By Jim Shrine
Special To BioWorld Today
Intercardia Inc. and Astra Pharmaceuticals LP ended a nearly three-year-old collaboration on the development of Bextra (bucindolol) because of a non-compete clause that came into effect when Astra AB and Merck & Co. restructured their alliance this summer.
All U.S. rights to the beta-blocker, which is nearing the end of a large Phase III study for congestive heart failure, were returned to Intercardia.
"At this point, we will start focusing on discussing Bextra with potential collaborative partners," said Bennett Love, vice president of corporate planning and communications for Intercardia, of Research Triangle Park, N.C.
"We have received some interest, even prior to making the announcement of the final termination," he said. "Due to the nature of the indication, it deserves to have strong marketing support."
In August, Intercardia noted a potential conflict due to the restructuring at Astra Merck Inc., of Wayne, Pa., with whom the original deal was made. In June, the Astra Merck joint venture was combined with Sodertalje, Sweden-based Astra AB's wholly owned subsidiary, Astra USA Inc., into a new limited partnership controlled by Astra. (See BioWorld Today, June 22, 1998, p. 1.)
Astra Pharmaceuticals' beta-blocker, Toprol-XL, also is in late-stage studies for treating heart failure.
As part of the termination, Intercardia received a $4 million payment. When the deal was signed in December 1995, Intercardia got $5 million up front from Astra Merck, and could have realized $15 million more upon approval and achievement of certain sales goals. Intercardia would also have received royalties of 15 percent or 30 percent, depending on sales.
The synthetic small molecule is a non-selective beta-blocker with vasodilating properties. It has been studied since June 1995 in the Beta-blocker Evaluation of Survival Trial (BEST) with a primary endpoint of survival. The study, with more than 2,500 patients enrolled, is being run in conjunction with the National Institutes of Health and the Department of Veteran Affairs.
David Crossen, senior biotechnology analyst at Montgomery Securities, in San Francisco, said the BEST trial is likely to be unblinded in November.
"Signs from the company appear to suggest the trial should be successful," Crossen said. "I'm not assuming Astra is second guessing the trial or that the product won't work, although that's obviously a question mark some people will raise."
Finding a new partner for Bextra "will be easy once the data are out," Crossen added. "It is a potentially huge market. Five million patients in the U.S. could benefit from a beta-blocker added to their therapy."
Intercardia structured the deal with Astra Merck in a way that would let Intercardia increase its share of product sales by taking on some of the development risk, Love said. As part of its development costs Intercardia made a $10 million payment to Astra Merck in December 1997 and agreed to pay up to $11 million for one-third of product launch costs. The company estimated costs to complete development and prepare the new drug application at $15 million to $20 million. Astra Merck had spent $15 million on Bextra development as of April 30.
Outside the U.S. and Japan, Bextra is being developed with BASF AG, of Ludwigshafen, Germany. Intercardia was paid $3 million initially in that collaboration, and will get another $10 million upon regulatory approval in a major European Community member state, as well as 40 percent of profits.
Intercardia's position with Bextra was weakened somewhat when the beta-blocker carvedilol gained U.S. approval in May 1997 for treating congestive heart failure (CHF).
The drug is owned by Hoffmann-La Roche Inc., of Nutley, N.J., and licensed in the U.S. to London-based SmithKline Beecham plc. Earlier this year, Merck KgaA, of Darmstadt, Germany, halted early a European study of its 2,650-patient CHF trial of bisoprolol, with data showing improved survival in the drug group. Astra's beta-blocker Toprol already is approved in the U.S. for hypertension and angina.
Interneuron Pharmaceuticals Inc., of Lexington, Mass., owns about 62 percent of Intercardia's 7.3 million outstanding shares. Intercardia reported cash and equivalents of $22.4 million as of June 30.
Intercardia's stock (NASDAQ:ITRC) closed Thursday at $4, unchanged. *