- The disease
- Metastatic castration-resistant prostate cancer (mCRPC) is prostate cancer that has spread to other parts of the body and continues to grow despite hormone therapies that lower testosterone. It is one of the later and more difficult-to-treat stages of prostate cancer. Patients in this setting have typically already received multiple prior lines of therapy. There remains significant unmet need for treatments that can extend survival or control disease in this population.
- What the asset is trying to do
- Veyonda (idronoxil) is an oral small molecule that targets sphingosine kinase, an enzyme involved in cell survival signalling, and also acts on the STING (stimulator of interferon genes) pathway, which plays a role in immune activation. In the DARRT (DNA-damage And Radiotherapy Response Treatment) program, Veyonda was administered in combination with external beam radiotherapy (EBRT), with the rationale that inhibiting sphingosine kinase could sensitise tumour cells to radiation-induced DNA damage. This combination approach differs from standard hormonal or chemotherapy-based treatments used in mCRPC.
- What the trial is measuring, and why it matters
- The lead mCRPC trial (NCT04957290) was a Phase 1/2 study evaluating NOX66 (a suppository formulation of idronoxil) in combination with EBRT in patients with mCRPC and other solid tumours (per ClinicalTrials.gov NCT04957290). The study's primary completion date was listed as May 2023, and the trial has since been recorded as terminated on ClinicalTrials.gov.
- Efficacy benchmarks in this setting
- In mCRPC, approved therapies have established reference points for survival outcomes. For example, the Phase 3 AFFIRM trial of enzalutamide reported a median overall survival of 18.4 months versus 13.6 months for placebo in post-docetaxel mCRPC patients (per Scher et al, New England Journal of Medicine, 2012). The Phase 3 COU-AA-301 trial of abiraterone acetate plus prednisone reported median overall survival of 14.8 months versus 10.9 months for placebo in a similar post-chemotherapy population (per de Bono et al, New England Journal of Medicine, 2011). The LuPIN study of Veyonda reported a median overall survival figure of 19.7 months (per Noxopharm company disclosure); however, early-phase and single-arm figures are not statistically comparable to randomised controlled trial results for approved agents, and no direct comparison can be drawn.