By Mary Welch
Shaman Pharmaceuticals Inc. reported positive, statistically significant results from two separate Phase II dose optimization studies of Provir against acute watery diarrhea.
Coupled with the Phase III trial results of Provir in HIV-patients, the trials "show that Provir works regardless of the patient population, whether chronic or acute, and regardless of the immune state," said Lisa Conte, president and CEO of South San Francisco-based Shaman.
"These results are strong, significant and powerful," Conte said.
Provir is derived from an extract of the croton plant, found in Latin America. Rather than attacking infectious microbes or inhibiting gastrointestinal activity, the drug targets the underlying cellular mechanism for the diarrhea by blocking chloride secretion. In most cases, a patient's own immune system can eliminate the microbes. (See BioWorld Today, Oct. 31, 1997, p. 1.)
Both studies for acute watery diarrhea were double-blind, randomized and placebo-controlled. The first study, for traveler's diarrhea, involved 184 Americans traveling to Jamaica and Mexico, who were treated for two days on an outpatient basis with either a placebo or with one of three Provir doses given four times per day: 125mg, 250 mg, or 500 mg.
Traveler's Study Aced Endpoint At All Doses
In the key efficacy endpoint -- time to last unformed stool over 48 hours -- all doses reached a highly statistically significant result vs. the placebo.
The second study tested Provir in Venezuelan nationals who locally contracted acute watery diarrhea. One hundred and forty patents were treated in a hospital and given 125 mg four times a day for two days. Again, Provir showed a statistically significant earlier end to the problem than when a placebo was used.
However, in the 250 mg and 500 mg doses, the drug did not achieve statistical significance. The study affirmed that Provir is well tolerated.
"'Acute watery diarrhea' is the umbrella term," said Conte. "In traveler's diarrhea, Americans are exposed to new bugs and their cases are more severe, lasting four to seven days. In the case of the Venezuelans, they developed acute watery diarrhea with bugs that they've encountered before -- really all their life -- and should have built up some antibodies to these bugs. It's a different immunological basis."
Shaman will start Phase III trials in traveler's diarrhea in the near future and hopes to get a labeling indication for acute watery diarrhea based on those results.
The company's Phase III trial for Provir in AIDS-related diarrhea is now 75 percent enrolled and ahead of schedule. A new drug application filing is expected in the first quarter of 1999, with the drug possibly hitting the market as early as July 1999, if approved.
This month, Shaman filed to raise $16 million through royalty-based stocks to fund the marketing of Provir in the U.S., and the company is talking with other firms to market Provir for all three indications, pending approvals, outside the country.
Shaman's stock (NASDAQ:SHMN) closed Thursday at $3.093, down $0.218. *