Berlex Laboratories Announces Results From Randomized, Placebo-Controlled Study Of Leukine(R) For Crohn's Disease
Tuesday October 14, 4:12 am ET
MONTVILLE, N.J., Oct. 14 /PRNewswire-FirstCall/-- Berlex Laboratories, a U.S. affiliate of Schering AG, Germany (NYSE: SHR, FSE: SCH), announced new data from a Phase II clinical trial showing that patients receiving LEUKINE® (sargramostim) for the treatment of moderately to severely active Crohn's disease had significantly greater clinical response and remission rates than those receiving placebo. The Phase II data from a multi-center, randomized, double-blind, placebo-controlled study will be presented today at the 68th Annual Scientific Meeting of the American College of Gastroenterology (ACG).
"The most promising aspect of these results is they suggest LEUKINE may offer a unique approach to treatment for Crohn's disease that, unlike many current Crohn's disease treatments, does not involve immunosuppressive therapy," said Brian K. Dieckgraefe, M.D., Ph.D., co-investigator and assistant professor of medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Mo.
In the Phase II trial, nearly half of patients treated with LEUKINE (48%) had a decrease of CDAI of more than 100 points, and more than one-third of patients (40%) achieved clinical remission by the end of the study (CDAI less than or equal to 150), versus 26% and 19% of the placebo-treated patients, respectively (p=0.013 and p=0.014, respectively). More than half of patients treated with LEUKINE (54%) achieved a CDAI decrease of more than 70 points, versus 44% of placebo-treated patients (p=0.275). These results were achieved without the use of steroids and/or immunosuppressants.
Additionally, significant differences between LEUKINE and placebo were observed in the length of time to response and time to remission.
Disease severity was measured using the Crohn's Disease Activity Index (CDAI), the standard measure of treatment effectiveness. A CDAI score is based on an analysis of several variables assessed by patients and physicians. A lower CDAI score correlates with less severe disease activity.
The Phase II study was initiated following positive results in an earlier Washington University pilot trial. This pilot trial was based on the hypothesis that, rather than being the result of an overactive immune system as traditionally believed, Crohn's disease may in fact result from a deficiency in innate immunity. To verify the positive pilot trial results, investigators from Washington University, as well as investigators at 34 additional trial sites across the United States, evaluated 124 patients in the Phase II trial to study the efficacy and safety of LEUKINE, which stimulates the immune system, in the treatment of moderately to severely active Crohn's disease.
"The idea of stimulating the immune system in patients with Crohn's disease seems counter-intuitive to many physicians and patients," said Joshua Korzenik, M.D., co-investigator and assistant professor of medicine, Division of Gastroenterology, Washington University School of Medicine, St. Louis, Mo. "It's gratifying to learn that the Phase II trial results upheld the promise of our pilot study."
The results of this study are very encouraging," said Rodger DeRose, president and CEO of the Crohn's & Colitis Foundation of America (CCFA). "There is no cure for Crohn's disease, and unfortunately, not all patients respond well to conventional therapies. It's exciting to see that potential new treatments like this one are moving forward in development. CCFA is proud to play a role in this effort by listing clinical trials on our web site at www.ccfa.org."
Berlex announced that patient recruitment for a Phase III program of LEUKINE for the treatment of moderately to severely active Crohn's disease is planned to begin early in 2004.
"As a result of our continued commitment to clinical research and development in new and promising areas of LEUKINE use, we are very enthusiastic that LEUKINE solidly achieved the most rigorous endpoints in this trial for Crohn's disease," said Reinhard Franzen, president and chief executive officer, Berlex Laboratories. "We are marketing LEUKINE successfully in the United States in oncology indications and look forward to learning more about the potential of LEUKINE as a new treatment option for Crohn's disease."
About the Phase II Study
The study was initiated in October 2001 and conducted at 35 U.S. centers following positive outcomes from a 15-patient pilot study. The multi-center, randomized, double-blind, placebo-controlled Phase II study evaluated 124 patients to verify efficacy and safety of LEUKINE in the treatment of moderately to severely active Crohn's disease. Patients received LEUKINE or placebo, with no significant differences in baseline characteristics. Median baseline CDAI scores were 300 (LEUKINE, range 219-469) and 300 (placebo, range 221-464).
The pre-defined efficacy endpoints of the trial were a greater than or equal to 70 point decrease in CDAI, a great than or equal to 100 point decrease in CDAI and clinical remission (CDAI less than or equal to 150).
A significantly greater proportion of patients treated with LEUKINE than placebo patients responded (decrease in CDAI greater than or equal to 100, 48% [39/81] vs. 26% [11/43], p=0.013) and achieved clinical remission (CDAI less than or equal to 150, 40% [32/81] vs. 19% [8/43], p=0.014) at the end of study treatment without the use of steroids and immunosuppressants (day 57). A greater proportion of patients treated with LEUKINE achieved a 70-point decrease from baseline CDAI than placebo patients (54% (44/81) vs. 44% (19/43) respectively, p=0.275). The proportion of patients achieving CDAI response (70 and 100 points) and remission were significantly different from placebo at day 29. Differences in median CDAI scores were observed by the first assessment (15 days). Significant differences between the LEUKINE and placebo groups were observed in the time to 100 point response (30 days vs. not reached, p=0.003) and remission (56 days vs. not reached, p=0.004). Quality of life parameters were consistent with the improvement in CDAI score. LEUKINE treatment was generally well-tolerated; most commonly observed adverse events include mild to moderate injection site reactions and bone pain.
"Since this study was initiated, the general gastroenterology community and regulatory agencies have recognized that more stringent criteria are needed to define response to treatment, due to an increase in placebo response rates observed in recent Crohn's disease trials," said Korzenik. "Therefore, it was not unexpected that LEUKINE did not achieve statistical significance versus placebo in reaching the least-stringent trial endpoint of a greater than or equal to 70-point CDAI decrease, which was the primary endpoint.
"The efficacy endpoints of greater than or equal to 100-point decrease in CDAI score as well as clinical remission represent these more rigorous endpoints now being required for new Crohn's treatments. In this study, LEUKINE met both of these more difficult-to-achieve parameters," Korzenik continued.
About Crohn's Disease
Crohn's disease is a chronic and serious inflammatory disease of the gastrointestinal (GI) tract. Crohn's disease affects men and women equally and seems to be more common within families. About 20 percent of people with Crohn's disease have a blood relative, most often a brother or sister, with some form of inflammatory bowel disease (IBD).
Crohn's disease can be difficult to diagnose because its symptoms are similar to other intestinal disorders such as irritable bowel syndrome (IBS) and ulcerative colitis. Crohn's disease causes inflammation in the small intestine; however, it can affect any part of the digestive tract from the mouth to the anus. The inflammation from Crohn's disease can extend deep into the lining of the affected organ, causing pain and frequent bowel movements. Currently there is no cure for Crohn's disease, and many patients rely on steroids and/or immunosuppressive therapies that do not prevent recurrences of the disease.
About LEUKINE
LEUKINE, which Schering AG acquired in July 2002, is a hematopoietic growth factor that stimulates neutrophils, monocyte/macrophages, and dendritic cells. LEUKINE is marketed in the United States by Berlex Laboratories. Since its approval, LEUKINE has been administered to more than 300,000 patients.
LEUKINE was first approved in 1991 and is the only colony-stimulating factor approved for use following induction chemotherapy in older adults with acute myelogenous leukemia (AML) to shorten the time to neutrophil recovery and reduce the incidence of severe and life-threatening infections and infections resulting in death. LEUKINE also has been approved for four additional indications: use in myeloid reconstitution following allogeneic and autologous bone marrow transplantation (BMT), use for peripheral blood stem cell (PBSC) mobilization and subsequent myeloid reconstitution in patients undergoing PBSC transplantation, and use in bone marrow transplantation failure or engraftment delay.
Patients taking LEUKINE may experience some side effects, most of which are mild to moderate. Some common side effects may include bone pain, a slight temperature elevation (usually less than 100.5o F or 38oC) for a short period of time after the injection, and swelling, redness, and/or discomfort around the injection site.
About Berlex
Committed to developing novel diagnostics and therapeutics that address unmet medical needs, Berlex Laboratories develops and markets ethical pharmaceuticals in the areas of Female Healthcare, Diagnostic Imaging, Dermatology, as well as Specialized Therapeutics for life-threatening and disabling diseases in the fields of the central nervous and cardiovascular systems, oncology, and gastroenterology. Berlex has business operations in New Jersey, California and Washington. For more information on currently marketed products, please visit www.berlex.com... |
