Pyrilutamide

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)[1] and acne in China and the United States.[2][3] As of October 2022, it is in phase 3 clinical trials for androgenic alopecia and phase 2 trials for acne.[2]

Pyrilutamide
Clinical data
Other namesKX-826
Routes of
administration		Topical
Drug classNonsteroidal antiandrogen
ATC code
  • None
Identifiers
  • 4-(3-(4-cyano-2-fluoro-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide
Chemical and physical data
FormulaC21H15F5N4O2S
Molar mass482.43 g·mol−1
3D model (JSmol)
  • 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=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

Development

Pyrilutamide successfully completed phase II clinical trials in China and is currently in phase II clinical trials in the U.S for the potential treatment of androgenetic alopecia in males. It is currently in phase II clinical trials in China for the potential treatment of androgenetic alopecia in females. The drug was expected to enter phase III clinical trials in Q1 2022 in China and conducted over 24 weeks across more than 20 sites with a sample size of 416.

The primary endpoint is the change from baseline in non-vellus target area hair count (TAHC) at the end of week 24. The drug will be dosed at 10 mg (0.5% BID) per patient per day in the trial.[4]

Adverse effects

Pyrilutamide is generally well-tolerated. The most common adverse event is contact dermatitis.[5]

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. [3] Reference drug bicalutamide had an IC50 of 3.1 nM. [3]

Pharmacokinetics

In Phase I clinical trials, pyrilutamide and metabolite KX-982's systemic absorption was evaluated across different doses of 0.5, 2, 6, 12, and 24 mg/body/day.

References
  1. 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.
  2. "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
  3. 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
  4. "Kintor Pharma Announces the Primary Endpoint of Phase II Clinical Study for KX-826's Treatment of Androgenetic Alopecia Was Met".
  5. "Kintor Pharmaceutical (9939 HK) Specializing in AR-related innovative therapies" (PDF).


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