Acambis plc filed a biologics license application seeking approval of Arilvax as a vaccine to prevent yellow fever.
The company, based in Cambridge, UK, with offices in Cambridge, Mass., believes the FDA will act on its application in 12 to 15 months, said Lyndsay Wright, Acambis' director of communications.
Arilvax is a live, attenuated vaccine marketed in 10 countries including the UK for yellow fever, a vector-borne hemorrhagic disease endemic or epidemic in tropical South America and Africa. Wright said U.S. sales would target the travelers' market.
In a prepared statement, John Brown, Acambis' CEO, said, "This submission marks a major achievement for Acambis, not only because this is our first-ever BLA, but also because it is the first time a BLA has been submitted electronically to the CBER [Center for Biologics Evaluation and Research] vaccine division of the FDA. It is another significant milestone in our plan to establish a travel vaccines franchise in North America."
Acambis, which also is working on a smallpox vaccine for the U.S. government, gained U.S. rights to Arilvax in 1999 by acquiring OraVax Inc., of Cambridge, Mass. Before Acambis came into the picture, OraVax had purchased the rights from a company called Medeva plc, of Speke, UK, which eventually sold its vaccine capabilities to PowderJect Pharmaceuticals plc, of Oxford, UK.
In May, Emeryville, Calif.-based Chiron Corp. spent $880 million to acquire PowderJect, thereby inheriting the Acambis deal.
So, as it stands today, Acambis has the right to sell Arilvax in the U.S. if it can win regulatory approval. Chiron, via Chiron Vaccines, has the right to buy back 50 percent of the profits in return for refunding Acambis the cost of its trials, which is in excess of $13 million, Wright said.
Acambis will market Arilvax in the U.S. via its subsidiary, Berna Products Corp., of Coral Gables, Fla.
Clinical trials supporting the BLA recently were released as abstracts at the American Society of Tropical Medicine and Hygiene meeting in Philadelphia.
Among the trials was a Phase III study that evaluated more than 1,000 children ages 9 months to 10 years who lived in Sullana, northern Peru. That was a randomized, double-blind study designed to determine the safety, tolerability and efficacy (by measurement of neutralizing antibody responses) of two yellow fever vaccines: Arilvax and YF-VAX (made by Aventis-Pasteur, of Swiftwater, Pa.). The primary outcome measure was a comparison of seroconversion rates in patients seronegative to YF-VAX at baseline, and the primary statistical endpoint was a test of non-inferiority of Arilvax compared to YF-VAX.
Of the 1,107 children who enrolled, 1,072 were followed up. A total of 738 received Arilvax (708 nonimmune) vs. 369 who received YF-VAX (358 nonimmune). Seroconversion rates among nonimmune children were higher (86.5 percent) among Arilvax, compared to YF-VAX recipients (79 percent, p=0.0031). Post-vaccination geometric mean neutralizing antibody titer responses also were found to be similar for both products. Most adverse events were mild and resolved without treatment.
The company said the pediatric study provides pivotal data that demonstrated the immunogenicity of Arilvax vaccine compared to the only FDA-approved yellow fever vaccine.
Another trial commissioned for the FDA application was a randomized, double-blind, multicenter comparison of immunogenicity, safety and tolerability of Arilvax and YF-VAX. The safety population included 715 Arilvax subjects and 725 YF-VAX subjects. Adverse event profiles were distinct in that fewer (p<0.001) people reported local injection-site pain (23.9 percent vs. 39.4 percent), edema (8.5 percent vs. 19.9 percent) and inflammation (15.8 percent vs. 29.5 percent) after Arilvax. Serum samples were provided by 283 Arilvax and 291 YF-VAX participants demonstrating 98.6 percent and 99.3 percent seroconversion rates after one month.
And the company looked at safety in a 3,092-person open-label, multicenter study. Commonly reported adverse events were asthenia (47.3 percent), headache (46.2 percent), malaise (37.9 percent) and myalgia (33.8 percent).
Once vaccinated with Arilvax, theoretically a patient would have lifetime immunity from yellow fever, Wright said. However, the company expects the label to say the immunity lasts 10 years.