TY - JOUR

T1 - Analysis of the Authorized Target Populations for Fixed Dose Combination Products Between 2000 and 2017 Reveals Discrepancies Between EMA's and FDA's Views on Initial Dual-Therapy

AU - Bjerrum, Ole Jannik

AU - Eichendorff, Sascha

AU - Alkis, Nada Bassam

PY - 2020/3

Y1 - 2020/3

N2 - Background: A fixed dose combination (FDC) product containing two components can be authorized for the use in 3 conceptual scenarios (1) as substitution for a treatment regimen containing both components given separately (substitution therapy) or (2) as replacement for a treatment regimen where the patient currently receives one of the components (add-on therapy) or (3) initial treatment of patients naive to both components (initial combination therapy). Method: Trends in European Medicine Agency (EMA) and Food and Drug Administration (FDA) approvals of FDC products for the 3 scenarios were explored by comparing the therapeutic indications retrieved from the EMA and FDA websites for FDCs approved between January 2000 and April 2017 within 5 selected therapeutic areas: type 2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease, hypertension, and human immunodeficiency virus (HIV) infection. Result: Approval decisions between EMA and FDA were largely aligned for the substitution therapy and add-on therapy scenarios. Discrepancies were found for the initial combination therapy scenario. Conclusion: Since EMA and FDA rely on similar conceptional models when approving FDCs, the reasons behind this general disparity are not clear, but may be found in the lack of evidence from the registration studies. Sponsors and health authorities should work collaboratively on closing that gap.

AB - Background: A fixed dose combination (FDC) product containing two components can be authorized for the use in 3 conceptual scenarios (1) as substitution for a treatment regimen containing both components given separately (substitution therapy) or (2) as replacement for a treatment regimen where the patient currently receives one of the components (add-on therapy) or (3) initial treatment of patients naive to both components (initial combination therapy). Method: Trends in European Medicine Agency (EMA) and Food and Drug Administration (FDA) approvals of FDC products for the 3 scenarios were explored by comparing the therapeutic indications retrieved from the EMA and FDA websites for FDCs approved between January 2000 and April 2017 within 5 selected therapeutic areas: type 2 diabetes mellitus (T2DM), asthma, chronic obstructive pulmonary disease, hypertension, and human immunodeficiency virus (HIV) infection. Result: Approval decisions between EMA and FDA were largely aligned for the substitution therapy and add-on therapy scenarios. Discrepancies were found for the initial combination therapy scenario. Conclusion: Since EMA and FDA rely on similar conceptional models when approving FDCs, the reasons behind this general disparity are not clear, but may be found in the lack of evidence from the registration studies. Sponsors and health authorities should work collaboratively on closing that gap.

KW - regulatory approval

KW - regulatory science

KW - prescription drug labeling

KW - therapeutic indication

KW - add-on therapy

KW - substitution therapy

U2 - 10.1007/s43441-019-00057-7

DO - 10.1007/s43441-019-00057-7

M3 - Journal article

C2 - 32072578

VL - 54

SP - 297

EP - 302

JO - Therapeutic Innovation & Regulatory Science

JF - Therapeutic Innovation & Regulatory Science

SN - 2168-4790

IS - 2

ER -