Cytel Corp.'s lead cell adhesion blocker failed to beat placebo in aPhase II trial assessing the carbohydrate-based small molecule'sability to reduce cardiac reperfusion injury in those with heart attackstreated with angioplasty.
The San Diego company reported late Wednesday that it stopped thestudy after an interim analysis showed the drug, Cylexin, produced nobenefit. Company officials said the data, together with positive datafrom a separate trial of Cylexin in an orphan indication, would haveto be fully analyzed before decisions are made about the future ofCylexin.
The Phase II study was designed to enroll 156 patients. It wasstopped after 74 patients were treated. Scans taken at the time ofangioplasty and 120 to 168 hours later were used to measure howmuch heart muscle remained vs. how much was at risk.
Reijer Lenstra, an analyst at Smith Barney in New York, said Cytel'sapproach was an interesting one for prevention of reperfusiondamage. "They used the right model, angioplasty for heart attacks,"he said. "It's disappointing it didn't work," he said, adding, "It mayhave implications for others looking at reperfusion injuries."
Cytel's stock (NASDAQ:CYTL) fell 34 percent Thursday, or $2.88,to close at $5.63 in trading of 2.3 million shares.
Last year Cytel signed a potential $70 million deal with SchwarzPharma AG, of Monheim, Germany, to develop and marketcarbohydrate selectin blockers, including Cylexin. SumitomoPharmaceuticals Co. Ltd., of Osaka, Japan, has Cylexin rights in theFar East. (See BioWorld Today, May 19, 1995, p. 1.)
Schwarz paid Cytel $4 million upon signing the deal, half in equity ata premium, and made a $2 million milestone payment late last year.The German company also has funded 75 percent of developmentsince the partnership was established.
"They haven't digested the news yet," Karin Eastham, Cytel's vicepresident and chief financial officer, said of the corporate partners."We can't say anything definitively until all the data have beenanalyzed."
Lenstra said, however, "This might be the end of Cylexin as a drug.Perhaps I'm too pessimistic. But if it doesn't work in a great model,angioplasty for heart attack, where now is it going to work?"
Eastham pointed out there is a lot going on at Cytel beyond Cylexin,including the technology used to manufacture the drug. She said thecarbohydrate synthesis technology can be applied to other complexcarbohydrates as evidenced by the option Abbott Laboratories, ofAbbott Park, Ill., acquired to use it in the manufacture ofcarbohydrates that can be added to nutritional products.
Another program at Cytel is peptide-based therapeutic vaccines. Thelead product there is Theradigm-HBV, which is in an open-labelstudy for hepatitis B that is producing encouraging data, Easthamsaid. Cytel hopes to take the candidate into Phase III studies nextyear, she said.
Theradigm is designed to produce a specific cytotoxic T lymphocyteimmune response. With the results to date in HBV, company officialsplan to move forward with candidates for hepatitis C and HIV, aswell as a proof-of-concept study in cancer, Eastham said.
Lenstra said he liked Cytel's Theradigm technology more than itswork in cell-adhesion blockers. He said he "was not blown away" bythe positive data of Cylexin released recently in the lung reperfusioninjury, but that indication didn't represent a viable marketopportunity anyway.
Cylexin binds to both E- and P-selectin receptors, each of which isbelieved to be involved in neutrophil migration. The drug wasdesigned to prevent reperfusion injury upon return of blood flow totissue that has been ischemic. Injury occurs when excessiveneutrophils migrate from the blood stream to surrounding tissue andrelease toxins that damage healthy tissue in the process.
Cytel had $35.9 million in cash and 24.8 million shares outstandingon March 31, 1996. The company projected a burn rate of $17million for the year. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.