Proceedings: DIA China 2020

Driving Co-Development ofTherapeutic Drugs andCompanion Diagnostics

Increased RegulatoryFocus on PrecisionMedicine in ChinaJennifer ShengJennifer Sheng Ningxia Western Cloud Data Technology Co. Ltd.Ningxia Western Cloud Data Technology Co. Ltd.

R apid development of personalized (also known asprecision) medicine has made separating patientsinto different groups and customizing treatments

or products based on their genomic information animportant trend.

Development of companion diagnostics (CDx) as powerful tools in precision medicinetypically follows one of three pathways: co-development, bridging, and follow-on. Co-development is the most ideal and cost-effective CDx pathway: It is conducive toscreening target patients speci�cally and identifying drug targets accurately, reducingdevelopment cost and cycle times for pharmaceutical companies. The DIA China 2020session Driving Co-Development of Therapeutic Drugs and Companion Diagnostics forPrecision Medicine and Optimizing the Clinical Trial Design reviewed the regulatoryframework for drug and diagnostic co-development and how to overcome the inevitablehurdles to quickly delivering innovative drugs and diagnostics to patients.

Key Takeaways

The US, EU, and China each have their own CDx regulatory policies. The US entered

the global CDx market earlier than the other two, and also has the most established

CDx regulatory documentation and history. Regulatory policy in the US is established

by the FDA. Regulatory policies for CDx in the EU are in a transition period.

Although CDx regulation in China is less advanced than in the US, the National

Medical Products Administration (NMPA) has paid increasing attention to regulatory

guidelines for CDx development and encourages co-development based on the

Technical Review Guideline of Clinical Trial for Co-Development of CDx Reagentsand Anti-Tumor Drugs, which China’s Center for Medical Device Evaluation (CMDE)

announced on June 3, 2020.

Drug and CDx co-developers need early planning and engagement to accelerate

regulatory approvals and reduce costs.

Data available from FDA show that 25 percent (11 of 44) of therapeutic NME medicinalproduct approvals in 2019 are considered personalized medicines; NMEs as personalizedmedicines increased from 21 percent in 2014 to 42 percent in 2018. In Europe,approximately 30 percent of NMEs approved from January to August 2020 required adiagnostic test for patient identi�cation. Pairing diagnostic tests that can determine anindividual patient’s responsiveness to therapeutic options can improve the drugdevelopment process. Drug and CDx ef�cacy are essential to the practice of precisionmedicine.

CDx are de�ned by the FDA as tests that are required for the safe and effective use of adrug. In 2014, FDA issued Guidance for Industry: In Vitro Companion Diagnostic Devicesto inform diagnostic developers that CDx can be indicated for a group of therapeuticproducts, instead of one particular drug, if there is suf�cient data to support such labeling.In 2016, FDA issued the draft guidance Principles for Co-Development of an In VitroCompanion Diagnostic Device with a Therapeutic Product as a practical guide to assisttherapeutic product sponsors and in vitro diagnostic device (IVD) sponsors in developinga therapeutic product with an accompanying IVD companion diagnostic (a processreferred to as co-development). In April 2020, FDA published a �nal guidance Developingand Labeling In vitro Companion Diagnostic Devices for a Speci�c Group of OncologyTherapeutic Products, which lists several key FDA considerations for CDx manufacturersconsidering a class-based label and clari�es the process required to apply for and begranted one.

CDx regulatory policies in the EU are in transition. Regulation 2017/746 on in vitrodiagnostic medical devices (IVDR) entered into force in Europe and will be fully effectiveon May 26, 2022. This regulation establishes the �rst European regulatory link between theapproval of drugs and CDx.

Despite the fast-growing market for CDx products, China has no published CDx-speci�cregulatory guidelines and no clear regulatory de�nition of CDx-related products. Most ofthese types of related products have been registered as Class III medical devices andapproved based on current medical device and IVD regulations. China’s CMDE (a divisionof NMPA) announced the preparation of the Technical Review Guideline of Clinical Trialfor Co-Development of CDx Reagents and Anti-Tumor Drugs in June 2020. Thisencouraged co-development between discovery research laboratories andpharmaceutical companies. In July 2020, China’s CMDE published the draft version ofGuidelines for Package Insert Update and Technical Review of CDx for the Same Kind ofTherapeutic Drug. In August 2020, CMDE issued the draft Guidance for Clinical Study ofCDx for the Marketed Oncology Drugs. These national guidelines and regulationscontinue to create favorable conditions for development of drug–CDx reagents in China.

Co-developing drugs and diagnostics can accelerate their respective regulatory approvalswhile reducing costs. However, many pharmaceutical companies seem to ignore theregistration of CDx. Because this CDx application and registration period will takeapproximately three years, the best practice is for drug and diagnostic developers to pair

up early and develop a strategy that considers the policies of global regulatory bodies aswell as each stage in the process, from development through testing, up to access andadoption.

Unlike drug products, CDx products have not fully entered the Chinese market; as a result,real world CDx studies, such as bridging studies and follow-on pathways, are often notsuitable in these situations. However, real world studies may offer a new pathway for CDxdevelopment as more products enter the market in China.

Drug–diagnostic co-development integrates the biopharmaceutical and diagnosticlandscapes and is at the forefront of ongoing work by discovery research laboratories,pharmaceutical companies, and regulatory bodies. Development and improvement ofregulatory policies will present more options for drug–diagnostic co-development andbring a more promising future for pharmacotherapy and patient care in China.

References available upon request.