Theravance Drug Candidate Izencitinib Fails To Meet Primary Endpoint
Izencitinib didn't meet the primary endpoints in its phase IIb study.
In a statement, the firm said that while the drug, izencitinib, was generally well tolerated and its safety data were consistent with expectations, it failed to achieve its primary endpoint of seeing a change in the total Mayo score at week eight, compared to the placebo. Izencitinib is an oral, gut-selective pan-Janus kinase (JAK) inhibitor in development to treat ulcerative colitis. JAK inhibitors are currently approved for immune-mediated diseases, such as myelofibrosis, rheumatoid arthritis, and ulcerative colitis.
The Mayo Score is a group of subscores ranging from 0 to 12 based on four categories, including rectal bleeding, stool frequency, colonoscopy or proctosigmoidoscopy findings, and a doctor's global assessment.
Izencitinib Phase IIb Study
The Phase IIb study reportedly saw a small dose-dependent increase in clinical response, driven by a reduction in rectal bleeding. Apart from that, there was no significant change. At all doses, izencitinib did not show any notable changes in lab values, including creatine phosphokinase and lipids, while its plasma exposure remained low, consistent with the expectations for gut-selective medicine.
"We had high expectations for the Phase IIb study after eight weeks of treatment with izencitinib in ulcerative colitis given the totality and consistency of the broad range of clinical, histologic, and biomarker data we saw in the Phase Ib study with only four weeks of treatment, albeit in a small number of patients. We plan to analyze the data to better understand the findings and the potential for optimization of a gut-selective medicine as a treatment for patients with inflammatory bowel diseases," said Rick E. Winningham, chief executive officer of Theravance.
Winningham added that their trial for the Crohn's Phase II study is ongoing and that the company expects to report top-line results either toward the end of the 2021 fourth quarter or early first quarter 2022. It has not given up on izencitinib yet.
The company will continue to explore the results and implications for the drug as it moves forward into week 16 of the trial's induction portion and its 44-week maintenance period. However, in relation to ulcerative colitis, Theravance said it would find ways to minimize future related expenses.
Izencitinib is at the core of the strategic collaboration between Theravance and Janssen Biotech, who agreed to co-develop and commercialize the drug for treating inflammatory intestinal diseases. Under the terms of their deal, Theravance received an upfront payment of $100 million and is set to accept as much as $900 million more in payments if Janssen chooses to stay in the partnership after specific Phase II activities are completed. Should these succeed, the two firms will jointly develop izencitinib and launch a Phase III program in the U.S.