Findings from 2 Phase III trials of plecanatide were presented at Digestive Disease Week, held May 6-9 in Chicago, Illinois.
Findings from 2 Phase III trials of plecanatide were presented at Digestive Disease Week, held May 6-9 in Chicago.
Ronald Fogel, MD, of the Digestive Health Center of Michigan, began his presentation by outlining the current state of treatment for irritable bowel syndrome with constipation (IBS-C). Laxatives remain the most common therapy, but they have inconsistent effects on the abdominal pain associated with IBS-C.
“Many patients report being little or not at all satisfied with the effect of current therapies, and in addition to the inadequate treatment response, some patients experience adverse events,” he said.
Fogel said that the disease “represents a significant socioeconomic burden,” as patients on average incur over $4400 in gastrointestinal-related costs per year, $1300 of which are specific to IBS-C. There are also opportunity costs that accompany the syndrome, as many patients report missing days of work or school and report on average 60 days of disrupted productivity every year due to their symptoms.
He described the chemical structure of a promising new drug, plecanatide, and summarized the results of 2 phase III trials completed as the FDA reviews the drug’s use in treating adults with IBS-C. The 12-week trials assessed the safety and efficacy of plecanatide in 3 and 6 mg doses compared to placebo.
The FDA defined the primary endpoint for determining response to be a combination of abdominal pain and stool frequency measures. To meet this primary endpoint and be considered an “overall responder,” patients had to show both a decrease of at least 30% in abdominal pain score and an increase of 1 or more complete spontaneous bowel movements compared to baseline in the same week for 6 or more weeks of the 12-week study period.
“In both studies, plecanatide 3 mg and plecanatide 6 mg produced a significantly increased overall responder rate as compared to the placebo,” Fogel said, as well as for each of the 2 response components, abdominal pain and stool frequency.
Responses to the drug in both trials began in the first week of therapy, then increased and peaked around 6 weeks and leveled off for the remainder of the study period. After the drug was discontinued after 12 weeks, the effect of plecanatide gradually dissipated, according to Fogel. The researchers defined sustained efficacy as producing an overall response endpoint for at least 2 of the last 4 weeks of treatment, and observed that “plecanatide was better than placebo at producing a sustained efficacy response in these patients with IBS-C.”
Discussing adverse events, Fogel explained that diarrhea was the only treatment-related adverse events that was seen in more than 2% of patients and at higher rates than in the placebo arm, as 1% of the placebo group and 4% of the 2 plecanatide groups experienced diarrhea. There were no hospitalizations and no deaths during the trials.
“In summary, plecanatide is efficacious, safe, and has a low rate of diarrhea in patients with IBS-C,” Fogel concluded.
After the presentation, an audience member asked whether the results were clinically, as well as statistically, significant.
“Having done both sets of studies, I think it is clinically significant too,” Fogel replied. “For the patients who responded, they’re really very happy with their quality of life during the course of the study.”