# 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) As of September 2022, it is in phase 3 clinical trials for androgenic alopecia and phase 2 trials for acne.

## Development

Pyrilutamide has undergone several clinical trials for the treatment of androgenic alopecia (AGA) in both males and females. 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.

### 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:
* 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:
* 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:
* 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:
* 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).
* 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.

### 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.

## Adverse effects

Pyrilutamide is generally well-tolerated. The most common adverse event is contact dermatitis.
Across all trials, KX-826 demonstrated a favorable safety profile:
* 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 IC$_{50}$ of 0.28 nM. Reference drug bicalutamide had an IC$_{50}$ of 3.1 nM.