Dive Brief:
- Protagonist Therapeutics Inc. has stopped a Phase 2b study after its lead drug PTG-100 failed to meet the requirements of an Independent Data Monitoring Committee following an interim analysis of the primary endpoint of clinical remission.
- The oral GI-restricted alpha-4-beta-7 integrin antagonist peptide is in development to treat moderate-to-severe ulcerative colitis. No further patients will be randomized into the study, and treatment of enrolled patients will end.
- Protagonist has put a planned Phase 2/3 trial of PTG-100 in chronic pouchitis on hold as well. The company's shares closed Monday trading down 56%, but recovered some of those losses Tuesday morning.
Dive Insight:
The mid-stage study, known as PROPEL, of PTG-100 in moderate-to-severe ulcerative colitis began in January 2017, with an aim to enroll 240 patients.
Topline data was expected in the second half of 2018. However, things didn't quite work to plan. In an interim analysis of the unblinded efficacy and safety data from the first 65 patients, the data monitoring committee "deemed the trial to be futile based on an analysis of the primary endpoint of clinical remission."
The next steps for PTG-100 are now unclear.
"We are very disappointed with this futility-based outcome which was also accompanied by an unexpectedly high placebo rate," Protagonist CEO Dinesh Patel said in a statement. "We will conduct an extensive review of the complete dataset on the totality of patients enrolled in the trial before making any further decisions about the future development of PTG-100."
Patel added the company plans to continue work on its other peptide-based therapeutics in clinical development. Johnson & Johnson has exclusive worldwide rights to co-develop and market Protagonist's IL-23 inhibitor PTG-200, in a deal that could be worth over $1 billion. The oral peptide moved into a Phase 1 trial in November 2017, and is in development in inflammatory bowel disease.
PTG-300, a subcutaneous injectable hepcidin mimetic for the treatment of beta-thalassemia, has orphan drug designation and has completed a Phase 1 trial. A global trial is planned, following discussions with U.S. and European regulatory agencies.
While there are injectable integrin antagonists in development and on the market for ulcerative colitis, few companies are taking the oral route. Eisai Inc. is developing carotegrast methyl (AJM300), an oral alpha-4 integrin antagonist in Phase 3 trials for the treatment of ulcerative colitis.