By Randall Osborne
Despite positive results from what was intended as a pivotal Phase III trial with Provir for AIDS-related diarrhea, Shaman Pharmaceuticals Inc. came away less than encouraged from a meeting with the FDA regarding the company's plan to file a new drug application (NDA).
Lisa Conte, president and CEO of South San Francisco-based Shaman, said the company was "surprised" by the FDA's new approach.
"It was not a question of therapeutic benefit of the product in the sickest patients, or safety," Conte told BioWorld Today. "It was a change of tone to a very conventional view of what's required for a successful NDA."
Shaman is reviewing its filing strategy, which could include a labeling change and more trials. The firm's stock (NASDAQ: SHMN) dropped 44 percent Wednesday, closing at $1.031, down $0.812, after trading as low as 75 cents during the day.
"We have no conclusions, no outcomes, nothing to report" regarding next steps, Conte said. "We're juggling several things, and we have some potential corporate partners we have to bring into the loop."
An oral compound, 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 diarrhea by blocking chloride secretion. Last December, Shaman disclosed positive data from a 400-patient trial of Provir, which had been designated a fast-track product by the FDA. (See BioWorld Today, Dec. 23, 1998, p. 1.)
Earlier interactions with the FDA had been "smaller and more informal," Conte said. "This one was two to three times the size of previous meetings."
FDA officials told the company of requirements "different from what we've been led to believe before," she added. "It was not a forum in which there could be any negotiations, discussions or trade-offs." Some discussion pertained to statistical significance and sample size for studies on drugs for chronically ill populations, she said.
Conte said the company will disclose further plans within the next several weeks.
Earlier this month, Shaman enrolled its first patients in an open-label study of Provir, designed to provide access to the drug for patients from previous trials. The company also is developing an oral anti-fungal drug, as well as oral drugs for Type II diabetes. n