Pyrilutamide

Pyrilutamide
Clinical data
Other names	KX-826
Routes of; administration	Topical
Drug class	Nonsteroidal antiandrogen
ATC code	None;
Identifiers
	IUPAC name 4-(3-(4-cyano-2-fluoro-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide;
CAS Number	1272719-00-2;
PubChem CID	50940514;
Chemical and physical data
Formula	C21H15F5N4O2S
Molar mass	482.43 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CNC(=O)C1=C(F)C=C(C=C1)N1C(=S)N(C(=O)C1(C)C)C1=C(F)C(=C(C=C1)C#N)C(F)(F)F;
	InChI InChI=1S/C21H15F5N4O2S/c1-20(2)18(32)29(14-7-4-10(9-27)15(16(14)23)21(24,25)26)19(33)30(20)11-5-6-12(13(22)8-11)17(31)28-3/h4-8H,1-3H3,(H,28,31); Key:CGRMNGGGSWLDDC-UHFFFAOYSA-N;

Pyrilutamide (developmental code name KX-826) is a nonsteroidal antiandrogen (NSAA) – specifically, a selective high-affinity silent antagonist of the androgen receptor (AR) – which is under development by Suzhou Kintor Pharmaceuticals, inc., a subsidiary of Kintor Pharmaceutical Limited, for the potential treatment of androgenic alopecia (androgen-dependent scalp hair loss)^[2]^[3]^[4] As of September 2022, it is in phase 3 clinical trials for androgenic alopecia and phase 2 trials for acne.^[3]

Development

Pyrilutamide has undergone several clinical trials for the treatment of androgenic alopecia (AGA) in both males and females.^[5] The primary endpoint for most trials was the change from baseline in non-vellus target area hair count (TAHC) compared to placebo after 24 weeks of treatment.^[5]

Phase II Trials

Male AGA in China

A phase II trial in China enrolled 120 male patients, randomized into four groups: KX-826 0.25% BID (twice daily), KX-826 0.5% QD (once daily), KX-826 0.5% BID, and placebo. After 24 weeks, the 0.5% BID group showed significant improvement:^[5]

Non-vellus target area hair count (TAHC) increased by 22.73 hair counts per cm² from baseline (P<0.001)
TAHC increased by 15.34 hair counts per cm² compared to placebo (P=0.024)

Female AGA in China

A phase II trial for female AGA in China included 160 patients in five groups: KX-826 0.25% QD, 0.25% BID, 0.5% QD, 0.5% BID, and placebo. After 24 weeks:^[5]

The 0.5% QD group showed an increase of 11.39 hair counts per cm² compared to placebo (P=0.0087)
Efficacy was observed as early as 12 weeks

Male AGA in the U.S.

A phase II trial in the U.S. enrolled 123 male patients, divided into KX-826 0.25% QD, 0.5% QD, 0.5% BID, and placebo groups. Results after 24 weeks showed:^[5]

The 0.5% BID group increased by approximately 10 hair counts per cm² from baseline (P=0.0088)
A dose-response relationship was observed across different dosage groups

Phase III Trials

Male AGA in China

A phase III trial for male AGA in China enrolled 740 patients, randomized into KX-826 0.5% BID and placebo groups. Results announced on November 27, 2023, showed:^[5]

KX-826 promoted hair growth compared to baseline with statistical significance (P<0.0001)
Improvement in TAHC at all visit points compared to placebo, though without statistical significance

Ongoing Studies

A long-term safety phase III trial for AGA treatment in China, enrolling 271 male and female patients for a 52-week treatment period, focusing on treatment-emerged adverse events (TEAE).^[5]
A phase Ib/III clinical trial of KX-826 in combination with minoxidil for male AGA in China, approved by NMPA on February 1, 2024.^[5]

Adverse effects

Pyrilutamide is generally well-tolerated. The most common adverse event is contact dermatitis.^[6]

Across all trials, KX-826 demonstrated a favorable safety profile:^[5]

No serious adverse events (SAE) or adverse drug reactions (ADR) were reported
Most treatment-emerged adverse events (TEAE) were mild and similar to placebo
Low systemic exposure was observed after topical application

Pharmacology

Plasma concentration of pyrilutamide and metabolite KX-982 in different dose groups in phase Ib clinical trials in China

Pharmacodynamics

Pyrilutamide binds to the androgen receptor with a very high affinity with an IC₅₀ of 0.28 nM.^[4] Reference drug bicalutamide had an IC₅₀ of 3.1 nM.^[4]

References

^ "Pyrilutamide".
^ Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S, Grimalt R (January 2023). "What's New in Therapy for Male Androgenetic Alopecia?". American Journal of Clinical Dermatology. 24 (1): 15–24. doi:10.1007/s40257-022-00730-y. PMID 36169916.
^ ^a ^b "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
^ ^a ^b ^c CA patent 2829322, Tong Y, "Substituted Thioimidazolidinone Androgen Receptor Antagonists and Uses Thereof", published 2012-03-08, issued 2017-01-10, assigned to Suzhou Kintor Pharmaceuticals, Inc
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ "Annual Results Announcement for the Year Ended 31 December 2023" (PDF). Kintor Pharmaceutical Limited. March 28, 2024. Retrieved 2024-09-12.
^ "Kintor Pharmaceutical (9939 HK) Specializing in AR-related innovative therapies" (PDF).

[1] "Pyrilutamide".

[pmid36169916-2] Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S, Grimalt R (January 2023). "What's New in Therapy for Male Androgenetic Alopecia?". American Journal of Clinical Dermatology. 24 (1): 15–24. doi:10.1007/s40257-022-00730-y. PMID 36169916.

[AdisInsight-3] "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.

[Patent-4] CA patent 2829322, Tong Y, "Substituted Thioimidazolidinone Androgen Receptor Antagonists and Uses Thereof", published 2012-03-08, issued 2017-01-10, assigned to Suzhou Kintor Pharmaceuticals, Inc

[KintorAnnual2023-5] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ "Annual Results Announcement for the Year Ended 31 December 2023" (PDF). Kintor Pharmaceutical Limited. March 28, 2024. Retrieved 2024-09-12.

[6] "Kintor Pharmaceutical (9939 HK) Specializing in AR-related innovative therapies" (PDF).

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