FDA NewsPerspective

FDA advisory committee votes unanimously in favor of approval of prucalopride for chronic idiopathic constipation

By a 10-0 vote, the FDA Gastrointestinal Drugs Advisory Committee voted to approve prucalopride for chronic idiopathic constipation, according to a press release from Shire, its manufacturer.

“This investigational compound reinforces Shire’s long-standing heritage in gastrointestinal conditions and deep in-house capabilities in the category,” Andreas Busch, PhD, Shire’s head of research and development said in the release.

Prucalopride — a gastrointestinal prokinetic agent that improves bowel motility by stimulating colonic peristalsis — has been studied in more than 90 clinical trials worldwide over the last 20 years, according to Shire.

Woman with stomach pain 
By a 10-0 vote, the FDA Gastrointestinal Drugs Advisory Committee approved prucalopride for chronic idiopathic constipation, according to a press release from Shire, its manufacturer.

Source:Adobe

The company added that an integrated analysis of six main clinical trials showed significantly more patients treated with prucalopride (27.8%) vs. placebo (13.2%) achieved an average of three or more spontaneous, complete bowel movements each week over the 12-week treatment period.

According to Shire, there were 2,484 adult patients in the integrated efficacy analysis and 2,552 adult patients in the integrated safety analysis; all patients included received prucalopride less than or equal to 2 mg daily or placebo.

Additionally, adverse events that occurred in 5% of prucalopride recipients included abdominal pain, diarrhea, headache, and nausea, and the proportion of patients who experienced any adverse CV events were comparable between those who received prucalopride vs. those who received placebo.

The FDA has set prucalopride’s PDUFA date for Dec. 21.

 

By a 10-0 vote, the FDA Gastrointestinal Drugs Advisory Committee voted to approve prucalopride for chronic idiopathic constipation, according to a press release from Shire, its manufacturer.

“This investigational compound reinforces Shire’s long-standing heritage in gastrointestinal conditions and deep in-house capabilities in the category,” Andreas Busch, PhD, Shire’s head of research and development said in the release.

Prucalopride — a gastrointestinal prokinetic agent that improves bowel motility by stimulating colonic peristalsis — has been studied in more than 90 clinical trials worldwide over the last 20 years, according to Shire.

Woman with stomach pain 
By a 10-0 vote, the FDA Gastrointestinal Drugs Advisory Committee approved prucalopride for chronic idiopathic constipation, according to a press release from Shire, its manufacturer.

Source:Adobe

The company added that an integrated analysis of six main clinical trials showed significantly more patients treated with prucalopride (27.8%) vs. placebo (13.2%) achieved an average of three or more spontaneous, complete bowel movements each week over the 12-week treatment period.

According to Shire, there were 2,484 adult patients in the integrated efficacy analysis and 2,552 adult patients in the integrated safety analysis; all patients included received prucalopride less than or equal to 2 mg daily or placebo.

Additionally, adverse events that occurred in 5% of prucalopride recipients included abdominal pain, diarrhea, headache, and nausea, and the proportion of patients who experienced any adverse CV events were comparable between those who received prucalopride vs. those who received placebo.

The FDA has set prucalopride’s PDUFA date for Dec. 21.

 

    Perspective
    William D. Chey

    William D. Chey

    Chronic idiopathic constipation is a very common problem, affecting 14% of the general population worldwide. Just as the clinical phenotype is diverse, so too is the pathogenesis of the condition. Abnormalities in secretion, absorption, motility, and defecation have been implicated.

    The prescription treatments currently available for chronic idiopathic constipation have focused on stimulating chloride secretion, albeit by different mechanisms. Lubiprostone, linaclotide, and plecanatide have been shown to significantly improve stool frequency, as well as other important constipation-related complaints in patients with chronic idiopathic constipation. However, the range of therapeutic gain over placebo is 10-18% and fewer than a quarter of patients with the condition treated with these medications in the phase 3 trials met the primary endpoint. Of at least equal importance to the data from clinical trials are studies that have found that a significant minority of patients with chronic idiopathic constipation are not satisfied with their current treatment making clear that there remains an unmet need for novel treatments for chronic idiopathic constipation.

    5-HT4 agonists stimulate peristalsis and may also exert effects on visceral sensation. Numerous studies have demonstrated the benefits of the 5-HT4 agonist prucalopride for stool frequency and other key constipation symptoms in patients with chronic idiopathic constipation. The currently available literature does not provide clear evidence of increased cardiovascular risk in patients treated with prucalopride.

    Ultimately, the FDA will need to agree with this assessment for prucalopride to find its way to patients with chronic idiopathic constipation in the United States. Assuming that turns out to be the case, providers should be reminded that there are no comparative effectiveness studies between neither currently available prescription medications for this condition nor with prucalopride. Thus, pricing, formulary access, and provider preferences will play a large role in which patient gets which therapy in which order.

    Certainly, providers will welcome the different mechanism of action offered by a 5-HT4 agonist. Of note, 5-HT4 agonists exert effects on motor activity in the upper as well as lower gastrointestinal tract, acknowledging that effects in the upper gastrointestinal tract vary from compound to compound. This attribute differentiates 5-HT4 agonists from other currently available over-the-counter and prescription treatments for chronic idiopathic constipation and may make them an attractive choice for patients with overlapping upper and lower gastrointestinal symptoms, though this remains to be proven in methodologically rigorous clinical trials.

    References:

    Camilleri M, et al. Nat Rev Dis Primers. 2017;doi:10.1038/nrdp.2017.95.

    Johanson JF, et al. Am J Gastroenterol. 2008; Jan;103(1):170-7.

    Lembo AJ, et al. N Engl J Med. 2011;doi:10.1056/NEJMoa1010863. Minor PB, et al. Am J. Gastroenterol. 2017; Apr; 112(4): 613–621.

    Tack J, et al. Aliment Pharmacol Ther. 2012;35:745-67.

     

    • William D. Chey, MD, AGAF, FACG, FACP, RF
    • professor of gastroenterology and nutrition sciences
      University of Michigan

    Disclosures: Healio Family Medicine was unable to determine Chey’s relevant financial disclosures prior to publication.