The following written comments were submitted by IFFGD president, Ceciel T. Rooker, to the US Food and Drug Administration (FDA) in connection with a October 18, 2018 joint meeting of the FDA Gastrointestinal Drugs Advisory Committee and Risk Management Advisory Committee to discuss the reintroduction of Zelnorm:

The International Foundation for Gastrointestinal Disorders (IFFGD) commends the FDA on its commitment to ensuring the safety and effectiveness of treatments for conditions that impact the American public.

Established in 1991, IFFGD is a patient-driven nonprofit organization dedicated to assisting individuals affected by chronic gastrointestinal (GI) illnesses by providing education and support for patients, the family members, healthcare providers, and the public. IFFGD also works to advance critical research aimed at broadening our understanding of the basic mechanisms and clinical care of these conditions and providing patients with better treatment options, and perhaps one day, cures. IFFGD has worked closely with the FDA to facilitate greater involvement of the patient voice in health policy and regulatory decisions, including taking an active role in the 2015 FDA Patient-Focused Drug Development public meeting on Functional GI Disorders.

Today, I am writing to you regarding Docket No. FDA-2018-N-3223 for “Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting; Establishment of a Public Docket; Request for Comments” to discuss supplemental new drug application (sNDA) 021200, supplement 015, for ZELNORM (tegaserod maleate) for the treatment of women with irritable bowel syndrome (IBS) with constipation who do not have a history of cardiovascular disease and who do not present with more than one risk factor.

We applaud the FDA’s continued interest in investigating therapies on behalf of the millions of Americans living with IBS. IBS is one of the most common GI disorders in the general population, striking all demographic groups. It affects 30 to 45 million Americans; conservatively, at least 1 out of every 10 people. Between 9 to 23% of the worldwide population suffers from IBS, resulting in significant human suffering and disability. IBS as a chronic disease is characterized by a group of symptoms that may vary from person to person, but typically include abdominal pain associated with a change in bowel pattern, such as diarrhea and/or constipation. As a “functional disorder,” IBS affects the way the muscles and nerves work, but the bowel does not appear to be damaged on medical tests. Without a definitive diagnostic test, many cases of IBS go undiagnosed or misdiagnosed for years. It is not uncommon for IBS suffers to have unnecessary surgery, medication, and medical devices before receiving a proper diagnosis and appropriate care. Even after IBS is identified, treatment options are limited and treatment effectiveness varies widely from patient to patient or even for a single patient over his or her lifespan.

IBS can be emotionally and physically debilitating. Due to persistent pain and bowel unpredictability, individuals who suffer from this disorder may distance themselves from social events and work opportunities, and many may even fear leaving their home. Stigma surrounding bowel habits often acts as barrier to treatment, as patients are not comfortable discussing their symptoms with doctors. Because IBS symptoms are relatively common and not life-threatening, many people dismiss their symptoms or attempt to self-medicate.

At IFFGD, we hear from tens of thousands of individuals who live daily with IBS. In response to repeated concerns vocalized by patients regarding the burden of their illness, the stigma and isolation they experience as a result of their symptoms, and their frustration with the lack of effective treatments available, we have worked to incorporate the IBS patient perspective in research. First with the “IBS in the Real-World Survey” in 2002 (Attached), and more recently with an international survey in conjunction with the UNC Center for Functional GI and Motility Disorders. In 2009, IFFGD published “IBS Patients: Their Illness Experience and Unmet Needs” (Attached). The study of 1,966 patients in the community confirmed the severity and quality of life issues faced by IBS patients. Additionally, the survey painted a picture of bleak expectations on symptom improvement, satisfaction with treatment, and evaluating risk associated with medication.

More recently, findings of the BURDEN IBS-C study reported in Advances in Therapy (Quigley EMM, et al. 2018. https://doi.org/10.1007/s12325-018-0733-x) revealed that both patients with IBS-C and healthcare providers continue to be dissatisfied with current management pathways, with many patients self-treating with OTCs and laxatives or abandoning treatment without consulting a medical professional. For these patients, their symptoms cause considerable frustration and stress, with only 20% of respondents feeling like they are in control of their IBS-C.

Greater sensitivity to the impact of IBS symptoms on everyday life, increased awareness of IBS as a treatable medical condition, and greater availability of safe and effective treatment options are critical to improving outcomes and putting patient back in control of their symptoms. Industry, physicians, and regulatory agencies all have a role in this. The pharmaceutical industry needs to provide the data necessary for accurate analysis of the risks and benefits of the medication they develop, and they need to work closely with physicians, pharmacists, and patients to ensure clear and useful prescribing information. Physicians need to be well-informed about the experiences and perspectives of their patients with IBS and work alongside their patients to help them achieve their health goals. Finally, regulatory agencies, like the FDA, have an obligation to ensure that safe and effective medications are made available.

We urge the FDA to consider the impact IBS-C has on patients when looking at the risks and benefits of any medication approved to treat the condition. Questions have been raised about the safety and efficacy of tegaserod (ZELNORM). We ask that these questions be considered in the context of the risk/benefit ratio for IBS, taking into account the demonstrated burden posed by the condition on those affected and the need for treatment options. As adverse events are reported, we urge that mechanisms be in place to ensure that any possible causal relationship between the drug and the event is clearly supported. We urge consideration of how side effects can be managed before they reach a crisis point for patients. If tegaserod (ZELNORM) is shown to be safe and effective for adult women without risk for cardiovascular disease, it will represent the potential for symptom relief for many of those suffering with symptoms of IBS-C.

We thank you for the consideration of our comments and welcome the opportunity to work in conjunction with the FDA to obtain input from patients on the drug development process.