An infection-fighting agent that is not an antibiotic has passedits Phase II clinical trials with high marks, according to resultsreported in San Diego over the weekend.
Speaking Saturday at the Second International Congress onBiological Response Modifiers, Gary R. Ostroff, vice-presidentof research at Alpha-Beta Technology Inc., told some400 clinicians that Betafectin, the company's anti-infectivecarbohydrate, had shielded 47 percent of post-surgery patientsfrom infection, while 100 percent of placebo controlscontracted minor or major infections. The session was titled"New Applications of Biological Response Modifiers inInfectious Disease, HIV and Cancer."
The conference is co-sponsored by eight leadingpharmaceutical companies, plus Amgen Inc. and ImmunexCorp.
Twenty-four adults of both sexes (of 30 eventually enrolled inthe Phase II study) undergoing major thoracoabdominalsurgery at two Boston-area hospitals received four doses ofBetafectin or placebo before and soon after their operations.Most of the procedures involved cutting into liver, pancreas,stomach or esophagus, which by their nature expose thepatient to high risk iatrogenic bacterial and yeast infections.
Ostroff told the asembled infectious-disease physicians andoncologists that the first interim results of the Phase II trial,which began last August, found that 45 percent of the nineplacebo subjects suffered minor infection, such as urinary-tractinfection, bronchitis or cellulitis. Another 22 percent, withfever above 38 degrees Celsius, were presumed infected; andpositive blood culture or local pathogen, with chills and/orfever, confirmed severer infection in 33 percent. Among the 15who received Betafectin prophylaxis, the percentages were 40percent minor, 13 percent presumed and none severer.
Alpha-Beta (NASDAQ:ABTI) of Worcester, Mass., will report thisdata to the FDA "as soon as our analysis is finalized," whileproceeding with a second arm of the Betafectin Phase II study,Spyros Jamas, its president and chief executive officer, toldBioWorld. This study involves twice as manysurgery patients -- 60 instead of 30 -- treated at four hospitals,two each in Boston and Worcester. They will receive graduateddoses of the drug (or placebo) rather than the fixed 0.5 mg./kg.of the just-completed study. This dosage was repeated fourtimes, 24 and 12 hours before surgery, and 48 and 96 hoursafter.
Betafectin is a complex configuration of a simple sugarmolecule. It consists entirely of glucose, engineered in a three-dimensional triple helix. This structure finds receptors on onlytwo kinds of white blood cells (WBCs), neutrophils andmonocytes, which patrol the body's bloodstream looking forpathogens to engulf and destroy.
Betafectin, at the Phase II dosage, Jamas explained, "stimulatesthis phagocytic and killing activity." At larger doses, it has beenshown in animals to step up the bone marrow's output of theseWBCs, as well as their activity. This second effect is double-edged, he cautioned, because clinicians rely on elevated WBCcounts as a diagnostic early-warning sign of infection.
To verify that Betafectin actually killed trial patients'pathogens, WBCs skimmed from their blood samples wereincubated in vitro with Candida albicans, a common cause ofpost-operative yeast infections. One white blood cell inparticular, polymorphonuclear leukocytes, can kill Candidapathogens. But after major surgery, patients are oftenimmunosupressed by the rigors of the intervention, and cannotgenerate enough of these cells to overwhelm the yeasts.
The Phase II trial results reported here showed that in the first24 hours after surgery, 30 percent of the placebo subjects weretoo immunosuppressed to perform the microbial killing, ascompared with only 5 percent of the Betafectin recipients.
Alpha-Beta intends to reserve worldwide manufacture ofBetafectin, for which other medical indications are in or nearclinical trials. Ground-breaking for its future manufacturingfacility in Rhode Island is expected "within the first quarter ofthis year," said Jamas. The company also will exercise exclusivemarketing rights to the drug in North America, and is now"evaluating the pros and cons" of partnering sales in Europeand Japan.
Alpha-Beta's stock closed unchanged on Friday at $21 a share.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.