British Biotech plc initiated Phase III pivotal trials of its matrixmetalloproteinase inhibitor (MMP), batimastat, for cancerindications. The Oxford, England, company said it is the first MMPto reach that development stage.
British Biotech also said Tuesday that it is taking an orally availableMMP, BB-2516, into Phase I testing. It is a different compound thanbatimastat, which is designed for injection into the peritoneal orpleural cavity.
The Phase III batimastat trials will enroll 150 patients in each of twomulti-center European trials in patients with malignant ascites, acomplication of late-stage ovarian and other abdominal cancers.
The U.K. portion of the study will compare batimastat treatmentfollowing abdominal fluid drainage in 100 patients with a 50-patientcontrol group, which will receive only drainage and a diuretic. Bothgroups will be followed for 84 days. That trial is under way.
The Continental European trial, scheduled to start in the first quarterof 1995, will compare two doses of batimastat with alternativetreatments for malignant ascites, including intraperitonealchemotherapy. Randomized treatment groups of 50 each will receiveeither 1,000 mg/m2 or 500 mg/m2 of batimastat with a second, equaldose administered on reaccumulation; or no treatment other thanchemotherapy or a diuretic.
"The start of pivotal Phase III trials means we consider the bulk ofthe risk in this product to have disappeared," Keith McCullagh, thecompany's CEO, told BioWorld. "We're now 90 percent confidentbatimastat will reach the market and be an effective treatment formalignant ascites and pleural effusions."
Two U.K. Phase II studies of batimastat have been conducted. In amalignant ascites study, reported on in March, 12 of 23 patients didnot need drainage of their ascites. A second study begun in Mayincluded 40 patients. Both trials showed the drug was well toleratedand had an apparent effect on reaccumulation of ascites.
Peter McCann, president of the company's Annapolis, Md.-basedU.S. subsidiary, British Biotech Inc., told BioWorld that it "is verylikely we may be having a primary effect on the tumor cellsthemselves. But what we're shooting for [now] is a simple, directendpoint: Do we have an effect on malignant ascites, and do we havea way to quantify that effect?"
He said the drug is not specifically designed to kill tumor cells butrather to block the growth or spread of tumor cells in tissues.
"It's been shown that this class of enzymes is very much involved inthe movement and spread of tumor cells," McCann said. "So theseinhibitors were specifically designed with that in mind. Perhaps youcan have a significant effect on the tumor cells without killing them."
McCullagh said, "Having done the Phase II trials in Europe, we thinkwe can go straight to larger-scale pivotal trials in the U.S. We havehad a number of discussions with the FDA and we feel reasonablyconfident they will agree to that."
There is an ongoing Phase I/II U.S. trial studying batimastat invarious cancers. McCann said two Phase II studies are expected tostart in the U.S. by early in 1995. British Biotech intends to apply forEuropean marketing approval by the first quarter of 1996, he said.
"Not only is [batimastat] a drug in its own right, it acts as proof ofprinciple for other drugs of the same class," McCullagh said. "If wethink batimastat has significant market potential, BB-2516 issubstantially larger. It's potentially a major drug in thepharmaceutical industry."
He said the oral molecule has broader applications in addition to itsadvantages in administration. "We're keen to move that quickly intoPhase II testing," McCullagh said, adding that four Phase II U.S.studies of BB-2516 are planned for the U.S. in 1995 in variouscancers, possibly ovarian, prostate, colorectal and lung.
Two weeks ago British Biotech reported that it was going into PhaseI/II trials in nine cancer patients in the U.K. with its Stem CellChemokine, BB-10010, which is being tested for its ability tomobilize blood cells into peripheral blood and as a protector of stemcells during chemotherapy. n
-- Jim Shrine
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