Calliditas' survival data rescues midphase cancer trial after primary endpoint failure

Calliditas Therapeutics saw fluctuations in its stock price recently, experiencing initial gains before reverting to its original value. This volatility followed updates on the company's midphase study of a treatment for head and neck cancer.

The Swedish biotech company embarked on a phase 2 trial to evaluate the effects of adding its experimental drug, setanaxib, to Merck & Co.'s Keytruda, a PD-1 checkpoint inhibitor. Setanaxib aims to inhibit the NOX1 and NOX4 enzymes, which are produced by cancer-associated fibroblasts (CAFs) in solid tumors. High levels of CAFs are often linked to poor survival rates and resistance to immunotherapy.

Calliditas devised a plan to enhance the penetration of immune cells into tumors, making checkpoint inhibitors more effective. The phase 2 trial involved 55 patients with recurrent or metastatic head and neck cancer. The primary goal was to determine the best percentage change from baseline in tumor size.

Unfortunately, setanaxib did not perform better than the placebo in terms of reducing tumor size. While Calliditas has not yet revealed the response rates, which are commonly reported in midphase trials, it did note that 70% of patients on setanaxib experienced at least stable disease, compared to 52% of those on placebo.

The company's focus shifted to progression-free survival (PFS) and overall survival (OS) outcomes. Results showed that the median PFS was five months for patients on setanaxib, compared to 2.9 months for the placebo group. Additionally, the nine-month OS rate was 88% for the setanaxib group and 58% for the placebo group. A similar trend was observed in OS rates after six months.

Despite the failure to meet the primary endpoint, Chief Medical Officer Richard Philipson emphasized the significance of reducing tumor size in this stage of development. In an earnings call in February, Philipson stated, “We think this is an important endpoint in a study at this stage of development. It’s a little bit more sensitive than just looking at response rates. Clearly, what we want to see is a significant reduction in tumor size in patients who are receiving setanaxib on top of pembrolizumab versus patients who are receiving placebo on top of pembrolizumab.”

Calliditas has not yet provided an explanation for why patients on setanaxib might have longer survival rates if the drug shows no effect on tumor size. The company plans to hold a research and development day later this month to present additional insights from the phase 2 trial and other data supporting the action mechanism of setanaxib.

The mixed results left investors uncertain, causing Calliditas' stock to initially rise before falling back to its opening price.

In summary, Calliditas’ phase 2 trial of setanaxib did not achieve its primary goal of reducing tumor size but showed promising signs in terms of progression-free and overall survival. The biotech firm plans to provide further details, potentially shedding light on the observed outcomes and future directions for setanaxib's development. Investors remain cautious as they await more comprehensive data and explanations.