J&J, Theravance's izencitinib fails Phase II ulcerative colitis trial

Shares in Theravance Biopharma tumbled about 22% in after-hours trade on Monday after the company said izencitinib did not meet the primary endpoint of a Phase IIb trial of patients with ulcerative colitis (UC). Theravance, which is co-developing the oral, gut-selective pan-JAK inhibitor with Johnson & Johnson, indicated that another Phase II data readout of the drug in Crohn's disease is due late in the fourth quarter or early in the first quarter of 2022, but that based on the UC results, it will seek to "minimise" future expenses associated with the izencitinib programme.

The dose-finding induction study top-lined Monday randomised 239 adults with moderately-to-severely active UC to receive izencitinib or placebo, administered orally for eight weeks. The primary endpoint was the change in total Mayo score – calculated as a sum of four components; namely rectal bleeding, stool frequency, physician's global assessment and Mayo endoscopic subscore – from baseline through to eight weeks.

Results showed no significant change in the total Mayo score, nor on the key secondary goal of clinical remission at week eight, relative to placebo. Theravance noted there was "a small dose-dependent increase in clinical response measured by the adapted Mayo score, which was driven by a reduction in rectal bleeding."

Meanwhile, all doses of izencitinib were well-tolerated, with adverse event rates similar among patients receiving izencitinib and placebo. There were also no cases of perforation, opportunistic infection, major cardiovascular or thromboembolic events, complicated zoster, or non-melanoma skin cancer in patients receiving izencitinib. "Plasma exposure of izencitinib was low, consistent with expectations for a gut-selective medicine," the company said. It planned to use data from the study to determine induction and maintenance dose regimens for a confirmatory Phase III induction trial and the ongoing maintenance study. Theravance says it will present the UC results at a scientific forum.

'High expectations'

"We had high expectations…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," remarked Theravance CEO Rick Winningham. He said the company will be analysing the UC results "to better understand the findings and the potential for optimisation of a gut-selective medicine as a treatment for patients with inflammatory bowel diseases." Forthcoming UC data will include results from the 16-week extended induction portion of the trial and the 44-week maintenance study.

Theravance and Johnson & Johnson entered into their partnership for izencitinib, formerly TD-1473, in 2018. The deal included an upfront payment of $100 million to Theravance, which is also eligible to receive up to an additional $900 million in potential payments if Johnson & Johnson chooses to stay in the collaboration after certain Phase II activities are completed. If it does, the pair will jointly develop and commercialise izencitinib in inflammatory intestinal diseases, sharing expenses related to a potential Phase III programme and profits in the US.