Digestive Health Matters Vol. 22 No. 2
- GERD Awareness Week
- Babies Spitting Up - Normal In Most Cases
- Clinical Corner: A Question on Functional Abdominal Pain
- A Conversation with Douglas A. Drossman, M.D.
- Functional Abdominal Pain Syndrome
- About Clinical Trials
- Be an Active Member of Your Health Care Team
Here are summaries of some recent news about research and treatments for digestive health.
On June 11, 2013 Salix announced that the U.S. Food and Drug Administration (FDA) will be holding an advisory committee to review Salix’s Supplemental New Drug Application, which seeks to extend the use of Relistor to include patients who are taking opioids to treat chronic pain.
Relistor was approved in the United States in 2008 for short term treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care when response to laxative therapy has not been sufficient. It has also received approval for this indication in other countries.
Ferring Pharmaceuticals announced in May 2013 that it has entered Phase 3 trials of elobixibat for the indication of chronic idiopathic constipation (CIC). Two studies are being conducted at close to 200 sites around the world.
Elobixibat is a first-in-class compound under investigation for treatment of CIC and for IBS with constipation (IBS-C). It works by reducing bile acid absorption in the small intestine. This stimulates bowel movements by increasing fluid secretions and motility in the colon.
In Phase 2b clinical trials, elobixibat (formerly A3309) has been evaluated in patients in the U.S. and Europe for the treatment of CIC. The studies demonstrated clinically meaningful, statistically significant, and dose-dependent improvements. These included increased stool frequency and improved constipation-related symptoms such as straining, stool consistency, and bloating maintained over eight weeks of treatment.
On June 12, 2013 Ironwood Pharmaceuticals and Forest Laboratories announced that linaclotide is available in some countries in Europe (Germany, the UK, and Nordic countries) to treat IBS with constipation (IBS-C). It will become available in more European countries during 2013 with the EU brand name Constella.
Linaclotide, a guanylate cyclase type-C (GC-C) agonist, is a prescription drug used to relieve symptoms of abdominal pain, discomfort, bloating, and bowel symptoms in people who have IBS-C or chronic constipation (CC). It has been shown to be safe and effective in trials. Linaclotide works by increasing the amount of fluid that flows into the bowel, allowing stool to pass more easily, and reducing visceral pain.
Linaclotide (Linzess) has been available in the U.S. to treat IBS-C and CC in adults aged 18 and older since 2012.
Linzess should not be used in patients 17 years of age or younger. Linzess should not be used in patients with known or suspected mechanical gastrointestinal obstruction. The most common side effect reported during clinical studies was diarrhea.
Linaclotide is being co-produced in the U.S. by Ironwood and Forest. Ironwood has out-licensed linaclotide to Almirall, S.A. for development in Europe; and to Astellas Pharma, Inc. for development in Japan, Indonesia, Korea, the Phillipines, Taiwan, and Thailand.
Rifaximin is an antibiotic currently under investigation for the treatment of non-constipation IBS (Non-C IBS) and IBS-related bloating. Rifaximin works by reducing or altering bacteria in the gut. In studies it has been found to improve IBS symptoms of bloating, belly pain, and diarrhea (watery or loose stools) after a 10–14 day course of treatment. It is only slightly absorbed in the gut and is generally tolerated well. Rifaximin has not yet been approved by the U.S. Food and Drug Administration (FDA) for the treatment of IBS.
In April 2013 Sucampo Pharmaceuticals, Inc. and Takeda Pharmaceuticals U.S.A. Inc. announced that the U.S. Food and Drug Administration (FDA) approved the supplemental New Drug Application for lubiprostone (Amitiza) to treat opioid-induced constipation in adult patients with chronic non-cancer pain. The drug was approved to treat chronic idiopathic constipation (CIC) in adults in 2006 and to treat IBS with constipation (IBS-C) in adult women in 2008.
Amitiza is a prescription drug used to relieve stomach pain, bloating, and straining and produce softer and more frequent bowel movements in men and women who have CIC. It is also used to treat IBS-C in women who are at least 18 years of age. Amitiza works by increasing the amount of fluid that flows into the bowel and allowing the stool to pass more easily.
Lubiprostone met the primary endpoint in a phase 3 clinical trial for the treatment of opioid-induced bowel dysfunction in patients with chronic, non-cancer pain, excluding those taking methadone. Opioids are narcotics (such as morphine and codeine) used to treat pain. A number of gastrointestinal (GI) symptoms are potential side effects of using opioidbased medications. The most common symptom is constipation. Other symptoms may include decreased gastric emptying, abdominal cramping, spasm, bloating, and delayed-GI transit.
An international, multi-center study of teduglutide (Gattex) took place in January 2013, looking at the safety, tolerability, and efficacy of the drug taken once per day over 52 weeks for the treatment of people with short bowel syndrome (SBS) receiving parenteral nutrition (PN). The study concluded that, for patients with SBS and intestinal failure, the efficacy of teduglutide was maintained over 52 weeks and the safety profile was sufficient to be considered for long-term use.
Gattex is a product of NPS Pharmaceuticals, a specialty pharmaceutical company developing orphan therapeutics for rare gastrointestinal and endocrine disorders. It is a novel peptide involved in gastrointestinal regeneration and repair (recombinant analog of human glucagon-like peptide 2). Gattex works by regeneration of cells in the intestinal lining, slowing down transit through the gut and increasing blood flow, allowing for increased nutrient absorption. In studies, the drug was associated with achieving and maintaining clinically meaningful reductions in PN and IV fluid volume in adult subjects with SBS.
SBS is a rare condition related to poor absorption of nutrients. It typically occurs in people who have a significant portion of their small intestine removed due to disease or injury and cannot absorb enough water, vitamins, and other nutrients from food. They may then need to use PN and intravenous (IV) fluids, the slow infusion of a solution of nutrients and fluids into a vein.
While the researchers found the safety profile to be acceptable, they advise that physicians closely monitor patients beginning the drug for side effects and possible need to adjust dosage.
Teduglutide (Gattex) was approved by the U.S. Food and Drug Administration (FDA) in 2012 for treatment of adult patients with SBS who are receiving PN support. To help ensure that the benefits of Gattex outweigh the risks for causing other serious conditions, the drug is approved with a Risk Evaluation and Mitigation Strategy, which patients need to discuss with their doctors.
The European Commission granted European market authorization in August 2012 for the medicinal product teduglutide (trade name in Europe: Revestive) as a once-daily treatment for patients with SBS. In March 2013, NPS reacquired the rights to teduglutide outside of the U.S., Canada, Mexico, and Israel from Takeda GmbH.
Solesta, a biocompatible tissue bulking agent, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of fecal incontinence in patients 18 years and older who have failed conservative therapy (e.g., diet, fiber therapy, anti-motility medications). The drug has been approved to treat fecal incontinence in the U.S. since 2011 and in Europe since 2006.
Fecal incontinence is the involuntary loss of bowel control. While the exact mechanism of action has not been identified, it is thought that the Solesta injections may narrow the anal canal and allow for better control of those muscles.
Solesta is an injectable gel delivered into the anal canal in an outpatient procedure taking approximately 10 minutes without the need for surgery or anesthesia. It should only be administered by physicians experienced in performing anorectal procedures who have successfully completed a comprehensive training and certification program in the Solesta injection procedure. It should not be used in patients who have active inflammatory bowel disease, immunodeficiency disorders, previous radiation treatment to the pelvic area, significant rectal prolapse, active infections, bleeding, tumors or malformations in the anorectal area, rectal distended veins, an existing implant in the anorectal region, or allergy to hyaluronic acid based products.
The most common side effects associated with Solesta include injection area pain and bleeding. Infection and inflammation of anal tissue are more serious risks, but are less common.
Solesta is a registered trademark of Q-Med AB of Uppsala, Sweden; Oceana Therapeutics acquired exclusive worldwide sales and distribution rights to Solesta in June 2009. In December 2011 Salix Pharmaceuticals, Ltd. acquired all of the outstanding stock of Oceana Therapeutics, Inc.
Medical and Research News
NIH Holds Workshop on Clinical Research Agenda for Fecal Incontinence
The National Institutes of Health (NIH) held a workshop August 19–20, 2013 to answer questions about research in fecal incontinence. Despite its serious effects on patients, families, and society, fecal incontinence is often ignored and has been studied less than many other conditions. It has been difficult to identify persons at risk for, or affected by, fecal incontinence because the condition is often not reported or diagnosed. Prevention of fecal incontinence has been hindered by limited research and incomplete knowledge about the biological causes and interacting social and environmental factors.
The workshop included a panel of experts in epidemiology, gastrointestinal physiology, gastroenterology, colorectal surgery, urogynecology, psychology, and behavioral medicine. During the workshop, they identified and discussed major issues in the diagnoses and treatment of fecal incontinence. In addition, the panel examined the barriers encountered in addressing fecal incontinence. Furthermore, the panel was charged to develop research priorities in both basic and clinical research to further advance treatment strategies for fecal incontinence.
New Guidelines for the Diagnosis and Treatment of Achalasia
On July 23, 2013 the American College of Gastroenterology published new guidelines for the diagnosis and treatment of achalasia. Achalasia is a motility disorder in which the esophagus (food tube) empties slowly. The new guidelines for proper diagnosis include several test methods as appropriate when achalasia is suspected. Manometric tests, which show irregular muscle contractions (peristalsis) and incomplete opening of the lower esophageal sphincter, will help confirm the diagnosis so that patients can receive correct treatment tailored to their preferences and the expertise of their care provider.
Eluxadoline Shows Promise in IBS-D
Results published in the medical journal Gastroenterology of a phase 2 clinical trial of a new treatment for IBS-D has shown promising results. The treatment, eluxadoline, is a mu opioid receptor agonist and delta opioid receptor antagonist. The results indicated that eluxadoline helped both decrease abdominal pain and improve stool consistency, as well as improving study subjects’ self-reported quality of life. Phase 3 trials are concluding and results from those trials should be published sometime in the future.
FDA Defines “Gluten-Free” for Food Labeling
On August 2, 2013 the U.S. Food and Drug Administration (FDA) published a new regulation defining the term “gluten-free” for voluntary food labeling. The definition standardizes the meaning of “gluten-free” claims across the food industry including a requirement that the food must contain less than 20 parts per million of gluten. Foods with the claims “no gluten,” “free of gluten,” and “without gluten” must meet the definition for “gluten-free.” While many foods currently labeled as “gluten-free” may be able to meet the new federal definition already, food manufacturers will have a year to bring their labels into compliance with the new requirements.
Study Looks at Liquid and Fiber Intake in Constipation
Researchers at the University of North Carolina at Chapel Hill published a review study looking at the association between a low-fiber diet and liquid intake in adults with constipation. Researchers reviewed data on over 10,000 adults collected by surveys between 2005 and 2008. They reviewed dietary data on these subjects and found that low liquid intake increased the odds of having constipation. The researchers conclude that this may support treating constipation by increasing fluids but note that their study had some methodological limitations, and more evidence is needed.