FDA Clears Phase 2b Trial of Teverelix in Advanced Prostate Cancer Patients at High Cardiovascular Risk

A new phase 2b clinical trial has received FDA “study may proceed” clearance for teverelix, a long‑acting GnRH antagonist being evaluated in men with advanced prostate cancer who are at high cardiovascular risk.The trial is designed to test a dose‑optimization regimen of teverelix over a 22‑week treatment period, with the primary goal of confirming medical castration by day 29 and sustaining testosterone suppression through day 155 at a probability exceeding 90%. The study will enroll approximately 40 androgen‑deprivation therapy–eligible men whose coronary artery calcium score exceeds 400 and who have elevated atherosclerotic cardiovascular disease risk, including those with recent major adverse cardiovascular events or severe subclinical atherosclerosis.

Teverelix is formulated as a long‑acting, microcrystalline suspension for intramuscular and subcutaneous administration and acts as a GnRH receptor antagonist, providing immediate blockade of gonadotropin release and suppressing luteinizing hormone and follicle‑stimulating hormone without the testosterone surge typically seen with traditional GnRH agonists. In this phase 2b plan, the proposed regimen includes an initial loading phase of 180 mg intramuscular injection on day 0 plus two 180 mg subcutaneous doses later in the first cycle, for a total of 540 mg, followed by maintenance dosing of two 180 mg subcutaneous injections on day 29 and then every six weeks thereafter through week 22.

The trial builds on prior work with an earlier version of the same GnRH antagonist, which was evaluated in a phase 2 study (TEACh) in men with advanced adenocarcinoma of the prostate who were naive to GnRH analogues, androgen‑receptor antagonists, and androgen‑synthesis inhibitors. In that earlier trial, patients received varying intramuscular and subcutaneous loading doses—120 mg or 180 mg—followed by 4‑ to 6‑week maintenance cycles up to 24 weeks, with primary endpoints focused on castration at four weeks, time to castrate testosterone levels, and sustained LH and FSH suppression. Analyses of that program indicated the compound was generally well tolerated but the original dosing and formulation did not consistently maintain adequate castration, prompting reformulation and refinement into the current teverelix regimen.

A key driver of this new trial is the recognition that cardiovascular disease accounts for roughly 30% of deaths in men with prostate cancer and that androgen‑deprivation therapy can exacerbate pre‑existing cardiovascular risk. Observational data suggest that men with high cardiovascular risk treated with GnRH agonists may experience a 5–6‑fold higher incidence of major adverse cardiovascular events compared with those receiving GnRH antagonists, particularly in patients with prior heart disease or severe atherosclerosis. The current phase 2b trial explicitly targets this subgroup, using objective measures such as coronary artery calcium scoring and ASCVD risk calculations to define eligibility and aims to preserve the hormone‑suppressive potency of ADT while minimizing cardiovascular harm.

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