Crystal’s Perspective: Polymorph Patent Landscape of 28 FDA-Approved Small Molecule Drugs in 2024

In 2024, the U.S. Food and Drug Administration (FDA) approved a total of 50 new drugs ^[1], including 34 new molecular entities (NMEs). Among these, 28 were classified as small molecule drugs. An analysis of their administration routes and dosage forms shows that 4 were liquid formulations (comprising 3 injectable solutions and 1 oral solution), 2 were suspensions (1 inhalation and 1 oral), and 22 were solid or semi-solid formulations. The solid/semi-solid group includes 20 solid oral dosage forms and 2 gel-based formulations. A detailed summary is presented in Table 1.

Table 1. Overview of the 34 New Molecular Entities Approved by the FDA in 2024

An analysis of the patent strategies associated with the 22 solid and semi-solid formulation drugs revealed that 15 products—including those with pending applications—have incorporated polymorph patents. This represents approximately 68% of all small-molecule drugs in this category. Further details are provided in Table 2.

Table 2. Overview of Polymorph Patent Strategies for 22 Solid and Semi-Solid Small Molecule Drugs Approved by the FDA in 2024

For the 15 small-molecule drugs identified above with originator-filed polymorph patent strategies, we further analyzed the expiration dates of their compound and polymorph patents, as well as the time intervals between them. The findings are summarized in Table 3. Two products with polymorph patents still under regulatory examination were excluded from the statistical analysis. In one case (Orlynvah), polymorph-related claims were disclosed within the compound patent itself. Among the remaining 12 products, all originator polymorph patents expire later than their corresponding compound patents, with time gaps exceeding one year. Notably, 9 of these products exhibit a gap of three years or more, and 6 show a gap of at least five years. Of particular interest, Sofdra achieved an exceptional 13-year extension of exclusivity through its polymorph patent strategy.

Table 3. Comparative Analysis of Compound and Polymorph Patents for 13 Small Molecule Drugs

Among the 13 products analyzed (including Orlynvah), two representative cases were selected for in-depth discussion to illustrate how innovative pharmaceutical companies leverage polymorph patent strategies to extend product lifecycles. The approval of these two drugs marks a significant milestone, as both exhibit strong therapeutic potential and are anticipated to capture substantial market share.

Voranigo^®

Voranigo^® (vorasidenib), developed by Servier, is approved for the postoperative treatment—including biopsy, subtotal resection, or gross total resection—of grade 2 astrocytoma or oligodendroglioma harboring isocitrate dehydrogenase (IDH) 1 or 2 mutations in patients aged 12 years and older. It is the first and only FDA-approved targeted therapy specifically indicated for IDH-mutant grade 2 gliomas. Voranigo^® exerts its therapeutic effect by selectively inhibiting mutant IDH1/2 enzyme activity, thereby suppressing disease progression in IDH-mutant gliomas. The FDA approval, announced by Servier on August 6, 2024, represents a significant advancement in the treatment landscape for diffuse gliomas.

The active pharmaceutical ingredient in the commercial product is a co-crystal of vorasidenib hemicitrate hemihydrate. The compound patent (US9579324B2) is set to expire on July 11, 2034. In contrast, the polymorph patent (US11345677B2), which discloses the citric acid co-crystal form, extends protection until January 16, 2039. This polymorph patent strategy effectively provides an additional 4.5 years of exclusivity beyond the expiration of the compound patent.

Sofdra^® 

Sofdra^® (sofpironium), developed by Bodor Laboratories Inc., is a topical gel approved for the treatment of primary axillary hyperhidrosis in patients aged 9 years and older. As the first FDA-approved new molecular entity specifically for this indication, Sofdra^® addresses a substantial unmet medical need—hyperhidrosis ranks as the third most prevalent dermatological condition following acne and atopic dermatitis. Existing treatment options range from topical therapies to systemic medications and surgical procedures, each associated with varying degrees of efficacy and adverse effects. As a locally applied anticholinergic agent, Sofdra^® minimizes systemic exposure while achieving meaningful reductions in sweat production and maintaining favorable tolerability in clinical trials. Prior to Sofdra^®, the only FDA-approved topical anticholinergic for hyperhidrosis was glycopyrronium tosylate (Qbrexza), approved in 2018. FDA approval of Sofdra^® was announced by Botanix on June 18, 2024.

The commercial product contains crystalline sofpironium. The compound patent (US8628759B2) is set to expire on November 13, 2026, whereas the polymorph patent (US11584715B2), which discloses multiple crystalline forms (Form A, MN, MJ, CO, and B), extends protection until May 22, 2040. This polymorph patent strategy affords an exceptional 13.5-year extension of market exclusivity beyond the expiration of the compound patent.

Summary

A review of data from the past six years (Table 4) shows that, although the number of approved small-molecule drugs in 2024 declined slightly compared to the previous year, the proportion of solid and semi-solid formulations remained consistent with historical trends. Notably, 60% to 80% of newly approved innovative small-molecule drugs continue to incorporate polymorph patent strategies—underscoring the growing importance of crystal form research in pharmaceutical development.

This trend is driven by two key factors. First, polymorphic properties play a critical role in determining a drug’s bioavailability, stability, and manufacturability—all of which are central to regulatory evaluation and approval. Second, well-constructed polymorph patents serve as effective intellectual property barriers against generic entry, thereby prolonging market exclusivity and enhancing commercial value.

Table 4. Trends in Polymorph Patent Protection Among FDA-Approved New Small Molecule Drugs (2019–2024)

References and Notes

[1] FDA. Novel Drug Approvals 2024. Available at: https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024
[2] Compound patent expiration dates are based on the Orange Book-listed expiration date: https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
[3] For granted patents, expiration dates are determined based on official records published by the relevant authorities.
[4] The expiration gap is calculated as: Polymorph patent expiration date – Compound patent expiration date.