Setanaxib Shows Promise in Phase 2 Head and Neck Cancer Study

Swedish biopharmaceutical firm Calliditas Therapeutics has reported promising results from a Phase 2 clinical trial of setanaxib, a novel NOX enzyme inhibitor. The study, which combined setanaxib with pembrolizumab, was conducted on patients suffering from squamous cell carcinoma of the head and neck (SCCHN). The findings indicate a significant enhancement in progression-free survival (PFS) and overall survival (OS), along with noticeable shifts in tumor biology that align with setanaxib's proposed mechanism of action.

The trial was structured as a randomized, placebo-controlled, double-blind study, with setanaxib administered at a dosage of 800mg twice daily alongside pembrolizumab, given intravenously at 200mg every three weeks. This regimen is standard for treating SCCHN, and the data set included patients who had completed a minimum of 15 weeks of treatment. The analysis was based on data from 55 patients with recurrent or metastatic SCCHN and tumors with moderate to high levels of CAF-density (Cancer Associated Fibroblasts). Tumor biopsies were performed both before the trial began and after at least nine weeks of treatment.

At the outset, the treatment and control groups were evenly matched with no significant clinical differences. However, the group treated with the combination of pembrolizumab and setanaxib exhibited substantial improvements in PFS, with a median of five months compared to 2.9 months for the placebo group, and a hazard ratio of 0.58. Similarly, improvements in OS were significant, with 92% survival at six months and 88% at nine months for the treatment group, as opposed to 68% and 58% for the placebo group, respectively, with a hazard ratio of 0.45. The disease-control rate also saw an improvement, with 70% of setanaxib-treated patients showing stable disease or better, compared to 52% in the placebo group. Notably, no major differences were observed in the primary endpoint, which was the percentage change in tumor size from the start of the study.

Transcriptomic analysis of the tumor biopsies revealed a significant increase in CD8+ T-cells within the tumor tissue of patients treated with setanaxib, pointing to heightened tumor immunological response. The drug's tolerability was deemed good when combined with pembrolizumab, with no new safety concerns arising.

Kevin Harrington, a professor at The Institute of Cancer Research in London and a consultant at The Royal Marsden NHS Foundation, lauded the study's statistical significance and its implications for advancing setanaxib as a treatment for a challenging disease population. Calliditas' CEO, Renée Aguiar-Lucander, and CMO Richard Philipson, also expressed excitement over the results, which support the company's NOX platform and highlight the drug's potential anti-fibrotic effects.

Calliditas Therapeutics, headquartered in Stockholm, is dedicated to developing innovative treatments for rare diseases with significant medical needs. The company's shares trade on both the Nasdaq Stockholm and the Nasdaq Global Select Market. The positive outcomes of this trial are a step forward in addressing the SCCHN, a disease that affects nearly a million people globally and results in over 400,000 deaths each year. The company is also conducting further trials with setanaxib for other conditions, with results expected throughout the year and into 2025.