Washington Editor

Shares of Novavax Inc. surged 31 percent on preclinical data showing that its influenza vaccine technology has proved effective against a feared strain of bird flu.

Scientists at the specialty biopharmaceutical company worked with government collaborators on the research, which demonstrated that a vaccine against the H9N2 avian flu strain, produced with Novavax's Virus-Like Particle (VLP) technology, effectively protected animals when challenged with live virus. Detailed results were published in the Aug. 15, 2005, online edition of Vaccine.

"This is a better way to present an antigen to the immune system," the company's president and CEO, Rahul Singhvi, told BioWorld Today.

The H9N2 product involves VLP vaccines constructed from the proteins HA, NA and M1, which were produced from genes cloned from avian H9N2 influenza virus. It uses recombinant protein technology to imitate the 3-dimensional structures of the virus to provide protection without the risk of infection or disease.

The animals, vaccinated with a low dose of VLP without the addition of an adjuvant, developed antibodies after the first subcutaneous immunization. Immune responses increased after booster inoculation, and were shown to be protective when challenged with the H9N2 influenza virus.

"Part of the signals that are important for generating innate immunity, these so-called pathogen-associated molecular complexes, is the repeating nature that is present on viruses or particles that you wouldn't get on a purified subunit vaccine," explained Gale Smith, the company's vice president of vaccine development, adding that adjuvants are unnecessary because the particles themselves produce innate immunity. "That repeated nature is important overall in inducing innate immunity."

The H9N2 strain is one of two worrisome bird flu viruses gaining worldwide focus for their pandemic potential, and a number of large companies also are involved in research in the area. The antiviral drug Tamiflu (oseltamivir), a product of F. Hoffmann-La Roche Ltd., of Basel, Switzerland, has been shown to be effective against the H5N1 avian flu strain and a small quantity has been ordered for a national stockpile. Also, two other companies have received government contracts to produce a small quantity of H5N1 vaccines: Sanofi Pasteur, of Lyon, France, and Chiron Corp., of Emeryville, Calif. The latter also has a government contract to test a vaccine against H9N2. On its own, the National Institutes of Health is testing vaccines in clinical trials against both strains.

In addition to Novavax's positive efficacy data, the Malvern, Pa.-based company said its three-day production process within an insect cell system can generate large quantities more quickly than existing egg-dependent manufacturing and newer cell-based methods.

"To have a process that is inherently cost effective because of high yield, the way we manufacture or the raw materials we use, is a huge competitive advantage for us," Singhvi said. "It's also the right thing to do from a public health standpoint."

He added that the VLP technology allows for production closer to the flu season for a standard flu vaccine - the company can engineer a VLP vaccine within a few weeks of the discovery of a new virus, after the publication of its DNA sequence data - and also allows for readiness in the face of a pandemic strain such as H9N2. Smith noted another advantage: Novavax's genetically engineered particles provide an exact match to a given flu strain, avoiding replication pitfalls inherent in current egg- and cell-based processes.

As a result, the VLP vaccines safely imitate whole-virus vaccines and cannot cause infection since they do not contain nucleic acid from a virus.

With the ability to induce innate immunity, ease of manufacturing, and being non-infectious, Smith told BioWorld Today, "I think you have the basis for a new generation of vaccines."

Novavax plans to soon advance its VLP technology into clinical trials of vaccines for both pandemic and seasonal versions of flu.

"We have committed to upgrading our facilities to GMP levels to create necessary clinical supplies," Singhvi said. "We will aggressively move to get this into the clinic."

The company, which already has tested VLP vaccines against the coming flu season's recommended strains, also plans to evaluate the technology in the H5N1 avian flu strain. The H9N2 vaccine study was partially supported by a grant from the National Institute of Allergy and Infectious Disease, part of the NIH in Bethesda, Md., and completed in collaboration with the Center for Disease Control and Prevention in Atlanta.

Apart from its flu research, the company also continues to progress VLP vaccines for AIDS and severe acute respiratory syndrome, also with the support of government grants.

"In SARS, we're in the first year of our development efforts," Smith said. "In HIV, we're further along, finishing the second year of a five-year program. It's very likely that this program will go forward into human studies, based on the data we've seen so far in small animals and primates."

In addition to Novavax's VLP technology, it also is developing another platform, micellar nanoparticles (MNP) technology, to create nanoparticles for transdermal formulation. Already, an estradiol emulsion product called Estrasorb has received FDA approval for the management of vasomotor symptoms in post-menopausal women. Other similarly formulated compounds also are in development, including Androsorb, a topical testosterone emulsion that has completed two Phase I trials.

On Thursday, the company's shares (NASDAQ:NVAX) gained 27 cents to close at $1.22, down from their peak of $1.43. Trading volume was especially heavy, with about 10.3 million shares changing hands, compared to a daily average of about 207,000 shares.

No Comments