Toward Optimum Benefit‐Risk and Reduced Access Lag For Cancer Drugs in Asia: A Global Development Framework Guided by Clinical Pharmacology Principles

[...]although the lack of clinically meaningful ethnic sensitivity in the major Asian ethnicities relative to Western populations may permit seamless consideration and integration of the entire continent as a whole in global drug development, the converse may not be true as differences in drug dispo...

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Bibliographic Details
Published in:Clinical and translational science 2016-02, Vol.9 (1), p.9-22
Main Authors: Venkatakrishnan, K, Burgess, C, Gupta, N, Suri, A, Takubo, T, Zhou, X, DeMuria, D, Lehnert, M, Takeyama, K, Singhvi, S, Milton, A
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Asia
Body size
Cancer therapies
Clinical trials
Computer simulation
Dosage
Dose-Response Relationship, Drug
Drug development
Drug dosages
Employees
Feedback
Health risks
Health Services Accessibility
Humans
Neoplasms - drug therapy
Nonlinear systems
Oncology
Patients
Payloads
Pharmaceutical industry
Pharmaceuticals
Pharmacology
Practice Guidelines as Topic
Regional development
Registration
Review
Risk Assessment
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Summary:[...]although the lack of clinically meaningful ethnic sensitivity in the major Asian ethnicities relative to Western populations may permit seamless consideration and integration of the entire continent as a whole in global drug development, the converse may not be true as differences in drug disposition, PK/PD properties, and consequently dosage requirements between Asian (i.e., Chinese, Korean, and Japanese) and Western populations cannot be assumed to directly apply to other highly heterogeneous sections of Asia, such as the Indian subcontinent, Malaysia, or Indonesia. [...]when an exposure‐matched regional dosing approach is used in a global phase III trial, it is important to seek feedback from regulatory authorities across regions, with the rationale for the proposed approach described and positioned based on the supporting data. In the case of antibody therapeutics (i.e., simple unconjugated antibodies without small molecule payloads), the risk for inter‐ethnic differences is low and population PK modeling and simulation provides the opportunity to predict potential differences in PK secondary to body size differences between Asian and Western populations. [...]based on the extent of PK nonlinearity related to target‐mediated drug disposition, safety profile, and therapeutic index of the antibody in the clinical dose range based on Western experience, the level of risk for inter‐ethnic differences in dosage can be estimated. [...]decisions regarding appropriate options and selection of an optimal strategy should be informed by cross‐functional and cross‐regional considerations involving all major scientific, clinical development, regulatory, pharmaceutical manufacturing, and commercial functions in the global pharmaceutical company setting, with appropriate global regulatory feedback obtained from health authorities before trial initiation.
ISSN:1752-8054
1752-8062
DOI:10.1111/cts.12386