Calliditas sees survival gains in setanaxib trial

Calliditas Therapeutics has unveiled top-line results from a Phase II trial assessing setanaxib in patients with squamous cell carcinoma of the head and neck (SCCHN). The primary objective of significantly reducing tumor size was not met, but the NOX inhibitor showed notable improvements in key secondary endpoints, including progression-free survival (PFS) and overall survival (OS).

The randomized study focused on the efficacy of setanaxib administered twice daily alongside Merck & Co.'s PD-1 inhibitor Keytruda (pembrolizumab), a customary treatment for SCCHN. The trial included 55 patients with recurrent or metastatic SCCHN characterized by moderate or high levels of cancer-associated fibroblasts (CAFs).

Despite the primary endpoint miss, the secondary outcomes were promising. The median progression-free survival for the setanaxib group was 5 months, compared to 2.9 months for the control group receiving Keytruda plus placebo. Additionally, the overall survival rate at six months was 92% for patients treated with setanaxib, significantly higher than the 68% observed in the comparator group. By nine months, these figures stood at 88% and 58%, respectively.

Kevin Harrington, an investigator involved in the trial, remarked, "It is very encouraging to see statistical significance on important clinical outcomes in this relatively small study, which provides an excellent basis for advancing setanaxib in this hard-to-treat population."

A transcriptomic analysis of biopsy samples also revealed an increase in CD8+ T-cells in tissue from patients treated with setanaxib, suggesting a rise in tumor immunological activity that aligns with the drug's mechanism of action. This is seen as a positive indicator of the drug's potential efficacy.

Renée Aguiar-Lucander, CEO of Calliditas, noted, "This is a very exciting result, which provides clinical evidence of the mode of action of setanaxib in line with our thesis of its anti-fibrotic effects, and with results beyond our expectations for a study of this size." She added that no new safety concerns were identified during the trial.

Beyond SCCHN, Calliditas is also investigating setanaxib in several other conditions. The company's development program includes a mid-stage trial in primary biliary cholangitis, with results expected in the third quarter. Additionally, an investigator-led Phase II study in idiopathic pulmonary fibrosis is anticipated to produce top-line data by the end of the year. Calliditas is also conducting a Phase II trial in Alport syndrome, with results expected in the first half of 2025.

In summary, while setanaxib did not achieve its primary goal in the Phase II trial for SCCHN, it demonstrated significant improvements in secondary survival endpoints. These promising results suggest potential for further development and application of setanaxib in treating hard-to-manage cancers and other conditions, reinforcing Calliditas' commitment to advancing innovative therapies.