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EMERYVILLE, Calif.--(BUSINESS WIRE)--July 13, 1995--Chiron Corporation (NASDAQ:CHIR) announced today that a large-scale government-sponsored clinical trial conducted in Italy comparing two acellular pertussis vaccines to a whole-cell pertussis vaccine currently licensed in the United States has demonstrated that these acellular pertussis vaccines are much more effective and safer than whole-cell pertussis vaccine.

The two acellular pertussis vaccines tested in Italy showed equal overall protection, but the Chiron Biocine genetically engineered acellular pertussis vaccine was found to have several distinguishing characteristics versus the chemically detoxified acellular vaccine from SmithKline Beecham with which it was compared, including a better safety profile. The Chiron Biocine vaccine is the only acellular pertussis that uses genetic engineering to eliminate the toxic activity of the pertussis antigen while still retaining the antigen's ability to generate a protective immune response. The results of the Italian trial confirm the benefits of this approach: the Chiron Biocine vaccine was highly effective, measurably safer, and protected infants from disease sooner than the SmithKline Beecham vaccine. These findings, all of which are statistically significant, came in a Phase 3 clinical trial supported by the National Institute of Allergy and Infectious Diseases (NIAID). Results of the trial were presented today in Stockholm by clinical investigators from the Istituto Superiore di Sanita of Italy.

In the Italian trial, 15,601 infants were enrolled between September 1992 and September 1993 at 62 local health units in four regions. A total of 14,832 infants received all three immunizations at two, four and six months with one of four vaccines: a genetically engineered DTaP (acellular pertussis combined with diphtheria and tetanus toxoids) vaccine formulation from Chiron Biocine; a chemically detoxified DTaP vaccine formulation from SmithKline Beecham; a DTP (whole-cell pertussis combined with diphtheria and pertussis) vaccine formulation from Connaught Laboratories Incorporated; or a placebo of DT (diphtheria and tetanus toxoids) from Chiron Biocine. The average duration of follow-up beginning 30 days after the third dose was 17.2 months. A total of 4,480 infants received the full regimen of three doses of the Chiron Biocine DTaP vaccine.

In the Italian trial, the Chiron Biocine genetically engineered acellular pertussis vaccine had 84 percent efficacy -- that is, the risk of confirmed pertussis (defined as 21 days or more of paroxysmal coughing, a definition developed by the World Health Organization -- WHO) was reduced by 84 percent among vaccinated infants compared to infants vaccinated with placebo. The SmithKline Beecham acellular pertussis vaccine was equally effective. Both acellular pertussis vaccines were substantially more effective than the currently licensed whole-cell pertussis vaccine, which reduced the risk of pertussis disease by 36 percent. Also, there were significantly fewer cases of pertussis with onset between the first dose and 30 days following the third dose among infants receiving the Chiron Biocine genetically engineered acellular pertussis vaccine compared with those receiving the chemically detoxified acellular pertussis vaccine and the whole-cell pertussis vaccine.

In general, fever and local side effects such as redness, swelling and tenderness at the injection site in the infants receiving both DTaP vaccines were much less frequent than seen in the infants who received the whole-cell pertussis vaccine. In addition, according to the results from the Italian study, the genetically engineered DTaP vaccine from Chiron Biocine was associated with significantly lower incidence of fever following each injection, and significantly fewer infants who exhibited combinations of side effects -- such as fever plus redness or swelling -- compared with the infants who received the chemically detoxified acellular pertussis vaccine.

Both the Chiron Biocine genetically engineered acellular pertussis vaccine and the chemically detoxified acellular pertussis vaccine in the Italian trial contain three Bordetella pertussis antigens: an inactivated form of pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN -- an outer membrane protein), combined with diphtheria and tetanus toxoids. However, the Chiron Biocine acellular pertussis vaccine is the only vaccine that uses genetic engineering instead of chemical processes to inactivate the pertussis toxin.

The Chiron Biocine approach is designed to eliminate the toxic activity of the pertussis toxin while preserving the immunological properties of this antigen that play a major role in conferring protection against disease. As a result, the dose of PT required for the Chiron Biocine vaccine is five-fold lower than the dose of PT in the chemically detoxified acellular pertussis vaccine, yet provides superior immunogenicity while eliciting fewer side effects.

In addition to its superior immunogenicity, the presence of a non-toxic, naturally produced form of pertussis toxin is important in improving the overall safety of the vaccine. Genetic detoxification ensures that no active form of the pertussis toxin is present, while chemically detoxified pertussis toxins may revert to toxicity.

"We congratulate the multinational efforts made by the NIAID, the Istituto Superiore di Sanita, the manufacturers and the parents and children who participated as subjects, for a landmark study that establishes in a definitive way the value of acellular pertussis vaccines," said Dino Dina, M.D., president of Chiron Biocine. "The excellent safety and efficacy data for acellular pertussis vaccines from the Italian trial demonstrate that they will play a major role in further controlling the spread of this serious infection, and should rapidly replace the current generation of whole cell pertussis vaccines. We have confirmed that we will be able to make regulatory filings based on the data we now have in hand. We look forward to working together with regulatory authorities to make our vaccine available as soon as possible."

"We are especially pleased at the high level of efficacy achieved by our acellular pertussis vaccine, and by the excellent safety profile of the Chiron Biocine genetically engineered acellular pertussis vaccine," added Dina. "The comparative safety data confirm the benefit of the rational approach to vaccine development possible through the application of molecular biology. Because we engineer genetic substitutions in the pertussis toxin, there is no risk of reversion to toxicity and we can have greater consistency in the method of production. We also can use a lower dose to achieve increased immunogenicity with fewer side effects. Chiron Biocine has been the pioneer company in the development and introduction of the only currently available genetically engineered vaccines, the hepatitis B vaccine and acellular pertussis vaccine. Using genetic engineering for modern vaccine development is a cornerstone of Chiron Biocine's programs for a broad range of infectious diseases such as genital herpes, HIV, cytomegalovirus and hepatitis C virus."

The Chiron Biocine acellular pertussis vaccine studied in the Italian clinical trials being reported was developed at Chiron's business unit Biocine S.p.A. by a team led by Dr. Rino Rappuoli. A formulation of this vaccine, without the diphtheria and tetanus toxoids, has been on the market in Italy since late 1993, sold under the trade name Acelluvax(TM). The PT antigen used in Acelluvax, together with diphtheria and tetanus toxoids, forms the DTaP combination that was used in the Italian trials. This vaccine is in the final stages of licensing in Italy.

"We are looking forward to building on the success that Acelluvax has had in Italy as we begin sales across Europe and in the United States," said Mario Lorenzoni, managing director of Biocine S.p.A. "Already, more than 1.5 million doses of Acelluvax have been sold for use in Italy. We also are looking forward to pursuing other innovative vaccine products resulting from collaborations between Siena and Emeryville, such as our new adjuvanted influenza vaccine."

The Chiron Biocine DTaP combination also is being studied in an ongoing large field trial in Sweden, also under the sponsorship of NIAID, that compares the acellular pertussis vaccines of three manufacturers with a whole-cell pertussis vaccine among 82,000 infants. In 1994, Chiron Biocine completed and reported on a U.S. clinical trial of its DTaP vaccine at Kaiser Permanente Hospital in Northern California, which showed that the vaccine was very well tolerated in 2,000 infants, and substantially safer than the licensed whole-cell pertussis vaccine from Connaught given to 500 infants. In 1992, a Phase 2 comparative trial carried out by NIAID in the United States showed that Chiron Biocine genetically detoxified PT antigen had superior immunogenicity in children when compared with 11 other chemically detoxified PT antigens.

Pertussis, also known as whooping cough, is a highly contagious bacterial infection of the respiratory tract caused by the bacterium Bordetella pertussis. Pertussis causes violent spells of coughing that make it hard for a patient to eat, drink or even breathe.

The World Health Organization estimates that more than 50 million cases of pertussis occur worldwide annually. The disease is responsible for approximately 350,000 deaths in unvaccinated persons per year. In the United States, 6,586 cases of pertussis and 11 pertussis-related deaths were reported to the Centers for Disease Control and Prevention (CDC) in 1993. Provisional CDC data for 1994 show 4,698 pertussis cases and eight deaths. Due to the difficulties in diagnosing pertussis and confirming the disease using laboratory tests, the CDC estimates that reported cases represent approximately 10 percent of actual pertussis cases in this country.

Chiron Corporation, headquartered in Emeryville, California, applies biotechnology and other techniques of modern biology and chemistry to develop products intended to improve the quality of life by diagnosing, preventing and treating human disease. Chiron participates in four markets: 1) diagnostics, including immunodiagnostics, critical care diagnostics and quantitative bDNA probe tests; 2) therapeutics for cancer and infectious disease; 3) adult and pediatric vaccines, and 4) ophthalmic instruments and devices used for the surgical correction of vision. Additional research programs are underway in gene therapy and gene transfer, combinatorial chemistry, cardiovascular disease and critical care. -0-

Note to Editors: Additional releases and backgrounders are available from NIAID Office of Communications, 301/402-1663.

CONTACT: Chiron Corporation, Emeryville

Larry Kurtz, 510/601-2476
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Date:Jul 13, 1995
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