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New Medications in the Pipeline Promising Treatment for Short Bowel Syndrome
The Annals of Surgery has published the findings of a phase III trial of Zorbtive™. This trial tested the effects of Zorbtive combined with a specialized oral diet and glutamine (an amino acid) on the need for intravenous nutritional support (parenteral nutrition, or PN) in patients with short bowel syndrome. Zorbtive is a genetically engineered human growth hormone manufactured by Serono, Inc., a biotechnology company headquartered in Geneva, Switzerland.
Short bowel syndrome is a rare but serious condition that can result from the surgical removal of a significant portion of a person's small intestine. For people with the syndrome, the body is unable to adequately absorb water, vital nutrients, and electrolytes – important minerals that regulate many metabolic processes. These patients often need long term PN to replace lost fluids and nutrients.
Zorbtive [somatropin (rDNA origin) for injection] is the only therapy approved by the FDA for short bowel syndrome, to be used specifically in patients dependent on PN. It is thought to work by improving the adaptation of the remaining small bowel following surgery. This adaptation begins after surgery and continues for 2-3 years. In the new clinical study, Sereno has been testing Zorbtive plus diet and glutamine to see whether the combination would actually reduce patients' PN requirements as measured by volume, calories, and frequency of infusion. The study compared the effects of specialized diet and glutamine, specialized diet and Zorbtive, and specialized diet, glutamine and Zorbtive.
Results: All groups benefited, but patients taking Zorbtive combined with glutamine and diet had the greatest reduction in PN requirements, decreasing the frequency of PN infusions from 5-6 days weekly to 1-2 days weekly.
For more information about Zorbtive, please visit http://www.zorbtive.com/.
Adalimumab (Humira®) and Certolizumab Pegol (Cimzia™) for Crohn's Show Promise in Phase III Trials, Early Rifaximin Trials in IBD Merit AttentionAdalimumab (Humira®) and Certolizumab Pegol (Cimzia™), both anti-TNF therapies, have shown promising results for the treatment of Crohn's disease, according to their respective Phase III clinical trials. The studies' results were recently presented at the 2005 American College of Gastroenterology (ACG) meeting in Honolulu.
Adalimumab (Humira®)
The first leg of the recently concluded Phase III adalimumab study was CLASSIC I -- a four-week, randomized, double-blind, placebo-controlled trial to determine the efficacy and safety of adalimumab for inducing clinical remission in patients with moderate-to-severe Crohn's disease. Here, clinical remission is defined as having a Crohn's Disease Activity Index (CDAI) of less than 150. (Patients with moderate-to-severe disease generally have a CDAI between 220 and 450.)
CDAI is a composite score of eight factors used to assess a patient's wellness, including the daily number of liquid or very soft stools, severity of abdominal pain, level of general well-being, and other measures.
At the conclusion of CLASSIC I, patients became eligible to enroll in CLASSIC II, the extension study designed to evaluate the drug's ability to maintain clinical remission. Depending on their remission status at weeks zero and four of the earlier trial, patients were assigned to one of two groups:
- a randomized group, in which participants were equally likely to receive 40 mg of adalimumab every week, 40 mg of adalimumab every other week, or placebo; and
- an open-label group, in which patients received the standard dose of 40 mg of adalimumab every other week.
Fifty-five patients were assigned to the randomized group. At the end of one year, 83% of those taking adalimumab every week maintained clinical remission versus 44% for placebo. Of patients taking the drug every other week, 74% maintained remission versus 44% for placebo.
The remaining 221 patients -- those who were not in clinical remission at weeks zero and four of the CLASSIC I study -- were assigned to an open-label group. At the end of one year, 43% achieved clinical remission, while 69% showed a clinical response, with a decline in CDAI of at least 70 points, and 61% achieved a decline of at least 100 points.
Manufactured by Abbott Laboratories, adalimumab is an approved treatment for rheumatoid arthritis and psoriatic arthritis. For more information, please visit http://www.humira.com/.
Certolizumab Pegol (Cimzia™)
According to the results of a Phase III study of certolizumab pegol, a single 400 mg injection of the drug every four weeks was effective in maintaining remission of Crohn's disease, following treatment with the drug to induce remission.
Like the Phase III adalimumab trial, the certolizumab study, titled PRECiSE 2, had two legs. The first leg was designed to evaluate the drug's ability to induce remission in 668 patients with Crohn's disease. At the end of six weeks, 64% of that group -- those who responded to certolizumab as measured by their CDAI -- went on to participate in the remaining leg of the study, which focused on drug's ability to maintain remission.
Study Highlights
- 62.8% of patients receiving certolizumab maintenance therapy sustained an overall clinical response throughout the 26-week study period, compared to 36.2% with placebo. Clinical response was defined as a 100 point drop in the CDAI.
- 47.9% of patients receiving maintenance therapy with certolizumab were in clinical remission (CDAI less than or equal to 150 points) at week 26, compared to 28.8% with placebo.
- Adverse events were mostly mild to moderate, with headache being the most common. Serious non-Crohn's-related infections were observed in both the certolizumab and placebo groups.
The PRECiSE clinical trial program is composed of four studies. Still underway, PRECiSE 3 and 4 are open-label trials for patients who participated in either PRECiSE 1 or 2, designed to assess the longer-term safety and tolerability of certolizumab.
Certolizumab is manufactured by UCB Pharmaceuticals, Inc. The company plans to file regulatory submissions for the treatment of Crohn's disease in the United States and Europe in 2006.
To find a clinical trial in your area, please visit the clinical trials section of our site.
Rifaximin (XIFAXAN™), an oral antibiotic currently approved for travelers' diarrhea, may be effective in treating severe Crohn's disease, according to a recent study published in Current Medical Research and Opinion.
At the end of treatment with rifaximin, 78% of the 29 adult patients participating in this 16-week study underwent significant improvement as measured by their Crohn's Disease Activity Index (CDAI), and 59% achieved total remission. These results bolster the theory that Crohn's disease is driven by an abnormal response to the bacteria in the intestinal tract, says Ira Shafran, M.D., the study's principal investigator. By reducing the absolute number of bacteria in the intestine, the drug may be reducing the number of environmental triggers that provoke that abnormal immune response.
Rifaximin, which is manufactured by Salix Pharmaceuticals, Ltd., is a non-systemic, gut-selective antibiotic. In other words, instead of being absorbed into the bloodstream, rifaximin targets problems specific to the gastrointestinal (GI) tract. That makes it potentially suitable as a treatment for Crohn's, the study's authors believe.
Taking Off in Pilot Studies
An open-label study is one in which both health providers and patients are aware of the drug or treatment being given. A pilot study is a mini-version of a full-scale trial, and an essential first step in successful study design. In the past year, several open-label pilot studies of rifaximin have suggested the drug's potential in treating IBD by attacking specific bacteria in the gut.
In one such study, rifaximin proved effective in the treatment of small bowel bacterial overgrowth (SBBO) -- a syndrome that involves excessive bacteria growing in the small intestine. Large numbers of bacteria compete with the person who has the condition -- the "host" -- over nutrients. As a result, people with SBBO may lose precious nutrients, with serious consequences for their health. SBBO can occur with Crohn's disease, scleroderma, and intestinal strictures, among other conditions.
The antibiotic also performed well in several other pilot studies, including a small trial in patients with mild-to-moderate Crohn's disease. The drug's benefits were most pronounced in patients with disease affecting their colon, but improvements were observed in those with small-bowel disease as well.
Finally, the results of a study of rifaximin for pouchitis -- inflammation of the internal pouch created after surgical removal of the colon -- point to the drug's potential as a treatment for that condition. Pouchitis affects more than 30% of those who have undergone the surgery.
Further Investigation Warranted
Salix intends to sponsor further studies to evaluate the use of rifaximin in the treatment and maintenance of remission in Crohn's disease, including a post-surgical study. The researchers agree that the data gathered in the above-mentioned pilot studies, while promising, merit further evaluation in randomized, placebo-controlled trials.
Date Posted: December 20, 2005
Date Updated: January 26, 2006
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