By Frances Bishopp
Aviron Inc. and the National Institute of Allergy and Infectious Diseases (NIAID) reported Phase III clinical trial results of an influenza vaccine administered in a nasal spray demonstrate the product was effective at preventing flu in healthy, young children.
The attenuated (weakened) live-virus vaccine provided 93 percent protection against influenza. Only one percent of 1,070 children who received the vaccine developed culture-confirmed influenza during last year's flu season vs. 18 percent of 532 children of the same age who received placebo.
The news shot Aviron's stock (NASDAQ:AVIR) up 28 percent, closing Monday at $17.125, a $3.75 increase.
The Phase III, double-blind trial was conducted at 10 sites nationwide, including six vaccine and treatment evaluation units supported by NIAID, of the National Institutes of Health, in Bethesda, Md., and four sites supported by Aviron, of Mountain View, Calif.
The study enrolled 1,602 children from 15 months to 6 years of age. Approximately two-thirds received Aviron's intranasal, cold-adapted influenza vaccine and one-third received a placebo.
Following their vaccinations, the children were monitored for flu symptoms during the 1996-1997 influenza season. The vaccine protected children from influenza caused by both the A and B strains of the virus circulating last year.
In the study, each child was assigned at random to receive either the intranasal vaccine or placebo. The 1,314 children enrolled in the study between mid-August and mid-October 1996 received two doses, spaced about two months apart.
The 288 children who entered the study later received a single dose. A dose comprised two tiny squirts (0.25 milliliter per nostril) of spray containing the vaccine or a placebo. Both one or two doses were efficacious against strains circulating last year.
The results represent Aviron's first Phase III results, Leighton Read, chairman and CEO of Aviron, told BioWorld Today, and "are very significant in the life of the company. This milestone is the basis of a very successful collaboration between ourselves and NIH. It is a very nice example of government and industry working together."
The company plans to file a product license application (PLA) with the FDA before mid-year 1998, Read said. The PLA will include the use of the vaccine for children and healthy adults.
Currently, Read said, a consistency lot trial is under way (to determine consistency of one lot of the vaccine to the next lot) as well as a second Phase III trial in the same 1,602 children to look at the use of the vaccine in subsequent influenza years.
Also, Read said, several Phase III trials are planned for this coming flu season: a safety study in asthma patients and another safety study that will combine the vaccine with the flu shot.
The cold-adapted influenza vaccine is trivalent, containing two different influenza A strains and one influenza B strain. The internal flu proteins from these master strains of influenza A and B virus grow at cooler temperatures and combine with hemagglutinin and neuraminidase, the surface proteins found on contemporary circulatory viruses. The vaccine is a modified living influenza virus altered to make it non-virulent.
In addition to being delivered in a nasal spray rather than injected into the bloodstream, Aviron's product differs from currently approved vaccines by activating antibodies against the virus in the mucosal immune systems as well as the systemic immune system. The vaccine also stimulates a strong cytotoxic T cell response.
Aviron's flu vaccine, like other live-virus vaccines, produces an infection without causing illness, Read said.
Wyeth-Ayerst Laboratories, of King of Prussia, Pa., studied the vaccine from 1989 to 1993 before dropping development. Wyeth-Ayerst is a subsidiary of American Home Products Corp., of Madison, N.J.
In 1995, Aviron licensed the vaccine from the University of Michigan, Ann Arbor, and entered into a cooperative research and development agreement with NIAID for its development into a commercial product.
In July 1996, Aviron postponed its initial public offering (IPO) of 3 million shares due to a down market. In November 1996, the company completed a scaled-down version of the IPO, selling 2 million shares at $8 per share for $16 million.
In April 1997, Aviron raised $15 million in a private placement to Swiss investors. Biotech Target S.A., of Zurich, purchased 1.7 million shares of Aviron for $8.75 per share. Biotech Target is part of Biotech Growth S.A., of Zurich, another fund with an equity stake in Aviron. Together the funds own 18 percent of Aviron.
The company has a collaboration with South Korean drug maker Sang-A, a subsidiary of the Hanbo Group, in Seoul, to manufacture the product and sell it in Korea. Aviron also has a collaboration with London-based SmithKline Beecham plc for vaccines against Epstein-Barr virus, which causes infectious mononucleosis.
Other vaccines under development by Aviron target cytomegalovirus, herpes simplex virus and respiratory syncytial virus.
Aviron's cash on hand, as of March 31, 1997, totaled $27.7 million. *