First-in-Class Topical GT20029 Demonstrates Promising Phase 2 Efficacy and Tolerability for AGA

Early clinical findings demonstrated acceptable safety and systemic exposure profiles of GT20029, a first-in-class, topical AR proteolysis-targeting chimera (PROTAC) for the treatment of androgenetic alopecia (AGA).¹ After 12 weeks of treatment, 4 tested doses of the drug produced statistically significant improvements from baseline.

Background

The incidence and prevalence of AGA are well established but truly effective and safe treatment options are currently unavailable. Although topical minoxidil and oral finasteride remain the only FDA-approved pharmacologic therapies for AGA, both have limitations related to efficacy, tolerability, and adherence. As a result, there remains a substantial unmet clinical need for safe, well-tolerated treatments that directly target the molecular pathophysiology of AR signaling within the scalp.

GT20029, rather than blocking AR binding or inhibiting androgen synthesis, induces degradation of AR protein rather than inhibiting ligand binding or androgen synthesis. Phase 1 safety, tolerability, and pharmacokinetics trials were completed in December 2024.²

Methods & Materials

The multicenter, randomized, double-blind, placebo-controlled phase 2 trial investigated topical GT20029 in adult Chinese male patients with mild-to-moderate AGA (Hamilton-Norwood IIIv–V). A total of 180 participants were enrolled across 12 sites and randomized equally to 6 treatment arms: GT20029 0.5% or 1.0% applied once daily (QD), GT20029 0.5% or 1.0% applied twice weekly (BIW), or matched placebo regimens. All patients applied the assigned solution to the affected area for 12 weeks, followed by a 28-day off-treatment follow-up.

The primary endpoint was the mean change from baseline in target area non-vellus hair count (TAHC) at week 12, assessed via standardized macrophotography using the FotoFinder system. Secondary endpoints included TAHC at week 6, target area hair width (TAHW), terminal-to-vellus hair ratio, and subgroup analyses stratified by baseline severity and demographic variables. Safety profile and adverse events were evaluated through laboratory testing, vital signs, ECGs, and local scalp assessments. Pharmacokinetic sampling was conducted in approximately one-third of participants.

Efficacy Results

All 4 GT20029 treatment groups demonstrated statistically significant within-group increases in TAHC at week 12. Between-group comparisons showed that GT20029 0.5% QD (LSM +16.80 hairs/cm² vs +10.10 placebo; p = 0.032) and GT20029 1.0% BIW (+11.94 vs +4.57 hairs/cm²; p = 0.023) achieved significant improvements relative to their respective placebo controls.

Although no clear dose-response trend emerged in QD groups, BIW regimens demonstrated increasing efficacy with higher concentrations. Subgroup analyses suggested that participants with moderate baseline severity (Hamilton-Norwood IV), higher baseline TAHC, younger age, higher BMI, or no prior AGA treatment may derive particular benefit from GT20029, especially at the 1.0% BIW dose.

Secondary efficacy outcomes corroborated these findings. By week 6, the 1.0% BIW group had significantly greater TAHC improvement compared with placebo (p = 0.030), indicating an early treatment effect. All active groups demonstrated numerical increases in TAHW, with the 1.0% BIW arm achieving a statistically significant benefit over placebo at week 12 (0.54 vs −0.02 mm/cm²; p = 0.011). Improvements in hair width and non-vellus hair counts also aligned.

Safety and Pharmacokinetics

Pharmacokinetic results showed low and variable systemic exposure across all regimens, with no evidence of dose-proportional accumulation and no clinically meaningful changes in serum testosterone. This low systemic absorption is consistent with the topical mechanism of GT20029 and supports its favorable risk profile.

Regarding safety, GT20029 was generally well tolerated. Rates of treatment-emergent adverse events were similar between active and placebo groups, and most reactions were mild and localized. Application-site pruritus was the most common adverse effect (7.3% of active-treated subjects). No drug-related serious adverse events occurred, and no patients in the GT20029 groups discontinued. Systemic safety parameters—including hematology, chemistry, urinalysis, and ECGs—remained stable throughout the trial.

Conclusion

This phase 2 study provides the first controlled evidence that topical GT20029 produces clinically meaningful improvements in hair density and hair shaft caliber in men with AGA, with favorable tolerability and minimal systemic exposure. While the study’s relatively short duration and modest sample size warrant cautious interpretation, the results support continued development of GT20029. Phase 3 trials assessing longer-term outcomes, optimal dosing schedules, and comparisons or combinations with existing therapies are now underway.

References

1. Hu R, Wei A, Wu L, et al. Efficacy and safety of topical GT20029 in male patients with androgenetic alopecia: a multicenter, randomized, double-blind, placebo-controlled phase 2 study. J Dermatolog Treat. 2025;36(1):2574304. doi:10.1080/09546634.2025.2574304

2. Huang T, Dong M, Dubois J, et al. Ni X safety, tolerability and pharmacokinetics (PK) of GT20029 following topical single ascending dose (SAD) administration in healthy volunteers and multiple ascending dose (MAD) administration in subjects with Androgenetic Alopecia (AGA) or acne. Presented at European Academy of Dermatology and Venereology (EADV); Berlin, Germany; October 11-14, 2023. Abstract: 3798.