Wikipedia

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)[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
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
CAS Number
PubChem CID
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

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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

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Male AGA in China

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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

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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.

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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

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Male AGA in China

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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

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  • 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

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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

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

Pharmacodynamics

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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

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  1. ^ "Pyrilutamide".
  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.
  3. ^ a b "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.
  4. ^ 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 
  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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