Janssen Terminates Izencitinib Collaboration with Theravance Following Disappointing Phase 2 Results in Inflammatory Bowel Disease

Compiled by Fan Dongdong

Xian Janssen, a subsidiary of Johnson & Johnson, recently announced the termination of its collaboration with Theravance Biopharma in San Francisco after the disappointing performance of an inflammatory bowel disease drug jointly developed by the two companies.

In 2018, Xian Janssen entered into a collaboration with Theravance for izencitinib, an oral, gut-selective JAK inhibitor aimed at treating ulcerative colitis and Crohn's disease. For this collaboration, Xian Janssen made an upfront payment of up to $100 million to Theravance and committed to an additional $900 million in potential milestone payments. The focal point of the collaboration, izencitinib, is an oral JAK inhibitor designed to block Janus kinase (JAK) enzymes involved in inflammation. Earlier in the same year, the company also struck another JAK inhibitor collaboration with Pfizer to co-develop a preclinical program for a skin-targeted, locally acting, rapidly metabolized pan-Janus kinase (pan-JAK) inhibitor. This deal included a $10 million upfront cash payment, with the potential to receive up to an additional $240 million in development and sales milestone payments from Pfizer.

However, in August this year, Theravance announced the failure of the Phase II clinical trial for the ulcerative colitis drug izencitinib. This Phase II trial recruited a total of 239 patients, who were randomly assigned to groups receiving one of three doses of izencitinib or a placebo, once daily for 8 weeks. According to the trial results reported by Theravance, there was no improvement in the severity of ulcerative colitis in patients receiving any dose of izencitinib. A trend of a slight dose-dependent increase in clinical response was observed, which the company attributed to a reduction in rectal bleeding.

In November that followed, another cardiac drug encountered failure in Phase III trials. Theravance ultimately had to announce a workforce reduction of 75%, laying off 270 employees. This layoff was part of the company's new strategic action plan, which it said would save $165 million and allow it to refocus on respiratory diseases. Theravance had previously brought two respiratory drugs to market, Yuperli and Trelegy, for the treatment of COPD. Both drugs generated actual revenue for Theravance, but not enough to offset the enormous expenses. In the first half of 2021, income from partnerships amounted to $21.2 million, while R&D-related expenditures were $175 million.

In addition, the company's two other wholly-owned respiratory disease candidate drugs are also being actively advanced. An inhaled JAK inhibitor for acute and chronic pulmonary inflammation is currently in Phase II research, while another is in Phase I asthma research. The day after the layoffs were announced, the company declared it would also halt the Phase II study of izencitinib for Crohn's disease. The company stated that after reviewing the relevant trial data, they deemed the drug safe but not particularly effective. With both studies of izencitinib now concluded, Johnson & Johnson has ultimately decided to terminate the collaboration. Year-to-date, Theravance's stock price has fallen nearly 40%.

Following the termination of Johnson & Johnson's collaboration deal on inflammatory bowel disease, the company’s stock price is poised to start falling again at any moment. However, inflammatory bowel disease continues to affect a growing number of Americans, with approximately 3 million people diagnosed with either Crohn’s disease or ulcerative colitis. For many patients, AbbVie’s Humira remains a viable option, offering symptom relief and enabling them to lead a normal life. Humira generated a staggering $20 billion in sales last year, including $16 million in the U.S. alone, making it the best-selling drug of 2020.

As biosimilars continue to gain approvals, the global inflammatory bowel disease market is also facing increased competition. Yusimry, a Humira biosimilar developed by Coherus BioSciences, has just received FDA approval in the U.S. this week and will enter the U.S. market before July 2023 alongside Hadlima from Samsung Bioepis, Hyrimoz from Sandoz, and Cyltezo from Boehringer Ingelheim. Therefore, as Theravance exits the inflammatory bowel disease market, many other companies will step in to fill the growing clinical demand gap.

Reference Source: Janssen Cuts Ties with Theravance After IBD Program Flop