Chemistry: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][2][3] As of September 2022, it is in phase 3 clinical trials for androgenic alopecia and phase 2 trials for acne.[2]
Development
Pyrilutamide has undergone several clinical trials for the treatment of androgenic alopecia (AGA) in both males and females.[4] 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.[4]
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:[4]
- 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:[4]
- 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:[4]
- 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:[4]
- 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).[4]
- 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.[4]
Availability as a Cosmetic Product
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.[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:[4]
- 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
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]
See also
- List of investigational acne drugs
- List of investigational hair loss drugs
- GT-20029 (AR-PROTAC)
- Clascoterone (Winlevi; Breezula; CB-03-01)
References
- ↑ "What's New in Therapy for Male Androgenetic Alopecia?". American Journal of Clinical Dermatology 24 (1): 15–24. January 2023. doi:10.1007/s40257-022-00730-y. PMID 36169916.
- ↑ 2.0 2.1 "Pyrilutamide - Suzhou Kintor Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800053879.
- ↑ 3.0 3.1 3.2 Tong Y, "Substituted Thioimidazolidinone Androgen Receptor Antagonists and Uses Thereof", CA patent 2829322, published 2012-03-08, issued 2017-01-10, assigned to Suzhou Kintor Pharmaceuticals, Inc
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 "Annual Results Announcement for the Year Ended 31 December 2023" (PDF). Kintor Pharmaceutical Limited. March 28, 2024. https://www1.hkexnews.hk/listedco/listconews/sehk/2024/0328/2024032802816.pdf.
- ↑ "KX-826 (Pyrilutamid): Neue Hoffnung im Kampf gegen Haarausfall - HealthHeld" (in de). 2024-10-29. https://healthheld.de/haarausfall/kx-826.
- ↑ "Kintor Pharmaceutical (9939 HK) Specializing in AR-related innovative therapies". http://pdf.dfcfw.com/pdf/H3_AP202007241393752560_1.pdf.
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