Schering AG, Germany (BERLIN, Germany), announced results from two recently completed multicenter, placebo-controlled, randomized, double-blind clinical studies of sargramostim for the treatment of Crohn's disease. Results from the phase III induction trial suggest a treatment benefit but fail to demonstrate superiority in the two primary end points of response and/or remission at 8 weeks compared with placebo. However, primary and secondary end points were met in a phase II trial in which sargramostim was demonstrated to be significantly more effective than placebo for induction of corticosteroid-free clinical remission in patients with steroid-dependent Crohn's disease.

The phase III study was conducted in nine countries and was designed to evaluate the induction of response and remission in 288 patients with moderately to severely active Crohn's disease. Patients received 6 μg/kg/day sargramostim or placebo via subcutaneous injection for 8 weeks. Efficacy was based on the Crohn's Disease Activity Index (CDAI), the standard measure of treatment effectiveness based on an analysis of several variables assessed by patients and physicians. Response was defined as a CDAI decrease of at least 100 points and remission was defined as a CDAI score of 150 points or below. The results in this study were achieved without the use of steroids and/or immunosuppressants.

The phase II study was conducted in the US and Canada in 129 patients with active corticosteroid-dependent Crohn's disease requiring 10–40 mg of prednisone or equivalent. Patients received 6 μg/kg/day sargramostim or placebo via subcutaneous injection. Treatment duration was between 12 and 22 weeks depending on baseline corticosteroid dose. The primary efficacy end point was corticosteroid-free clinical remission (CDAI <e;150) 4 weeks after complete corticosteroid withdrawal.

According to Professor Marc Rubin, member of the Executive Board of Schering AG, responsible for Development and Specialized Therapeutics, the phase II study "is the first randomized, double-blind, placebo-controlled trial conducted with any biological therapy in active steroid-dependent Crohn's disease patients." Rubin stated that the development program continues to move forward and that Schering AG is conducting an in-depth analysis of the data and will be in contact with regulatory agencies to discuss any potential adjustments to the development program to obtain regulatory approval.

In the US, sargramostim is marketed as LEUKINE^R by Berlex, Inc, a US affiliate of Schering AG, Germany, and has been administered to more than 300,000 patients, most of whom are suffering from acute myelogenous leukemia (AML). Leukine is a recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF). GM-CSF is a hematopoietic growth factor that stimulates proliferation and differentiation of hematopoietic progenitor cells. The amino acid sequence of Leukine differs from that of natural human GM-CSF by a substitution of leucine at position 23, and the carbohydrate moiety may be different from that of the native protein.

—A. Techman

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