Crystal Pharmatech Viewpoint: Analysis of Crystal Form Patent Layouts for Small Molecule New Drugs Approved by the FDA in 2025

1. Overview of FDA New Drug Approvals in 2025

In 2025, the U.S. Food and Drug Administration (FDA) approved a total of 46 new drugs ^[1], including 34 new molecular entities (NMEs). Among these, 30 are small molecule drugs.

Regarding administration routes and dosage forms for these 30 small molecule drugs,

· Three are liquid formulations (including two ophthalmic solutions and one nasal spray)

· 27 products are solid or semi-solid formulations (including one lyophilized powder for injection and one cream)

The basic information is detailed in Table 1.

Table 1. Basic Information of 34 New Molecular Entities Approved by the FDA in 2025

No.	Drug Name	Active Ingredient	Originator	Indication	Target	Type	Dosage Form
1	Grafapex	treosulfan	Medexus Pharma	Allogeneic hematopoietic stem cell transplantation	Adds alkyl groups to DNA structure to kill cells	Small Molecule	Lyophilized powder for injection
2	Journavx	suzetrigine	Vertex Pharmaceuticals	Moderate-to-severe acute pain in adults	NaV1.8 pain signal inhibitor	Small Molecule	Tablet
3	Gomekli	mirdametinib	SpringWorks Therapeutics	Neurofibromatosis type 1 (NF1)	MEK inhibitor	Small Molecule	Capsule, tablet for oral suspension
4	Romvimza	vimseltinib	Deciphera Pharmaceuticals	Symptomatic tenosynovial giant cell tumor	CSF1R inhibitor	Small Molecule	Capsule
5	Blujepa	gepotidacin	GSK	Uncomplicated urinary tract infection in females ≥12 yrs, weight ≥40kg	Triazaacenaphthylene antibiotic (blocks DNA replication/transcription)	Small Molecule	Tablet
6	Qfitlia	fitusiran	Sanofi/Alnylam	Prevention/reduction of bleeding in Hemophilia A or B	RNAi targeting AT mRNA to lower plasma AT and promote coagulation	siRNA	Injection
7	Vanrafia	atrasentan	Novartis	Reduction of proteinuria in adults with primary IgAN at risk of rapid progression	Endothelin A (ETA) receptor antagonist	Small Molecule	Tablet
8	Avmapki Fakzynja Co-Pack	avutometinib and defactinib	Verastem	Recurrent low-grade serous ovarian cancer (LGSOC) with KRAS mutation	Dual action inhibition of signal transduction pathways	Combination	Capsule/ Tablet
9	Tryptyr	acoltremon	Alcon	Dry Eye Disease (DED)	TRPM8 selective agonist	Small Molecule	Eye drops
10	Ibtrozi	taletrectinib	Nuvation Bio	ROS1-positive non-small cell lung cancer (NSCLC)	ROS1 inhibitor	Small Molecule	Capsule
11	Zegfrovy	sunvozertinib	Dizal	NSCLC with EGFR exon 20 insertion mutations	EGFR exon20ins	Small Molecule	Tablet
12	Ekterly	sebetralstat	KalVista	Acute HAE attacks in adults and pediatric patients ≥12 yrs	Plasma kallikrein inhibitor	Small Molecule	Tablet
13	Anzupgo	delgocitinib	LEO Pharma	Moderate-to-severe chronic hand eczema	Pan-JAK inhibitor	Small Molecule	Cream
14	Sephience	sepiapterin	PTC Therapeutics	Phenylketonuria (PKU) in children and adults	Increases PAH activity, lowers blood phenylalanine	Small Molecule	Powder
15	Vizz	aceclidine	LENZ Therapeutics	Presbyopia in adults	Muscarinic agonist	Small Molecule	Eye drops
16	Modeyso	dordaviprone	Jazz Pharmaceuticals	Recurrent H3 K27M-mutant diffuse midline glioma	ClpP protease activator; Dopamine D2 receptor inhibitor	Small Molecule	Capsule
17	Hernexeos	zongertinib	BI	HER2-mutant non-squamous NSCLC	HER2	Small Molecule	Tablet
18	Brinsupri	brensocatib	Insmed Incorporated	Non-cystic fibrosis bronchiectasis (NCFB)	Dipeptidyl peptidase 1 (DPP1) inhibitor	Small Molecule	Tablet
19	Dawnzera	donidalorsen	Ionis	Prophylaxis of Hereditary Angioedema (HAE) attacks	RNAi targeting PKK to reduce plasma kallikrein	Antisense	Injection
20	Wayrilz	rilzabrutinib	Sanofi	Chronic ITP in adults with inadequate response to prior therapy	BTK inhibitor	Small Molecule	Tablet
21	Forzinity	elamipretide	Stealth BioTherapeutics	Barth Syndrome	Targets inner mitochondrial membrane to improve function	Peptide	Injection
22	Inluriyo	imlunestrant	Eli Lilly	ER+/HER2- advanced or metastatic breast cancer with ESR1 mutations	Estrogen Receptor (ER) antagonist	Small Molecule	Tablet
23	Palsonify	paltusotine	Crinetics	Acromegaly in adults ineligible for/unresponsive to surgery	SSTR2 agonist	Small Molecule	Tablet
24	Rhapsido	remibrutinib	Novartis	Chronic spontaneous urticaria (CSU) in adults	BTK inhibitor	Small Molecule	Tablet
25	Jascayd	nerandomilast	BI	Idiopathic pulmonary fibrosis (IPF)	PDE4B inhibitor	Small Molecule	Tablet
26	Lynkuet	elinzanetant	Bayer	Moderate-to-severe hot flashes associated with menopause	NK-1 and NK-3 receptor antagonist	Small Molecule	Capsule
27	Kygevvi	doxecitine and doxribtimine	UCB	TK2 deficiency in adults and pediatric patients	Restores mitochondrial DNA copy number	Fixed-dose Combo	Powder
28	Komzifti	ziftomenib	Kura Oncology	Relapsed/Refractory AML with NPM1 mutation	Menin inhibitor	Small Molecule	Capsule
29	Redemplo	plozasiran	Arrowhead	Familial Chylomicronemia Syndrome (FCS)	RNAi degrading apoC-III mRNA	siRNA	Injection
30	Hyrnuo	sevabertinib	Bayer	HER2 (ERBB2) TKD mutant NSCLC	TKI inhibitor	Small Molecule	Tablet
31	Nuzolvence	zoliflodacin	Innoviva Specialty	Uncomplicated urogenital gonorrhea	Type II topoisomerase inhibitor	Small Molecule	Granules
32	Cardamyst	etripamil	Milestone Pharmaceuticals	Paroxysmal supraventricular tachycardia (PSVT)	Calcium channel blocker	Small Molecule	Nasal spray
33	Myqorzo	aficamten	Cytokinetics	Obstructive hypertrophic cardiomyopathy (oHCM)	Selective cardiac myosin inhibitor	Small Molecule	Tablet
34	Nereus	tradipitant	Vanda Pharmaceuticals	Prevention of nausea from motion sickness	Neurokinin-1 receptor antagonist	Small Molecule	Capsule

2. Analysis of Crystal Form Patent Layouts for Solid/Semi-Solid Drugs

An analysis of patent strategies for the 27 solid or semi-solid small molecule drugs revealed that 22 products have already established crystal form patent layouts (including patents under examination). This represents 81.5% of all solid/semi-solid small molecule drugs approved in 2025, indicating that crystal form patent protection has become a mainstream strategy among originator companies.

Table 2. Crystal Form Patent Layout for 27 Solid/Semi-Solid Small Molecule Drugs

No.	Drug Name	Active Ingredient	Originator	Crystal Form Patent Status
1	Grafapex	treosulfan	Medexus Pharma	Disclosed
2	Journavx	suzetrigine	Vertex	Disclosed in compound patent
3	Gomekli	mirdametinib	SpringWorks	Disclosed in compound patent
4	Romvimza	vimseltinib	Deciphera	Not granted
5	Blujepa	gepotidacin	GSK	Not granted
6	Vanrafia	atrasentan	Novartis	Expired
7	Avmapki Fakzynja Co-Pack	avutometinib/defactinib	Verastem	Granted
8	Ibtrozi	taletrectinib	Nuvation Bio	Not granted
9	Zegfrovy	sunvozertinib	Dizal	Not granted
10	Ekterly	sebetralstat	KalVista	Granted
11	Anzupgo	delgocitinib	LEO Pharma	Granted
12	Sephience	sepiapterin	PTC Therapeutics	Granted
13	Modeyso	dordaviprone	Jazz	Not granted
14	Hernexeos	zongertinib	BI	Not granted
15	Brinsupri	brensocatib	Insmed	Disclosed in compound patent
16	Wayrilz	rilzabrutinib	Sanofi	Not found
17	Inluriyo	imlunestrant	Eli Lilly	Granted
18	Palsonify	paltusotine	Crinetics	Granted
19	Rhapsido	remibrutinib	Novartis	Not granted
20	Jascayd	nerandomilast	BI	Disclosed in compound patent
21	Lynkuet	elinzanetant	Bayer	Granted
22	Kygevvi	doxecitine/doxribtimine	UCB	Granted
23	Komzifti	ziftomenib	Kura Oncology	Not granted
24	Hyrnuo	sevabertinib	Bayer	Not found
25	Nuzolvence	zoliflodacin	Innoviva	Not found
26	Myqorzo	aficamten	Cytokinetics	Not granted
27	Nereus	tradipitant	Vanda	Granted

3. Comparison of Compound and Crystal Form Patent Expiration

For the 22 products with crystal form patent layouts, we analyzed the expiration dates. Excluding nine products still under examination:

· Five products (Journavx, Gomekli, Brinsupri, Inluriyo, and Jascayd) disclosed crystal form information within their compound patents.

· Eight products have crystal form patents expiring later than the corresponding compound patents. Among these, four products show a protection extension of three years or more, and two products have an extension of five years or more.

Table 3. Patent Analysis of 13 Small Molecule New Drugs

No.	Drug Name	Compound Patent	Compound Expiry	Crystal Patent	Crystal Expiry	Difference (Years)	Notes
1	Journavx	US11834441B2	2040-12-04	US11834441B2	2040-12-04	NA	Disclosed in compound patent
2	Gomekli	US7411001B2	2022-02-17	US7411001B2	2022-02-17	NA	Disclosed in compound patent
3	Avmapki Fakzynja	US7897792B2	2027-02-09	US11873296B2	2042-12-29	~15.9	-
4	Ekterly	US10364238B2	2035-11-26	US11230537B2	2037-12-25	~2.1	-
5	Anzupgo	US8609647B2	2031-09-19	US11339181B2	2037-12-20	~6.3	-
6	Sephience	Not found	Not found	US11072614B2	2038-04-16	NA	Possible no compound patent
7	Brinsupri	US9522894B2	2035-03-12	US9522894B2	2035-03-12	NA	Disclosed in compound patent
8	Inluriyo	US10654866B2	2039-07-11	US10654866B2	2039-07-11	NA	Disclosed in compound patent
9	Palsonify	US10597377B2	2037-07-12	US10464918B2	2039-01-16	~1.5	-
10	Jascayd	US8609670B2	2032-08-23	US8609670B2	2032-08-23	NA	Disclosed in compound patent
11	Lynkuet	US7683056B2	2026-09-15	US8796269B2	2030-10-03	~4.1	-
12	Kygevvi	US10471087B2	2036-08-07	US11649259B2	2040-08-19	~4.0	-
13	Nereus	US7320994B2	2024-06-06	US7381826B2	2025-02-11	~0.7	-

4. Case Studies

We selected 2 representative products to illustrate how innovators use crystal form patents to extend product lifecycles.

4.1 Gomekli (Mirdametinib)

GOMEKLI™ (Mirdametinib), developed by SpringWorks Therapeutics, is approved for the treatment of adults and pediatric patients aged two years and older with neurofibromatosis type 1–associated plexiform neurofibromas (NF1-PN). Mirdametinib is a mitogen-activated protein kinase (MAP2K/MEK/MAPKK) inhibitor that suppresses MEK1 and MEK2 kinase activity and downstream ERK phosphorylation. The drug was approved by the FDA on February 11, 2025.

The compound patent for Mirdametinib (US7411001B2) expired on February 17, 2022, and disclosed two crystal forms (Form I and Form II). Subsequent crystal form patents (US11066358B1 and US11084780B1) disclosed additional crystal forms and extend protection until February 17, 2041. Although these patents significantly extend the protection period, the early disclosure of crystal forms in the compound patent may leave certain opportunities for generic development.

4.2 Sephience (Sepiapterin)

SEPHIENCE™ (Sepiapterin), developed by PTC Therapeutics, is an oral powder formulation indicated for adult and pediatric patients aged one month and older with hyperphenylalaninemia (HPA) who are responsive to Sepiapterin therapy. It is the first oral therapy for phenylketonuria (PKU) that works by activating the tetrahydrobiopterin (BH4) pathway. FDA approval was granted on July 28, 2025.

Based on available patent information, Sepiapterin is presumed to have no compound patent. Its crystal form patent (US11072614B2) protects multiple free-base crystal forms (Forms A–G) and various salt forms, with an expiration date of April 16, 2038. This crystal form patent strategy provides nearly 13 years of post-approval market protection.

5. Summary and Industry Implications

A review of FDA approval data from the past six years (Table 4) shows that the proportion of small molecule drugs with crystal form patent layouts has remained consistently high, ranging from 60% to 85%. Crystal form patents play a dual role in innovative drug development. First, they serve as a critical life-cycle management tool by extending market exclusivity beyond compound patent expiration. Second, specific crystal forms are often closely associated with key product attributes such as stability, bioavailability, and manufacturability, thereby creating substantial technical and regulatory barriers to generic entry.

Overall, systematic crystal form research and strategic patent layout are essential not only for maximizing intellectual property value and commercial returns, but also for driving technological optimization and ensuring long-term product competitiveness.

Year	2020	2021	2022	2023	2024	2025
FDA Approved New Drugs	53	50	37	55	50	46
Small Molecule Drugs	34	31	17	38	28	30
Solid/Semi-Solid	20	23	15	24	22	27
Originator Crystal Patent	12	16	10	20	15	22
% with Crystal Patent	60%	70%	67%	83%	68%	81.50%