The Food and Drug Administration has cleared an investigational new drug application for AB001, a radioligand therapy that targets prostate-specific membrane antigen with the alpha emitter lead-212. The decision allows the developer to begin a phase 1 clinical trial in men with metastatic castration-resistant prostate cancer.

AB001 has been the subject of preclinical research and an exploratory phase 0 study in Oslo, where three patients received microdoses that were tracked by gamma camera and SPECT imaging. Those data, published earlier this year in the Journal of Nuclear Medicine, showed that the compound localized to metastatic lesions, cleared predictably, and caused no immediate adverse effects at the very low doses used for imaging. While the trial was not intended to measure efficacy, it provided early evidence that AB001 could be administered safely and reach its intended targets.

The upcoming trial in the United States will escalate doses to therapeutic levels and assess safety, tolerability, and preliminary signs of anti-tumor activity. Lead-212 is a short-lived isotope that decays into alpha-emitting daughters, delivering high-energy radiation over a short range. By coupling it to a PSMA-binding molecule, researchers hope to concentrate its effect in prostate cancer cells while limiting exposure to surrounding tissue.

Radioligand therapy is already part of prostate cancer treatment with lutetium-177–based compounds, but alpha emitters such as lead-212 and actinium-225 are being explored for their potentially greater potency. The supply and handling of these isotopes remain a challenge, and clinical experience is limited.

Collaborations have been announced in other regions, including an agreement to develop AB001 in Greater China. Results from the first therapeutic trial will help determine whether the compound can advance to broader testing in men with advanced disease.

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