After a string of Big Pharmas reported failures for their BTK inhibitors in autoimmune disorders, Novartis finally appears to have a winner.
The Swiss pharma reported that remibrutinib has succeeded in controlling the autoimmune condition chronic spontaneous urticaria, or CSU, which causes unpredictable hives and swelling that can be painful and itchy. The disease flairs up randomly and the hives and swelling can occur for six weeks or more and return over a period of one to five years.
Remibrutinib was tested in a phase 2b trial of patients with inadequately controlled CSU to evaluate the therapy’s safety and efficacy. The main goal was to determine whether the drug elicited a dose-dependent response compared to placebo at week four, which was met.
Novartis reported that the therapy provided significant improvements in patients at all dose levels, and the results appeared rapidly in the first week. When compared with placebo, more patients who took any dose of remibrutinib achieved complete control without hives or itch or had well-controlled disease until treatment ended.
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Safety was favorable and good tolerability was reported across dose levels.
Remibrutinib is a BTK inhibitor, a target that has been used successfully in cancer but has proven tricky for pharmaceutical companies in autoimmune disorders. Bristol Myers Squibb, Gilead, Eli Lilly, Roche and Sanofi have all had high-profile failures or other challenges trying to bring forward a BTK inhibitor in this type of disease.
Most recently, a treatment that Sanofi picked up in the $3.7 billion buyout of Principia Biopharma flunked a phase 3 trial in the rare autoimmune skin disease pemphigus. Principia had been planning to use the results from that late-stage test of rilzabrutinib to support a filing, but that plan seems to be off the table for now.
Enter Novartis, which now has the BTK inhibitor results that could support further investigation in autoimmune disorders. The company has dubbed remibrutinib “a potentially best-in-class oral BTK inhibitor.”
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Novartis also has the monoclonal anti-immunoglobulin antibody ligelizumab under development in CSU. Both ligelizumab and remibrutinib will complement Xolair, which is approved as an add-on treatment for the condition. That therapy was developed with Roche’s Genentech in the U.S., while Novartis markets and records sales in other regions.
Sanofi, however, is trudging on with rilzabrutinib in a phase 3 test for the rare blood disorder immune thrombocytopenia and a mid-stage study for patients with IgG4-related disease. Further tests are planned in asthma, atopic dermatitis, CSU and warm autoimmune hemolytic anemia. The company still believes that the therapy can become a “pipeline in a product.”
Novartis also sees a bright future for remibrutinib, formerly known as LOU064, in other immune-mediated diseases. The therapy is listed for a number of CSU indications on the FDA's clinical trials tracker, as well as for Sjögren's Syndrome. The company also conducted a phase 2 trial in patients with uncontrolled asthma, but the study is listed as terminated as of April 2021.