Celltech Group plc's partner, Bristol-Myers Squibb Co., has decided against further development of a high-risk product in non-small-cell lung cancer following disappointing interim analysis of a Phase II study.
The product is a selective matrix metalloproteinase inhibitor referred to by the companies as BMS-275291.
On Monday Celltech released news saying the Drug Safety Monitoring Committee reported that BMS-275291 was not likely to meet its predetermined efficacy endpoint. The candidate, developed by Celltech, of Slough, UK, was being evaluated in combination with Taxol (paclitaxel) and Paraplatin (carboplatin). Celltech had licensed the candidate to BMS.
Of the failure, Richard Bungay, Celltech's director of corporate communications, told BioWorld Today, "At the outset this was certainly high risk. I think it was a worthwhile trial, but because it was high risk the financial market did not put huge probability on it."
He added that matrix metalloproteinase inhibitors have been associated with many failures.
"There have been problems with side effects from the drugs and there's not one yet that demonstrated good efficacy," he said. "Certainly there weren't high expectations for it. I think if it had worked, it would have been a very nice upside."
Nevertheless, the companies haven't thrown the candidate into the trash. Several small studies in hormone-refractory prostate cancer and Kaposi's sarcoma are ongoing.
Quick Reward On Oxford GlycoSciences Purchase
Celltech's purchase of Oxford GlycoSciences plc, of Oxford, UK, is already beginning to pay off. The company received marketing approval in Israel for Zavesca (miglustat), the first oral treatment for patients with mild to moderate Type I Gaucher's disease for whom enzyme replacement therapy is unsuitable.
Gaucher's is a glycolipid storage disorder in which an enzyme deficiency leads to the accumulation of unmetabolized lipids. Zavesca works by inhibiting glucosyltransferase, a key enzyme involved in the production of glycolipids, thus cutting the rate of glycolipid synthesis.
The approval in Israel is key because the market is second only to the U.S., Bungay said. Citing insufficient evidence to claims that Zavesca (then Vevesca) was safe and efficacious, the FDA rejected the application last summer. In March, OGS filed an amendment to its NDA. (See BioWorld Today, June 25, 2002.)
Bungay wouldn't provide an anticipated timeline on Zavesca's approval in the U.S., saying, "We have a policy of never trying to second guess the FDA."
Zavesca was approved in November in the European Union for patients with mild to moderate Type I Gaucher's disease for whom enzyme replacement therapy is unsuitable.
Celltech and OGS began merging about two months ago. In total Celltech will pay about $173 million for the company, Bungay said. To date, Celltech owns about 90 percent of OGS. Bungay said Celltech expects to gain the remaining 10 percent of the company over the next month or so. (See BioWorld Today, April 14, 2003.)
Seeking Partners For Its Own Pipeline
Celltech is looking for partners in its oncology program that includes CDP 791, a high-affinity PEGylated antibody fragment targeting the VEGF (vascular endothelial growth factor) pathway, and CDP 860, an anti-PDGF-beta receptor PEGylated antibody fragment.
CDP 791 will enter Phase I studies this month. Recent data from a clinical trial in colorectal cancer with an anti-VEGF antibody demonstrated the potential for the class of drugs as adjunctive agents to be used with chemotherapeutic regimens, Celltech said in a prepared statement.
CDP 860 recently competed a small Phase II proof-of-concept study to determine whether it is able to increase the permeability of tumors, which might facilitate an increased uptake of chemotherapeutic agents thereby increasing their effectiveness. Colorectal and ovarian cancer patients were evaluated in the study.
Bungay said the company has not said which types of cancers the products will target.
Celltech also is working with Wyeth Pharmaceuticals, of Madison, N.J., on CMC 544, an antibody-calicheamicin conjugate, in non-Hodgkin's lymphoma.
In other indications, Celltech and Cambridge, Mass.-based Biogen Inc. are developing a Phase III product, CDP 571, an anti-TNF-alpha antibody, in Crohn's Disease. Celltech is working with Peapack, N.J.-based Pharmacia Corp. on CDP 870, an anti-TNF-alpha antibody fragment for rheumatoid arthritis.
Celltech's stock (NYSE:CLL) fell 27 cents Monday to close at $11.63.