British Biotech plc put a Phase III pivotal trial of batimastat on holdbecause of side effects attributed to a new manufacturing process, theOxford, England, company said Friday.
U.K. trials of the metalloproteinase inhibitor (MMP) for malignantascites, a form of late-stage abdominal cancer, are expected toresume in June, when British Biotech gets regulatory approval to useproduct from its original manufacturing method. A separateEuropean study, which also was to include 150 patients for the sameindication, had not begun and also will be delayed, said KeithMcCullagh, the company's chief executive.
"Nothing we announced affects the potential of the product nor itsmarket size," McCullagh told BioWorld. "We still think it will be asuccessful treatment for late-stage cancer. We've simply had asetback in timing."
Trials of batimastat continue in malignant pleural effusions, a cancerof the chest cavity. Studies also are going forward with BB-2516, anorally available MMP expected to have broader applications thanbatimastat.
Shares in British Biotech fell 99 pence, or 17 percent, to close at 491pence on the London Stock Exchange Friday. In Americandepository receipts (NASDAQ:BBIOY), British Biotech lost $2.50Friday, closing at $14.50.
The company, when it started the Phase III trials in November (seeBioWorld Today, Nov. 16, 1994, p. 1), said it expected to file forEuropean marketing approval in the first quarter of 1996.
The U.K. trial was designed to enroll 150 patients, comparing 100patients treated with batimastat following abdominal fluid drainagewith a 50-patient control group, which was to receive only drainageand a diuretic. The trial was stopped after recruitment of 16 patients,11 of whom were in the treatment arm, McCullagh said.
"Two-thirds of the patients receiving the active drug had pain anddiscomfort, which was severe and in some cases lasted several days,"he said. "That was quite different than anything we had seen inprevious studies. We knew there was something different, and theonly change we made was in the last stage of the manufacturingprocess. It was quite easy to track down."
In going from Phase II to Phase III trials, the company scaled up itsmanufacturing procedure. One of the changes _ changing fromwater to an organic solvent in the manufacturing's last step _ wasintended to result in a more pure product. Instead, McCullagh said, itcaused the unexpected side effects.
The studies of batimastat in pleural effusions were unaffectedbecause the drug was being provided from the earlier batch.McCullagh said parallel Phase II studies for that indication areexpected to start in U.S. and U.K. in the next few months.
The orally active MMP inhibitor, BB-2516, has finished a single-dose Phase I study and is going into a study involving seven days ofcontinuous dosing. Results, as well as plans for continueddevelopment, will be presented March 21 at the AmericanAssociation for Cancer Research conference in Toronto.
McCullagh said the plan is to take BB-2516 into small-scale Phase IIstudies in colorectal, pancreatic, lung, prostate and other cancers."We'll be scaling up a whole series of cancer trials through the yearon both sides of the Atlantic," he said.
The success of BB-2516 and its expected oral availability means thatit will replace batimastat as the company's lead drug for solidcancers, McCullagh said. "We have consigned the use of batimastatto the two indications: pleural effusions and malignant ascites," ortumors involving fluid accumulations.
In a Phase II U.K. study of batimastat for malignant ascites, 12 of 23patients did not need drainage of their ascites. In that trial andanother, the drug was well tolerated and had an apparent effect onreaccumulation of ascites. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.