Theravance takes a gut punch as J&J-partnered JAK drug flops key test in ulcerative colitis
When J&J signed a $100 million check away to biotech Theravance back in 2018, the drug giant saw some promise in the company’s lead “pan-JAK” drug in inflammatory bowel disease. A key trial checkpoint for that is now officially a dud — and the J&J deal may be dead in the water as well.
Theravance’s izencitinib, a “gut-selective” JAK inhibitor developed for ulcerative colitis and Crohn’s disease, failed a key Phase II test, giving the company no choice but to slice R&D costs on that program and send investors running for the hills. A planned Phase III study in UC also won’t be happening, executives confirmed on a Monday call with analysts.
In the eight-week induction portion of the Phase II trial, izencitinib failed to show benefit over placebo on the Mayo score improvement primary endpoint or clinical remission, a key secondary endpoint. The drugmaker noted “a small dose-dependent increase in clinical response” measured by Mayo, but not enough to drive significant benefit.
Despite Theravance waiting on follow-up, 16-week data in UC and a Phase II readout in Crohn’s, investors weren’t assuaged. Shares in $TBPH were trading down around 22% after the bell.
The Crohn’s data are due as early as Q4, offering another inflection point for the biotech. As it awaits those results, Theravance will cut its R&D costs for the izencitinib program, signaling its lack of belief in the drug’s commercial future.
“We had high expectations for the Phase 2b 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 1b study with only four weeks of treatment, albeit in a small number of patients,” CEO Rick Winningham said in a statement. “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.”
Theravance highlighted that all doses up to 200 mg were generally well-tolerated with 13 serious side effects reported but none related to izencitinib. That’s no small result for a JAK inhibitor, a drug class with a history of deleterious side effects, but not worth much without clinical efficacy to show.
The trial failure likely leaves Theravance’s development deal with Janssen for izencitinib (TD-1473) — and a $200 million opt-in milestone — in the wind. The partners signed that deal for $100 million cash back in 2018, with J&J jumping on board the biotech’s pipeline promise for tissue-selective JAK drugs.
With that cash now likely not coming, Theravance is in the process of “flexing all aspects of our capital structure to make sure we can keep the company fully funded,” CFO Andrew Hindman said on the Monday call.
“We do have a number of elements ongoing, and the impact to our guidance in 2021 is likely to be negligible,” VP of development Richard Graham added. “It’s really about the direction of the company in 2022 and beyond where we’ll be doing a lot of work internally.”