Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker–drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker–drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.

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Repurposing existing drugs for new uses: a cohort study of the frequency of FDA-granted new indication exclusivities since 1997

Journal of Pharmaceutical Policy and Practice ◽

10.1186/s40545-020-00282-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Babak Sahragardjoonegani ◽

Reed F. Beall ◽

Aaron S. Kesselheim ◽

Aidan Hollis

Keyword(s):

Therapeutic Potential ◽

Drug Repurposing ◽

Status Quo ◽

New Drugs ◽

Generic Entry ◽

Small Molecule Drugs ◽

Clinical Investigations ◽

Fda Approval ◽

Limited Duration ◽

Observation Period

Abstract Background Drug repurposing (i.e., finding novel uses for existing drugs) is essential for maximizing medicines’ therapeutic utility, but obtaining regulatory approval for new indications is costly. Policymakers have therefore created temporary indication-specific market exclusivities to incentivize drug innovators to run new clinical investigations. The effectiveness of these exclusivities is poorly understood. Objective To determine whether generic entry impacts the probability of new indication additions. Methods For a cohort of all new small-molecule drugs approved by the FDA between July 1997 and May 2020, we tracked new indications added for the subset of drugs that experienced generic entry during the observation period and then analyzed how the probability of a new indication changed with the number of years since/to generic entry. Results Of the 197 new drugs that subsequently experienced generic entry, only 64 (32%) had at least one new indication added. The probability of a new indication addition peaked above 4% between 7 and 8 years prior to generic entry and then to dropped to near zero 15 years after FDA approval. We show that the limited duration of exclusivity reduces the number of secondary indications significantly. Conclusion Status quo for most drug innovators is creating novel one-indication products. Despite indication-specific exclusivities, the imminence of generic entry still has a detectable impact on reducing the chances of new indication additions. There is much room for improvement when it comes to incentivizing clinical investigations for new uses and unlocking existing medicines’ full therapeutic potential.

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Ranbaxy Laboratories has received US FDA approval for the manufacture and marketing of cefuroxime axetil for oral suspension USP

Inpharma Weekly ◽

10.2165/00128413-200816250-00063 ◽

2008 ◽

Vol &NA; (1625) ◽

pp. 22

Author(s):

&NA;

Keyword(s):

Cefuroxime Axetil ◽

Oral Suspension ◽

Fda Approval ◽

Us Fda

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Single-arm oncology trials and the nature of external controls arms

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2021-0003 ◽

2021 ◽

Author(s):

Mustafa Hashmi ◽

Jeremy Rassen ◽

Sebastian Schneeweiss

Keyword(s):

Secondary Data ◽

Outcome Data ◽

Aggregate Data ◽

Primary Data ◽

External Control ◽

Calendar Time ◽

Convenience Sample ◽

Fda Approval ◽

Baseline Characteristics ◽

Us Fda

Aim: Single-arm trials with external control arms (ECAs) have gained popularity in oncology. ECAs may consist of primary data from previous trials, electronic health records (EHRs) or aggregate data from the literature. We sought to provide a description of how such studies achieve similarity of patients, comparability of data quality and outcome assessment. Materials & methods: In a stratified convenience sample of 15 studies, five used primary data from trials as ECAs, five used secondary data from EHRs and five used aggregate data from the literature. Data were collected from the published literature and public web resources, blinded to the eventual approval decision. Results: Studies using ECAs from primary data and EHR data displayed methods to achieve comparability of information, including matched baseline characteristics. Aggregate data from published studies did not attempt to match covariates. The EHR controls often showed calendar time overlap for collecting information while trial data were mostly historic. Outcome data were not consistently reported across studies. US FDA approval was only seen when primary data from trials or EHR data were used as the ECA, however no ECA in this sample directly contributed to approval. Discussion: In this nonsystematic review of ECAs for single-arm trials, the ECAs derived from primary data collected by other trials or EHRs show patterns of patient comparability, time overlap, and realistic methodological approaches to achieving balance between treatment arms. They are often submitted to regulators while literature-derived aggregate findings as ECA may serve as benchmarks for pipeline decisions.

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Luspatercept in the treatment of lower-risk myelodysplastic syndromes

Future Oncology ◽

10.2217/fon-2020-1093 ◽

2021 ◽

Author(s):

Onyee Chan ◽

Rami S Komrokji

Keyword(s):

Clinical Trials ◽

Myelodysplastic Syndromes ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Safety Data ◽

Erythroid Differentiation ◽

Fda Approval ◽

The Us ◽

Us Fda ◽

Terminal Erythroid Differentiation

Transforming growth factor beta (TGF-β) signaling pathway is key to hematopoiesis regulation. Increased activation of this pathway contributes to ineffective terminal erythroid differentiation in myelodysplastic syndromes (MDS). Luspatercept is a novel fusion protein that traps TGF-β ligands preventing them from binding to Type II TGF-β receptors, thereby decreasing phosphorylated SMAD2/3 resulting in the downstream effect of promoting erythropoiesis. Seminal clinical trials using luspatercept, PACE-MD and MEDALIST, demonstrated impressive efficacy in the treatment of transfusion-dependent anemia in intermediate risk or lower MDS had led to the US FDA approval for this indication. This review summarizes luspatercept mechanisms of action, efficacy/safety data supporting its use and ongoing clinical trials in MDS.

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New Drugs Approved by the FDA/New Dosage Forms and Indications Approved by the FDA/Agents Pending FDA Approval/Significant Labeling Changes or “Dear Health Professional” Letters Related to Safety

Hospital Pharmacy ◽

10.1310/hpj4505-404 ◽

2010 ◽

Vol 45 (5) ◽

pp. 404-417

Author(s):

Danial E. Baker

Keyword(s):

Health Professional ◽

Dosage Forms ◽

New Drugs ◽

Fda Approval

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New Drugs Approved by the FDA New Dosage Forms and Indications Agents Pending FDA Approval Labeling Changes Related to Safety

Hospital Pharmacy ◽

10.1177/001857870103601209 ◽

2001 ◽

Vol 36 (12) ◽

pp. 1278-1289

Author(s):

Danial E. Baker

Keyword(s):

Dosage Forms ◽

New Drugs ◽

Fda Approval ◽

New Information ◽

Bold Type

This monthly feature will help readers keep current on new drugs, new indications and dosage forms, and safety-related changes in labeling or use. Each month, new information will be added to the table (shown in bold type) and older information will be removed. Efforts have been made to ensure the accuracy of the information; however, if there are any questions, let us know at [email protected] .

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