Novartis said ligelizumab, a new treatment for chronic spontaneous urticarial (CSU), failed to prove superiority to the company’s existing CSU treatment Xolair (omalizumab) in phase 3 clinical trials.
On Monday, Novartis released top-line results from phase 3 PEARL 1 and PEARL 2 studies, saying ligelizumab showed superiority compared with placebo at week 12 but not compared with Xolair.
Ligelizumab is a high-affinity, monoclonal anti-immunoglobulin (Ig) E antibody.
In an earlier phase 2b trial, more patients had complete resolution of hives with ligelizumab than Xolair, which drew much anticipation for ligelizumab.
In a phase 2b extension study, ligelizumab solidified a potential to demonstrate a faster and better treatment outcome than Xolair in patients who were previously treated with Xolair.
Novartis ran a large-scale phase 3 trial program to prove ligelizumab’s efficacy with positive results in previous studies. However, the company faced an unexpected setback.
The PEARL 1 and PEARL 2 studies evaluated the efficacy and safety of ligelizumab in adult and adolescent patients aged 12 or more with CSU. However, they remain symptomatic despite H1-antihistamine treatment compared to placebo and Xolair.
The studies included more than 2,000 patients from 48 countries randomly assigned to ligelizumab 72 mg, ligelizumab 120 mg, omalizumab 300 mg, or placebo. The treatment was given every four weeks for one year. Patients initially grouped in placebo were switched to ligelizumab 120 mg from week 24 until the end of the treatment period.
The primary endpoint was set as the change from baseline in urticaria activity score over seven days (UAS7) at week 12, but ligelizumab was not superior to Xolair.
“We are disappointed that we have been unable to demonstrate superior efficacy for ligelizumab versus standard of care in the treatment of CSU,” said John Tsai, head of global drug development and chief medical officer at Novartis. “We will continue to evaluate the potential for ligelizumab to bring benefit to patients in the areas of chronic inducible urticaria (CIndU) and food allergy, where there is a significant unmet need.”
Novartis said it planned to disclose full data from PEARL 1 and PEARL 2 after completing the studies in the second half of 2022.
Evaluate Pharma, a global market researcher, had predicted that ligelizumab was expected to sell $652 million in 2026, saying ligelizumab was Novartis’ most valuable phase 3 asset.
Thus, industry watchers said that Novartis would find it hard to recover from the latest clinical failure.
In an article on Monday, Evaluate Pharma said that Novartis lost one of the most prospective pipelines.
“It is still in pivotal trials in CIndU and peanut allergy, but these readouts are much further off and, in any case, ligelizumab’s prospects here no longer look great,” it said.