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Diabetes

Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists

To identify the key insights or developments described in this article

1 Credit CME

JAMA

Published Online: July 28, 2023

Special Communication

Article Information and Disclosures

Rasha Alhiary, PharmD^1,2;

Aaron S. Kesselheim, MD, JD, MPH²;

Sarah Gabriele, LLM, MBE²;

Reed F. Beall, PhD³;

S. Sean Tu, JD, PhD⁴;

William B. Feldman, MD, DPhil, MPH^2,5

Author Affiliations

¹School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania
²Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
³Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
⁴West Virginia University College of Law, Morgantown
⁵Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts

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Key Points

Question How have manufacturers of brand-name glucagon-like peptide 1 (GLP-1) receptor agonists used the patent and regulatory system to extend periods of market exclusivity?

Findings Brand-name manufacturers obtained a median of 19.5 patents per GLP-1 receptor agonist and secured a median of 18.3 years of expected protection; more than half of all patents were obtained on the delivery devices rather than active ingredients. No generic competition has yet emerged on these products.

Meaning Long periods of market exclusivity on GLP-1 receptor agonists underscore the need for patent and regulatory reform on drug-device combinations.

Abstract

Importance Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive.

Objective To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity.

Evidence Review The annual US Food and Drug Administration’s (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity.

Findings On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval.

Conclusions and Relevance Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.

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Article Information

Accepted for Publication: July 6, 2023.

Published Online: July 28, 2023. doi:10.1001/jama.2023.13872

Corresponding Author: William B. Feldman, MD, DPhil, MPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, 1620 Tremont St, Ste 3030, Boston MA 02120 (wbfeldman@bwh.harvard.edu).

Author Contributions: Drs Alhiary and Feldman had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kesselheim, Beall, Feldman.

Acquisition, analysis, or interpretation of data: Alhiary, Kesselheim, Gabriele, Tu, Feldman.

Drafting of the manuscript: Alhiary, Beall.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Alhiary, Feldman.

Obtained funding: Kesselheim, Feldman.

Administrative, technical, or material support: Beall, Tu, Feldman.

Supervision: Kesselheim, Feldman.

Conflict of Interest Disclosures: Dr Kesselheim reported serving as an expert witness in litigation against Gilead relating to tenofovir-containing products outside the submitted work. Dr Feldman reported serving as an expert witness in litigation against inhaler manufacturers and as a consultant for Alosa Health and Aetion outside the submitted work. No other disclosures were reported.

Funding/Support: This work was funded by the Commonwealth Fund. The work of Drs Kesselheim and Feldman was also supported by funding from Arnold Ventures, Dr Tu’s from West Virginia University’s Hodges Research Grant, and Dr Feldman’s from the National Heart, Lung, and Blood Institute (K08HL163246).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
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