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[1]
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]

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]

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)

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

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

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

• 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]

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

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]