By Randall Osborne
As the influenza season gets under way, Gilead Sciences Inc. is moving briskly ahead with Phase II/III trials of GS 4104, its drug designed to treat the virus and relieve symptoms.
Gilead, of Foster City, Calif., completed Phase I and Phase II studies earlier this year. The Phase II/III trials will be held at up to 75 sites in 29 states. Each state's study centers will be activated upon a regional flu outbreak, said Gilead spokesperson Susan Hubbard.
"We moved at lightning speed to get it up and running in time for this year's flu season," which runs through March in the Northern Hemisphere, Hubbard said. Up to 750 patients will be enrolled in the U.S. treatment studies, and up to another 750 will be enrolled in treatment studies in Canada, Europe and Hong Kong.
"We could have two centers that enroll 750 patients, or we could activate all 75," Hubbard said.
In the Phase II studies, patients were inoculated with the flu virus and then treated with GS 4104. Phase II/III trials will be conducted against natural infection.
"They should call within 36 hours of the symptoms' onset," Hubbard said. Patients will be directed to clinics near them, where they will be screened. The study will only accept nonvaccinated people afflicted with true signs of influenza, including fever of at least 100 degrees Fahrenheit and respiratory symptoms.
In separate prophylaxis studies, Gilead plans to enroll up to 1,500 patients. "We've already prescreened those patients and they will begin dosing once the flu comes to their area," Hubbard said.
Influenza season peaks in December, she added. If not enough patients are enrolled in the Northern Hemisphere for adequate studies, "we'll move on to catch the flu season in the Southern Hemisphere," Hubbard said.
When the Phase II/III studies are completed, Gilead will file a new drug application with the FDA, Hubbard said.
GS 4104 is an orally administered compound that inhibits the enzyme neuraminidase, which is required for all influenza strains, including A and B, to thrive. When the enzyme is inhibited, the virus cannot escape from infected cells and move to others. The drug is given in capsule form, once or twice per day.
Currently marketed treatments may work only against type A influenza strains, and may have adverse side effects with rapid development of resistance. Injected flu vaccines are formulated on advice from the U.S. Centers for Disease Control, in Atlanta, which provides an educated guess regarding which strains will be most prevalent.
The vaccines may not be efficacious for patients lacking a stable, healthy immune system, such as the elderly and children, Hubbard said — and, in any case, statistics show only about 15 percent of the population is being vaccinated.
GS 4104 also is easier to administer than other proposed treatments, Hubbard said. Aviron Inc., of Mountain View, Calif., is developing an influenza vaccine delivered by way of nasal spray. The vaccine was shown effective in Phase III clinical trials in healthy young children. (See BioWorld Today, July 15, 1997, p. 1.)
"Try to imagine getting your child to take an inhalant, or an elderly person who is coughing and wheezing," she said.
Influenza infects about 120 million people each year in the U.S., Europe and Japan. Mortality is highest among high-risk patients such as the elderly and people with heart and lung disorders.
Gilead is developing GS 4104 in collaboration with Hoffman-La Roche Ltd., of Basel, Switzerland, in a deal worth up to $50 million. Starting the Phase II/III trial program — in which the first patient was enrolled earlier this week — triggered a $3 million milestone payment to Gilead. (See BioWorld Today, Oct. 1, 1996, p. 1.)
Gilead's stock (NASDAQ:GILD) closed Tuesday at $37, up $3.188. *