A New Drug Application was submitted to the FDA seeking accelerated approval of eflornithine in combination with sulindac for the treatment of adult patients with familial adenomatous polyposis.
A New Drug Application (NDA) seeking accelerated approval of eflornithine (CPP-1X) in combination with sulindac (CPP-1X/sul) for the treatment of adult patients with familial adenomatous polyposis has been submitted to the FDA, announced Cancer Prevention Pharmaceuticals in a press release.
Familial adenomatous polyposis, a rare genetic disease, is known to progress to colorectal cancer in almost 100% of patients when left untreated. A fixed-dose combination of this regimen may be a potential pharmaco-preventative treatment of familial adenomatous polyposis.
“The NDA submission for our lead drug candidate, CPP-1X/sul, represents a significant milestone for familial adenomatous polyposis patients and their families,” said Jeff Jacob, chief executive officer, Cancer Prevention Pharmaceuticals, in a statement. “For most familial adenomatous polyposis patients, current medical practice involves a lifetime of periodic monitoring as well as highly invasive surgical procedures. If approved, CPP-1X/sul could provide an alternative to surgery for many patients, significantly improving their quality of life.”
In a clinical trial, the combination of CPP-1X/sul prevented > 90% subsequent pre-cancerous sporadic adenomas compared with placebo in patients with large bowel polyps. The combination was moved to the pivotal phase 3 CPP FAP-310 clinical trial, which compared the same combination to each drug alone.
Results from this trial, which were published in June 2019, showed that the combination did not demonstrate statistical significance compared with eflornithine alone or sulindac alone in the lower versus upper gastrointestinal (GI) anatomy. However, there was a statistically significant benefit for the combination compared with both single agents in the lower GI anatomy, which included patients with an intact colon, retained rectum, or surgical pouch.2
In patients with lower GI disease, the benefit in delaying surgical events for up to 4 years was observed in the combination arm compared with the single agents (P ≤.02). There were no significant differences in the safety profile of the combination compared with the single agents, and the combination did not pose any new concerns for long-term use.
“With up to four years of treatment, the combination appears to greatly delay the need for major surgeries in the colon, rectum, or surgical pouch. We hope that this new drug regimen will soon be available as an adjunct in the management of FAP patients facing large bowel surgery,” stated Alfred Cohen, MD, chief medical officer of Cancer Prevention Pharmaceuticals.
The trial enrolled 171 patients across 17 institutions in the United States, Canada, and Europe, and was the largest prospective, controlled study performed in patients with familial adenomatous polyposis. Patients were treated for up to 48 months, which is much longer than in any other clinical trial for this patient population.
CPP FAP-310 was designed to evaluate if the combination is superior to the single agents in delaying time to first occurrence of a familial adenomatous polyposis-related event. Patients with lower and upper GI disease were included in the study.
CPP-1X/sul has previously received an Orphan Drug designation from the FDA for this disease.1
Familial adenomatous polyposis occurs in 1 in about every 10,000 people in the United States, and the current recommendation for treatment is a lifetime of monitoring with surgical procedures for disease-related events. This may include surgical removal of the colon, rectum, surgical pouch, duodenum, and high-risk adenomas. There are no approved treatment options for this patient population.2
Cancer prevention pharmaceuticals submits new drug application to the FDA for CPP-1X/sul for treatment of familial adenomatous polyposis. News Release. Cancer Prevention Pharmaceuticals. June 20, 2019. Accessed June 29, 2020. https://bwnews.pr/3eKzSnU
Cancer prevention pharmaceutical (CPP) reported FAP phase 3 clinical trial results at digestive disease week conference. News Release. Cancer Prevention Pharmaceuticals. June 20, 2019. Accessed June 29, 2020.