FDA NewsPerspective

FDA approves reintroduction of Zelnorm for IBS-C in certain women

The FDA has approved the reintroduction of Zelnorm, a twice-daily oral treatment for irritable bowel syndrome with constipation in women aged under 65 years, according to a company press release.

The FDA originally approved tegaserod (Zelnorm, Sloan Pharmaceuticals) in 2002 for the treatment of IBS-C in women. However, Novartis, the drug’s previous manufacturer, voluntarily pulled tegaserod from the U.S. market in 2007 due to possible cardiac-related side effects.

Tegaserod has been available in the U.S., but only through an FDA-authorized expanded access program.

“We are excited about what the reintroduction of Zelnorm means for patients suffering from irritable bowel syndrome with constipation,” P. Breckinridge Jones, CEO of U.S. WorldMeds, said in the press release. “We have continually heard from patients and clinicians alike that the IBS-C community is eager to have Zelnorm return to the U.S. as an available treatment option.”

The approval to reintroduce tegaserod, according to the release, is a result of a complete safety review from the FDA and the FDA Gastrointestinal Drugs Advisory Committee (GIDAC).

The review evaluated clinical data from 29 placebo-controlled trials, as well as newly-available sources of treatment outcome data.

A selective serotonin-4 (5-HT4) receptor agonist, tegaserod targets the 5-HT4 receptor across multiple neurons and smooth muscle cells in the gastrointestinal tract to induce contraction and relaxation, and decrease pain signaling.

Results of three double-blind, placebo-controlled trials that comprised 2,470 adult women demonstrated symptom improvement from baseline after 1 month of receiving tegaserod compared with placebo, according to the release.

Sloan Pharmaceuticals, a subsidiary of U.S. WorldMeds, acknowledged in the release that there remains an increased risk for cardiac events, including myocardial infarction and stroke, when using tegaserod.

The FDA has approved the reintroduction of Zelnorm, a twice-daily oral treatment for irritable bowel syndrome with constipation in women aged under 65 years, according to a company press release.

The FDA originally approved tegaserod (Zelnorm, Sloan Pharmaceuticals) in 2002 for the treatment of IBS-C in women. However, Novartis, the drug’s previous manufacturer, voluntarily pulled tegaserod from the U.S. market in 2007 due to possible cardiac-related side effects.

Tegaserod has been available in the U.S., but only through an FDA-authorized expanded access program.

“We are excited about what the reintroduction of Zelnorm means for patients suffering from irritable bowel syndrome with constipation,” P. Breckinridge Jones, CEO of U.S. WorldMeds, said in the press release. “We have continually heard from patients and clinicians alike that the IBS-C community is eager to have Zelnorm return to the U.S. as an available treatment option.”

The approval to reintroduce tegaserod, according to the release, is a result of a complete safety review from the FDA and the FDA Gastrointestinal Drugs Advisory Committee (GIDAC).

The review evaluated clinical data from 29 placebo-controlled trials, as well as newly-available sources of treatment outcome data.

A selective serotonin-4 (5-HT4) receptor agonist, tegaserod targets the 5-HT4 receptor across multiple neurons and smooth muscle cells in the gastrointestinal tract to induce contraction and relaxation, and decrease pain signaling.

Results of three double-blind, placebo-controlled trials that comprised 2,470 adult women demonstrated symptom improvement from baseline after 1 month of receiving tegaserod compared with placebo, according to the release.

Sloan Pharmaceuticals, a subsidiary of U.S. WorldMeds, acknowledged in the release that there remains an increased risk for cardiac events, including myocardial infarction and stroke, when using tegaserod.

    Perspective
    William D. Chey

    William D. Chey

    I’m excited to have prucalopride and, now with this most recent approval, tegaserod available in the United States.

    For many years now, we in the U.S. have not had access to effective prokinetic therapies for patients with chronic idiopathic constipation, or IBS with constipation in the case of tegaserod.

    There has clearly been a tremendous amount of pent up demand for prokinetic options, because the reality is that none of the individual constipation therapies make every patient better. In fact, when looking at the data, approximately 50% or less of patients respond to any of the individual drugs that are currently FDA-approved for constipation.

    This is not because the drugs are ineffective, but rather because the pathogenesis of constipation-related symptoms is heterogeneous, so having drugs that work by different mechanisms at least offers a possibility of finding a solution for patients that have the same symptoms, but not necessarily the exact same disease.

    While tegaserod was previously removed for the U.S. market because of concerns surrounding increased risks for cardiovascular events, there have subsequently been studies that have evaluated large databases and found no association between tegaserod and increased risks for cardiovascular events.

    To reinforce that point, the FDA hosted an advisory board meeting in October 2018 where they reviewed the literature relevant to a potential increased risk for cardiovascular events in patients taking 5-HT4 receptor agonists, including tegaserod, and concluded that there was no clear evidence of an increased cardiovascular risk. Both the drugs within that class that were brought in front of the FDA were ultimately approved. Prucalopride was approved for patients with CIC while tegaserod was approved for the treatment of IBS-C in females 65 years and younger without a history of ischemic CV disease.

    5-HT4 agonists such as prucalopride and tegaserod may be particularly attractive in patients that have overlapping upper and lower GI symptoms because these drugs not only effect colon transit, but gastric emptying as well.

    At the end of the day, probably 30% to 40% of patients who have constipation also have dyspeptic symptoms. We now have drugs that can potentially address both sets of symptoms, however it is important to note that the FDA has not approved either therapy for dyspepsia or gastroparesis.

    • William D. Chey, MD, AGAF, FACG
    • Timothy T. Nostrant Collegiate Professor of Gastroenterology & Nutrition Sciences
      Medical Director, Michigan Bowel Control Program
      Michigan Medicine

    Disclosures: Chey reports serving as a consultant for Shire and Takeda, as well as on an advisory board for U.S. WorldMeds.

    Perspective
    Zubair Malik

    Zubair Malik

    It’s great to have tegaserod back on the market. Although its use is limited to women aged under 65 years without any previous ischemic cardiac disease, what is even more limited is our access to promotility drugs that can help with constipation.

    Many patients don’t respond to our current medications. Promotility drugs such as tegaserod or prucalopride are great additions to our current medications because they work by using a different mechanism. The more different mechanisms of actions we have available to us, the better chances we have to be able to manage constipation.

    While there is some theoretical risk for cardiac complications, the FDA reviewed the literature and concluded there is no increased risk associated with the use of tegaserod.

    Another nice feature associated with tegaserod is that it has promotility effects on the entire GI tract, so it may have additional benefit in patients who have gastroparesis as well as constipation.

    • Zubair Malik, MD
    • Assistant Professor of Medicine
      Lewis Katz School of Medicine at Temple University
      Medical Director, Esophageal Program
      Associate Director, GI Motility Lab
      Temple University Hospital

    Disclosures: Malik reports no relevant financial disclosures.