Phase 1 Trial: HSK46575 a Novel CYP11A1 Inhibitor for mCRPC

A new drug, HSK46575, is being tested for metastatic castration-resistant prostate cancer (mCRPC). This small molecule inhibitor, now in early clinical trials in China, targets a specific enzyme to slow cancer progression.
HSK46575 focuses on CYP11A1, an enzyme that starts the production of steroid hormones, including androgens like testosterone, which can drive prostate cancer growth. By blocking this enzyme, the drug aims to reduce these hormones and limit tumor growth. Lab studies showed it reduced tumor size and prostate-specific antigen (PSA) levels, a marker of cancer activity, in models of CRPC.
The drug is taken orally once daily, which may be more convenient than some treatments requiring multiple doses.

In animal studies, HSK46575 effectively reduced hormone levels and slowed prostate cancer growth. In rats, it worked in a dose-dependent, long-lasting way. In mice with specific prostate cancer models, a low dose of 1 mg/kg/day reduced tumor growth and PSA levels, a marker of cancer activity. At 2.5 mg/kg/day, it outperformed higher doses of another drug, abiraterone, and matched the effectiveness of ODM-208. HSK46575 was well-absorbed, stayed in the body longer, and cleared out more slowly, supporting once-daily dosing compared to ODM-208’s twice-daily schedule. It was also well-tolerated  and showed a good safety profile.

Compared to existing treatments like abiraterone or enzalutamide, HSK46575 targets an earlier step in hormone production, which may help in cases where resistance develops.

Clinical trial.

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