On 7 April 2020, China’s Center for Drug Evaluation (CDE) published draft guidance on clinical trials for the approval of bevacizumab copy biologicals. This guidance is the second specific guideline released by the CDE in April. The agency also released guidance on adalimumab on 1 April 2020 .
The CDE, which is part of the National Medical Products Administration (NMPA), formerly the China Food and Drug Administration (CFDA, 国家食品药品监督管理局) – the Chinese authority that oversees all drug manufacturing, trade and registration in the country – has released the draft guidance for a one-month consultation period.
Guiding Principles for Clinical Trials of Bevacizumab Copy Biologicals
Date: April 2020
The draft guidance follows the format of the adalimumab guidance in outlining how companies should conduct pharmaceutical, non-clinical and clinical comparison trials in stages ‘using a step-by-step sequence’.
Bevacizumab is a humanized monoclonal antibody. It inhibits angiogenesis (the formation of new blood vessels) by blocking the action of vascular endothelial growth factor A (VEGF-A). Bevacizumab can therefore slow the growth of new blood vessels in tumours and is used to treat various cancers, including colorectal, lung, breast, glioblastoma, kidney and ovarian. The patents on the originator product, Roche’s Avastin (bevacizumab), expired in the US in July 2019 and will expire in Europe in January 2022 .
The draft guidance covers how to perform pharmacokinetic comparisons in healthy subjects and assess clinical effectiveness in patients. The guidance refers back to the overarching guidance on the clinical study of copy biologicals in China , but also features issues specific to bevacizumab and cancer patients taking bevacizumab.
The draft guidance recommends following one of three strategies for the patient population and endpoint for assessing clinical safety and effectiveness in patients:
Population: metastatic non-squamous non-small cell lung cancer (NSCLC) patients
Primary endpoint: objective response rate (ORR) as a relatively insensitive endpoint
Comparator: head-to-head equivalence study with the originator biological, Avastin
Population: domestically approved indications
Primary endpoint: progression free survival (PFS) or overall survival (OS)
Comparator: other optional standard treatments other than Avastin
Population: indications approved abroad but not approved in China, such as kidney cancer, ovarian cancer
Primary endpoint: PFS or OS
Comparator: current standard treatment of target indications
- Population: indications that are not approved at home and abroad for clinical research, such as macular degeneration of the retina.
The draft guidance does, however, point out that option 1 is the method most commonly chosen by current R & D companies and is the recommended clinical development strategy for bevacizumab copy biologicals. This is also the only route to extrapolation of indications.
Other bevacizumab-specific issues discussed in the guidance include the criteria for selecting study subjects, dose/dosing regimen and route of administration, combination with chemotherapy drugs, endpoints, boundary value selection and sample size calculation, as well as safety and immunogenicity studies for bevacizumab.
The draft will be a welcome addition to the guidance on copy biologicals already published by the CDE . Chinese companies known to be working on copy biologicals of bevacizumab include Bio-Thera Solutions, Innovent Biologics, Mabworks, Qilu Pharmaceutical, Shanghai Henlius Biotech (Fosun Pharma) and TOT Biopharm . In fact, the NMPA approved Qilu Pharmaceutical’s bevacizumab copy biological Ankada (QL-1101) in January 2020 .
The CDE is accepting feedback on the draft guidance until 7 May 2020.
Copy biologicals approved in China
1. GaBI Online - Generics and Biosimilars Initiative. China publishes draft guideline for adalimumab copy biologicals [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 8]. Available from: www.gabionline.net/Guidelines/China-publishes-draft-guideline-for-adalimumab-copy-biologicals
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of bevacizumab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 8]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-of-bevacizumab
3. GaBI Online - Generics and Biosimilars Initiative. Chinese guidelines for copy biologicals [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 8]. Available from: www.gabionline.net/Guidelines/Chinese-guidelines-for-copy-biologicals
4. GaBI Online - Generics and Biosimilars Initiative. China approves bevacizumab copy biological Ankada [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 May 8]. Available from: www.gabionline.net/Biosimilars/News/China-approves-bevacizumab-copy-biological-Ankada
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