Pyrilutamide
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| Clinical data | |
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| Other names | KX-826 |
| Routes of administration | Topical |
| Drug class | Nonsteroidal antiandrogen |
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| Chemical and physical data | |
| Formula | C21H15F5N4O2S |
| Molar mass | 482.43 g·mol−1 |
| 3D model (JSmol) | |
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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
[edit]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
[edit]Male AGA in China
[edit]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
[edit]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.
[edit]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
[edit]Male AGA in China
[edit]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
[edit]- 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]
Availability as a Cosmetic Product
[edit]In addition to its ongoing clinical development, Pyrilutamide has been introduced to the market as a cosmetic anti-hair loss product under the brand name Koshine. This approach allows it to be made available to consumers without the need for full regulatory approval as a medical treatment. Its classification as a cosmetic reflects a strategic decision to facilitate earlier access while formal medical approval is still pending.[6]
Adverse effects
[edit]Pyrilutamide is generally well-tolerated. The most common adverse event is contact dermatitis.[7]
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
[edit]
Pharmacodynamics
[edit]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
[edit]- ^ "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.
- ^ "KX-826 (Pyrilutamid): Neue Hoffnung im Kampf gegen Haarausfall - HealthHeld" (in German). 2024-10-29. Retrieved 2024-12-05.
- ^ "Kintor Pharmaceutical (9939 HK) Specializing in AR-related innovative therapies" (PDF).