genentech-provides-update-on-phase-iii-s (2017).
Staff, N. FDA alters approved use of two checkpoint inhibitors for bladder cancer. Cancer.gov https://www.cancer.gov/news-events/cancer-currents-blog/2018/bladder-cancer-checkpoint-inhibitor-change (2018).
Merck. Merck provides update on KEYNOTE-061, a phase 3 study of KEYTRUDA® (pembrolizumab) in previously treated patients with gastric or gastroesophageal junction adenocarcinoma [press release]. merck.com https://investors.merck.com/news/press-release-details/2017/Merck-Provides-Update-on-KEYNOTE-061-a-Phase-3-Study-of-KEYTRUDA-pembrolizumab-in-Previously-Treated-Patients-with-Gastric-or-Gastroesophageal-Junction-Adenocarcinoma/default.aspx (2017).
V.P. receives royalties from his book Ending Medical Reversal; his work is funded by the Laura and John Arnold Foundation; he has received honoraria for Grand Rounds/lectures from several universities, medical centres, nonprofit groups and professional societies; and he is a writer for Medscape and the host of the Plenary Session podcast, which receives crowdfunding support through the Patreon platform. J.G. declares no competing interests.