Digestive Health Matters Vol. 22 No. 1
- Understanding Bloating and Distension
- Highlights from the 10th International Symposium on Functional Gastrointestinal Disorders
- IFFGD Presents the 2013 Research Awards
Here are summaries of some recent news about research and treatments for digestive health.
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 is a capsule taken once daily on an empty stomach, at least 30 minutes before the first meal of the day. Linzess helps relieve constipation by helping bowel movements occur more often. In IBS-C, it may also help ease abdominal pain.
Linzess should not be used in patients 16 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.
Ironwood and Forest are co-producing linaclotide in the U.S. 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.
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.
In May 2013, Ferring Pharmaceuticals announced 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.
FDA Approves Lubiprostone to Treat Opioid-Induced Constipation; Drug Already Used to Treat Other Constipation Disorders
On April 23, 2013 Sucampo Pharmaceuticals, Inc. and Takeda Pharmaceuticals U.S.A. Inc. announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental New Drug Application for lubiprostone (Amitiza) to treat opioid-induced constipation in adult patients with chronic non-cancer pain.
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.
Lubiprostone was approved by the FDA to treat chronic idiopathic constipation (CIC) in adults in 2006 and to treat IBS with constipation (IBS-C) in adult women in 2008.
Amitiza (lubiprostone) 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.
Solesta has been approved to treat fecal incontinence in the U.S. since 2011 and in Europe since 2006. The drug, 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).
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 or 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.
Teduglutide Studied over 52-Week Treatment Period; Approved in the U.S. to Treat Short Bowel Syndrome
In January 2013, an international multi-center study involving 52 patients looked at the safety, tolerability, and efficacy of teduglutide (Gattex) 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 glucagonlike peptide 2).
The most common adverse events reported included headache, nausea, and abdominal pain. Of seven patients who withdrew because of adverse events, four were considered treatment related. 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.
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.
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.
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.
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
Probiotics are live microbiologic organisms, found in foods and supplements, that have natural health benefits. The beneficial properties inherent to each probiotic species are strain specific.
Two randomized, controlled trials have validated the effectiveness of Bifidobacterium infantis (B. infantis) 35624, a probiotic that has the unique ability to reduce intestinal inflammation, for treating both individual and global IBS symptoms without evidence to suggest an increase in adverse events. The studies reported that the strain appears safe and effective for the treatment of IBS. Increasing data has revealed that changes in inflammation within the gut may play a role in the development of the digestive disorder. A review of the two trials was published in the Volume 104 of The American Journal of Gastroenterology in April 2009.
Bifidobacterium infantis 35624, trademarked under the name bifantis, is the natural probiotic strain found only in Align, a supplement from The Procter and Gamble Company.
Gastric electrical stimulation (GES) uses a surgically implanted battery operated device on the stomach to try to help control symptoms of nausea and vomiting in gastroparesis when other methods have failed. The Enterra therapy is approved by the U.S. Food and Drug Administration (FDA) as a Humanitarian Device Exemption. The Enterra Therapy System is manufactured by Medtronic, Inc.
A study reported in the April 2013 issue of the Journal of Gastrointestinal Surgery looked back at the records of 233 patients who had a GES implanted at a single institution between 2000 and 2011. The investigators found that while most patients reported improvement of gastroparesis symptoms after GES implantation, there is often a need for additional surgical procedures and occurrence of related complications. Improved understanding leads to practice changes aimed at reducing the rate of complications and additional procedures.
A study reported in the April 2011 issue of the journal Clinical Gastroenterology and Hepatology assessed the long-term clinical outcomes of GES therapy. Investigators looked back at records for a period of one to 11 years (4.5 years mean) of 221 patients with severe gastroparesis that were treated with Enterra Therapy System. The reviewers observed significant improvement in symptom scores and reduced medication use in 48% to 53% of patients. Weight increased significantly and in 89% J-tubes could be removed. The therapy was found generally safe and well tolerated, with improvement sustained for up to 10 years. Medtronic partially funded this study.
Medical and Research News
In early June 2013 Astellas Pharma and Zeria Pharmaceutical announced the launch of Acofide (acotiamide hydrochloride hydrate) for the treatment of functional dyspepsia in Japan. This will be the first approved treatment in a new drug class which has demonstrated effectiveness for functional dyspepsia.
Functional dyspepsia is characterized by chronic or recurrent pain or discomfort centered in the upper abdomen. Though symptom overlap is common among some functional gastrointestinal disorders (FGIDs), it is important not to confuse functional dyspepsia with other common FGIDs like IBS and GERD.
Functional dyspepsia is identified based on symptoms. Additional evaluation by your physician will normally include a physical exam to rule out other possible causes. The actual diagnosis is based on a detailed history to identify symptoms.
In late March 2013, The U.S. Food and Drug Administration (FDA) announced the approval of the proton-pump inhibitor (PPI) Aciphex Sprinkle for treatment of GERD in children ages 1 to 11 years.
Approval of the treatment is based on the results of a multicenter, double-blind, parallel-group clinical trial in children. The study looked at 127 children with GERD confirmed by endoscopy. Overall, 81 percent of children achieved healing during the 12-week treatment period.
The most commonly reported side effects during treatment were cough (14%), vomiting (14%), abdominal pain (12%), diarrhea (11%), fever (10%), headache (9%), upper respiratory tract infection (8%), sore throat (6%), and inflammation of the nasal passages and pharynx (5%).
GERD, or gastroesophageal reflux disease, is very common. It develops when the back-flow (reflux) of stomach contents causes troublesome symptoms and/or complications. Serious health problems can result if it is not treated properly.
On April 11, 2013 the U.S. Food and Drug Administration (FDA) announced that three functional gastrointestinal and motility disorders were selected as disease areas to be addressed during the first three years of its Patient-Focused Drug Development. Those conditions are IBS, gastroparesis, and gastroesophageal reflux disease (GERD) with persistent regurgitation symptoms on proton pump inhibitors.
Patient-Focused Drug Development is a five-year initiative, which calls for the FDA to obtain patients’ perspectives on specific disease areas, including thoughts on their conditions and available therapies, as well as the impact the conditions have on their daily lives. These perspectives can play a role in developing new drug therapies and provide key knowledge to the FDA as it reviews applications for new drugs in certain disease areas.
The FDA considered comments from patients, caregivers, advocate groups, health care professionals, pharmaceutical companies, and others as they determined the list of disease areas to be addressed during the first three years of Patient-Focused Drug Development.
In October 2012, DHA and IFFGD invited advocates to submit comments to the FDA as they considered which disease areas to be included. We thank all those that participated for their support and activism. The FDA will initiate a second public process to determine the disease areas for consideration for upcoming years of the initiative (a total of 20 areas will be included over the five year period). IFFGD and DHA will share the opportunity with our advocates when it becomes available.
In addition to public comments, the FDA used the following criteria when selecting the initial 16 disease areas to be considered as part of Patient-Focused Drug Development:
- Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
- Disease areas for which aspects of the disease are not formally captured in clinical trials; and
- Disease areas for which there are currently no therapies or very few therapies, or the available therapies to not directly affect how the patient feels or functions.
Patient-Focused Drug Development is part of the Prescription Drug User Fee Act (PDUFA). PDUFA V is the fifth authorization of the act that gives the FDA the ability to collect fees from companies that produce certain human drug and biologic products. These fees then provide the FDA with the resources necessary to maintain and improve the drug review and approval process.
The FDA’s full announcement of the disease areas to be addressed in fiscal years 2013–2014, including the full list of disease areas, can be viewed in the Federal Register at http://www.gpo.gov/fdsys/pkg/FR-2013-04-11/pdf/2013-08441.pdf
- Now accepting applications for IFFGD's 2013 Idiopathic Gastroparesis research grants
- ANMS Annual Meeting 2013: September 20-22, 2013 in Huntington Beach, CA
- World Congress of Gastroenterology (Gastro 2013): September 21-24, 2013 in Shanghai, China
- The 15th Annual Celiac Disease Symposium: September 22-25, 2013 in Chicago, IL
- NASPGHAN 2013 Annual Meeting & Postgraduate Course: October 10-12, 2013 in Chicago, IL
- ACG Annual Scientific Meeting and Postgraduate Course: October 11-16, 2013 in San Diego, CA
- United European Gastroenterology Week (UEGW): October 12-16, 2013 in Berlin, Germany