Pyrilutamide for Hair Loss Treatment: What We Know So Far

Pyrilutamide (developmental code name KX-826) is a topical androgen receptor (AR) antagonist currently being developed as a potential topical treatment for androgenetic alopecia.

The drug innovator is  Kintor Pharmaceutical Limited, which is known for developing and commercializing innovative treatments for AR-related diseases with unmet medical needs like androgenic alopecia, acne vulgaris, and breast and prostate cancer. Its accessibility is nearing since completed, and ongoing clinical trials to further prove its efficacy and safety exist, which would eventually lead to FDA approval.

Clinical trials of pyrilutamide for hair loss treatment

Phase I/ Ib clinical trials

A recently completed phase I clinical trial done in the US was a randomized, double-blind, placebo-controlled, parallel-group, and dose-escalation study. Subjects are 40 healthy male patients, 18 to 60 years old, with androgenetic alopecia.

This clinical study was done to evaluate the safety, tolerability, and pharmacokinetics of the topical AR antagonist, Pyrilutamide, following multiple ascending dose administrations of 3mg, 12mg, 48mg, and 96mg.

The pharmacokinetic study showed that blood concentrations of pyrilutamide among the subjects remained extremely low throughout the study. In terms of safety, there were no associated severe adverse drug events.

Phase II clinical trials

Several clinical trials were done in China and in the US. In 2020, the first phase II clinical trial was a multiregional randomized placebo-controlled study done in China.

In this study, 120 subjects with male androgenetic alopecia were included and randomized into four dose groups: 2.5 mg (0.25%) pyrilutamide twice a day, 5.0 mg (0.5%) once a day, 5.0 mg (0.5%) twice a day and the placebo (2,5,6). The main result of this study was the change in non-vellus target area hair count (TAHC) from the baseline and after six months of treatment.

Professor Jianzhong Zhang presented results showed that among all the subjects, those on pyrilutamie 0.5% applied twice a day exhibited statistically significant improvement in total area hair count after six months of treatment, with 22.73 hairs per cm2 increase, as opposed to the placebo group with only 15.34 hairs per cm2 increase. Because of these results, 0.5% pyrilutamide solution was used in phase III clinical trial.

In December 2022, the results of another phase II clinical study about the use of pyrilutamide were published, but this time, on the treatment of female pattern hair loss (female AGA).

In total 41 participants were assigned to the placebo group and 119 subjects with female AGA were randomly assigned to four treatment groups with varying doses of KX-826:

Results showed that the pyrilutamide 0.5% solution applied once a day significantly increased hair count by 11.39 per cm2 from baseline after 24 weeks of treatment. Improvement in hair density was seen as early by the end of week 12. Like the previous phase II trials, KX-826 exhibited a good safety profile.

Phase III clinical trial

In November 2021, the Phase III clinical trial protocol for KX-826 to treat male androgenetic alopecia was greenlighted. The randomized, double-blind, placebo-controlled, multi-regional phase III clinical trial is being done in the top 26 dermatology institutions in China, headed by Peking University People’s Hospital and Huashan Hospital. The leading principal investigators were Professor Zhang Jianzhong and Professor Yang Qinping (8).  

In June 2022, 416 male patients were enrolled in this study. This study was designed to evaluate the efficacy and safety profile of KX-826 for male pattern hair loss. The trial duration is also 24 weeks with a 4-week follow-up. The primary endpoint is also the change in non-vellus TAHC from baseline at the end of week 24.

Payrilutamide’s mechanism of action

Being an AR antagonist, Pyrilutamide (KX-826) prevents androgens from binding to its receptors in the hair follicles by binding to them instead. This prevents the effects of androgens, like miniaturization and eventual hair loss.

Thus, unlike the 5-alpha reductase inhibitors like topical finasteride, it cannot decrease systemic androgen levels. Thus, even with prolonged treatment, KX-826 is unlikely to cause unwanted adverse drug events commonly seen in patients with 5 alpha-reductase inhibitors.

Pyrilutamide (KX-826) can potentially redefine the market for androgenetic alopecia drugs. Effective treatments that can improve hair thickness and hair growth among patients with androgenic alopecia are limited. These include surgical hair transplants and hair cloning, which are inaccessible to some.

Currently, there are only two FDA-approved drugs for male androgenetic alopecia, topical minoxidil, and finasteride 1 mg tablet, and only one for female AGA, which is topical minoxidil.

Each drug has its limitations. For minoxidil, the mechanism of action is not well-established, and patients’ treatment response is limited, though it has a good safety profile.

Though they cause a significant improvement in treating hair loss, some anti-androgens like finasteride are associated with bothersome side effects like decreased libido, erectile dysfunction, and depression, which may persist even upon treatment discontinuation.

How to dose pyrilutamide?

Based on the clinical trials, Pyrilutamide 0.5%  applied once a day for female AGA and twice a day for male AGA exhibited the highest treatment efficacy.

Side effects of pyrilutamide

Based on the completed clinical trials, adverse drug events were mild and limited to mild contact dermatitis, which was mainly due to the excipients and not the drug itself. The contact dermatitis improved easily and lasted briefly.

Availability of pyrilutamide

At this moment pyrilutamide 0.5% solution with propylene glycol and ethanol vehicle can be purchased online for research purposes.

Conclusion

Pyrilutamide is a novel topical drug that can potentially be a first-class drug for both female and male pattern hair loss. Because of its efficacy and good safety profile, based on the completed clinical trials, this Kintor drug is a good addendum to the two existing FDA-approved drugs for androgenetic alopecia.