Chiron Vaccines Submits Product License Application for Genetically Engineered DTaP Vaccine.

EMERYVILLE, Calif.--(BUSINESS WIRE)--Oct. 1, 1996--Chiron Corporation (NASDAQ: CHIR) announced today that its Chiron Vaccines business unit has submitted a product license application (PLA) to the United States Food and Drug Administration (FDA), seeking clearance for the marketing of Pertugen, a diphtheria, tetanus and genetically engineered acellular pertussis (DTaP) vaccine for infants and children.

One of a new generation of vaccines that would make childhood immunization safer, Pertugen is the first DTaP vaccine derived though the use of recombinant DNA technology to detoxify the pertussis toxin. In clinical trials, immunization of infants with Pertugen was highly protective against pertussis, also known as whooping cough. Further, Pertugen was associated with fewer of the potentially serious side effects of currently used whole-cell DTP vaccines.

"Chiron vaccines is committed to the development of safer, more effective vaccines, and is pleased that years of research are now resulting in the development of novel products," said Dino Dina, M.D., president of Chiron Vaccines. "Pertugen is evidence of the value of using recombinant technology to produce vaccines that are safe and highly immunogenic."

Infants younger than one year of age are at most risk for whooping cough, which affects approximately 50 million individuals worldwide each year. In the United States, pertussis cases have plummeted from 260,000 cases annually before widespread immunization to an estimated 2,200 cases in 1996. The disease is marked by coughing and choking that often end in a "whooping" sound as the patient inhales.

In a double-blind clinical trial, physicians in Italy immunized 15,601 infants with either a U.S.-licensed whole-cell DTP vaccine, a chemically detoxified DTaP vaccine, a diphtheria and tetanus vaccine alone, or Pertugen. Vaccination was given as 2, 4 and 6 months of age, and the health of the infants was then closely monitored.

In the Feb. 8, 1996 New England Journal of Medicine, Donato Greco, M.D., and colleagues reported that the two DTaP vaccines studied in this trial produced significantly fewer adverse effects (including local swelling or tenderness, irritability, fever and persistent crying for 3 or more hours) than the whole-cell vaccine.

The trial data also suggest that Pertugen may produce fewer cases of local swelling and fewer rectal temperatures greater than or equal to 38 degrees centigrade than the chemically detoxified DTaP vaccine included in the trial.

In the Italian Efficacy Trial, the surveillance period for the primary analysis of vaccine efficacy began at approximately 7 months of age, or 30 days after completing the three dose vaccination series, and continued for an average duration of 17 months (Stage I).

During Stage I, Pertugen was found to be highly effective against developing laboratory-confirmed whooping cough associated with 21 days or more of severe coughing (84 percent efficacy, compared to the rate of disease in infants receiving the control vaccine consisting of diphtheria and tetanus toxoid vaccine without pertussis).

Pertugen also proved more than twice as effective as the U.S.-licensed whole-cell vaccine, which was only 36 percent effective.

Data from the Italian Efficacy Trial also suggested that Pertugen provided better protection for infants before completing the immunization series. Prior to beginning Stage I, there were significantly fewer cases of whooping cough in the infants immunized with Pertugen than in the group immunized with the whole-vaccine (p less than 0.01). Also, there were fewer cases of pertussis in the group immunized with Pertugen than in the group immunized with the chemically detoxified acellular pertussis vaccine.

In addition to earlier protection, the advantages of the use of recombinant DNA technology were evident during extended blinded follow-up of infants receiving one of the two DTaP vaccines in the Italian Efficacy Trial. In May 1996, Greco and co-workers from Italy reported at the Annual Meetings of The American Society of Pediatrics and The Society of Pediatric Research held in Washington, D.C., that Pertugen's protection after the third immunization extended to an average age of 33 months, well beyond the age when most children in the United States would receive their fourth (or booster) immunization.

Further, during the extended follow-up in Stage II, the risk of developing whooping cough was 50 percent lower in children previously immunized with Pertugen than in children previously given the DTaP vaccine containing the chemically detoxified acellular pertussis vaccine (18 cases vs. 36 cases, p=0.015).

"The safety and efficacy improvements demonstrated by DTaP vaccines, and in particular Chiron's recombinant acellular pertussis vaccine, are a potential benefit to U.S. public health," concluded Dina. "For years, parents and physicians have been asking for a safer vaccine against pertussis. With the availability of DTaP vaccines such as Pertugen, there not only will be greater protection than with some traditional whole-cell pertussis vaccines, but compliance with the recommended immunization schedule for children should increase because of the superior tolerability associated with DTaP vaccines."

Chiron Vaccines, with operations in Emeryville, Calif.,; Siena, Italy; Marburg, Germany; and Amsterdam, The Netherlands, is researching and developing novel and improved vaccines for bacterial and infectious diseases, as well as new adjuvants to boost the immunization power of candidate and existing vaccines. The company has current research and clinical development programs for a broad range of pediatric and adult vaccines.

Other candidate vaccines in clinical or pre-clinical trials include an adolescent and adult pertussis vaccine, as well as vaccines to prevent genital herpes, cytomegalovirus (CMV), HIV, cancer, hepatitis C virus (HCV), meningococcus C, rabies and Helicobacter pylori infection.

Chiron Corporation, headquartered in Emeryville, Calif., near San Francisco, is a science-driven healthcare company that combines diagnostic, vaccine, and therapeutic strategies for controlling disease. Chiron participates in four global markets; diagnostics, including immunodiagnostics, critical care diagnostics, and new quantitative probe tests; ophthalmic surgical products for the correction of vision; pediatric and adult vaccines; and therapeutics, with an emphasis on oncology and infectious diseases. Chiron also has research programs underway in gene therapy and gene transfer, combinatorial transfer, combinatorial chemistry, cardiovascular disease and critical care.

This press release contains forward-looking statements relating to future events at Chiron. Actual events may differ materially from Chiron's expectations. Chiron refers the reader to documents that Chiron files with the Securities and Exchange Commission, including the section, "Factors That May Affect Future Operating Results" from the company's most-recent Form 10-Q report, for a further discussion of important factors that could cause actual performance to differ from Chiron's current expectations and the forward-looking statements contained in this press release.

CONTACT: Chiron Corp.

Larry Kurtz, 510/601-2476