Patents and Regulatory Exclusivities on GLP-1 Receptor Agonists

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.

Figure 1:

GLP-1 receptor agonists included in the cohort

Figure 2:. Protection from patents and regulatory exclusivities on GLP-1 receptor agonists, 1993-2038

This figure shows the expected duration of protection from generic competition on each GLP-1 receptor agonist from the time of first patent filing until the expiration of the last patent or regulatory exclusivity. The dark blue bars (uppermost for each product) represent protection for the product as a whole, while the light blue bars represent protection for each of the product’s individual strengths and/or formulations. Products are listed in ascending order based on the initial Food and Drug Administration (FDA) approval date for a given product. Manufacturers may add new patents in subsequent years, which could expire later than patents depicted in the figure. The median total duration of protection from FDA approval among GLP-1 receptor agonists is 18.3 years (IQR: 16.0-19.4). The median time elapsed from the earliest patent filing date within a given product to the expiration date of the last-to-expire patent or exclusivity on that product is 31.9 years (IQR: 29.9-36.6).

Figure 3:. Key legal events in the patent lifecycles of GLP-1 receptor agonists

This figure shows the distribution of key legal events associated with the patent life cycle (priority date, filing date, granting date, and expiration date) for each patent in the cohort relative to the corresponding product’s approval date. Boxes represent the interquartile range (IQR) with vertical lines in each box depicting the median, and whiskers extend in either direction from the first and third quartiles by up to 1.5-times the IQR. There were 186 total patents listed on the 10 products in the cohort, and each of the 4 plots depicts the relevant legal event for all patents in the cohort. Of note, this figure excludes patents (n=7) that were removed from the Orange Book prior to expiration since these patents do not contribute to expected periods of patent protection (primary endpoint).