Berlex Laboratories Inc. is taking a long-approved cancer drug into late-stage development for another indication.

The Montville, N.J.-based company said it would begin a Phase III study of Leukine (sargramostim) for Crohn's disease. The product, a hematopoietic growth factor that stimulates neutrophils, monocyte/macrophages and dendritic cells, received its first approval in 1991 to reduce infections by boosting white blood cells in acute myelogenous leukemia patients following induction chemotherapy.

Berlex said it remains in discussions with the FDA relative to the trial's design and endpoints. But it expects to begin patient enrollment by the end of the year.

The company has marketed the drug in the U.S. since last summer, when it was acquired by Schering AG, of which Berlex is an affiliate. The Berlin-based business paid about $380 million in cash to buy Leukine from Immunex Corp., under whose stewardship it received FDA approvals for four additional indications related to bone marrow and peripheral blood stem cell transplantation. (See BioWorld Today, May 6, 2002.)

The deal also included two milestone payments to the Seattle-based company related to further development in Crohn's disease as well as reaching an undisclosed sales target. Immunex was looking to shed the asset as part of its acquisition by Thousand Oaks, Calif.-based Amgen Inc., which already marketed the cancer drug Neupogen (filgrastim). (See BioWorld Today, Dec. 18, 2001.)

The drug's use in Crohn's patients originated outside of Immunex, though.

"Some investigators at Washington University were using Leukine in some other studies of patients with immune disorders," Kimberley Jordan, Berlex's manager of public relations, told BioWorld Today. "The patients had Crohn's-type systems, and they found that when they administered Leukine to these patients, the Crohn's symptoms resolved. So they came up with the hypothesis that it might be useful to try Leukine as a treatment directly for Crohn's."

Data from an eight-week pilot study conducted at the St. Louis school, published in the November 2002 issue of The Lancet, showed that 12 of 15 Crohn's patients responded to Leukine treatment. Eight achieved clinical remission.

The Phase II program, which Berlex inherited from Immunex, began soon after. Berlex declined to provide specific findings from the 124-patient, multicenter, randomized, double-blinded, placebo-controlled study, though it expects to provide such data in upcoming peer-reviewed publications and scientific meetings.

"The mechanism of action hasn't exactly been determined, but the study explored the hypothesis that Crohn's disease results from a defect in innate immunity," Jordan said. "So by stimulating the growth of these hematopoietic cells, then it may be of benefit for these patients. Many of the other treatments focus on immunosuppression, so this would be a novel approach at stimulating the innate immune system."

But the positive findings fit into Berlex's justification for buying the drug.

"A good portion of the acquisition price was allocated to Crohn's," Joanne Marion, the director of investor relations for Schering in the U.S. and Canada, told BioWorld Today. "It was important as an oncology drug, because we had an oncology portfolio and a sales force we could leverage. Leukine certainly is a good oncology product. But moving into the future, we were looking at the Crohn's indication."

In 2001, Leukine sales reached $108 million under Immunex. Marion said its sales figures for the first six months of this year reached about $29 million, a lower half-year amount resulting from Berlex's transition phase and newfound competition from Neulasta (pegfilgrastim, from Amgen). She said the sales figures picked up during the second quarter, though, and eventually could settle between $75 million and $100 million for the whole year but remain south of Immunex's peak sales.

Marion added that the addition of the Crohn's indication conservatively could add $272 million in annual sales. Jordan said Berlex would consider additional indications for Leukine, though she declined to provide specifics.

Beyond Leukine's development, Berlex's therapeutic pipeline also includes a VEGF kinase inhibitor in Phase III studies for colon cancer. The anti-angiogenesis product is partnered with Novartis AG, of Basel, Switzerland.

Another partnered product, Zevalin, is under European regulatory review as a treatment for non-Hodgkin's lymphoma. It is marketed in the U.S. by IDEC Pharmaceuticals Corp., of San Diego.

Berlex owns all rights to another late-stage product, a gene therapy for myocardial ischemia in Phase IIb/III development as a bio-bypass.

The company also develops products for reproductive health care, dermatology and diagnostic imaging.