SmithKline Beecham's New Acellular Pertussis Vaccine Demonstrates Enhanced Efficacy in Major NIAID Studies

STOCKHOLM, SWEDEN, July 13, 1995 - SmithKline Beecham (SB) announced today that the efficacy of its new acellular pertussis (whooping cough) containing vaccine, Infanrix, was confirmed in a landmark, placebo-controlled clinical trial, conducted by the United States National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID). This study was part of a co-ordinated effort to compare, for the first time, the efficacy of four acellular pertussis vaccines and a whole-cell vaccine. In two countries - Sweden and Italy - a total of 25,000 children were involved.

Until recently, vaccination has typically been with classical combined diphtheria (D), tetanus (T) and whole-cell pertussis (Pw) vaccines, commonly associated with a number of side effects. New acellular pertussis (DTPa) vaccines have been shown to cause significantly fewer side effects than whole-cell vaccines but until now have not been demonstrated to be effective for primary vaccinations in such a large group.

The three-year NIAID study in Italy included 15,601 children who were vaccinated with one of four vaccines: Infanrix, SB's new DTPa vaccine, another new acellular pertussis vaccine; a whole-cell pertussis vaccine (DTPw) or a diphtheria and tetanus vaccine without the pertussis component.

The two acellular vaccines were significantly more effective than the whole-cell vaccine. The SB DTPa and the other acellular vaccine had 84 per cent efficacy and the whole-cell vaccine demonstrated a 36 per cent level of efficacy. In addition, as expected, the acellular vaccines had dramatically fewer side effects than the whole-cell vaccine. The acellular pertussis vaccines both contained three components: pertussis toxoid (PT); filamentous haemagglutinin (FHA) and pertactin (69kDa outer membrane protein).

In the three-year NIAID study in Sweden, 9,829 children were vaccinated with one of four vaccines: an SB two-component acellular vaccine (containing only pertussis toxoid and filamentous haemagglutinin), a five-component acellular vaccine, the whole-cell pertussis vaccine (DTPw) or a diphtheria and tetanus vaccine. The five-component acellular vaccine in the study was more effective than the whole-cell vaccine (85 per cent efficacy versus 48 per cent). The two-component vaccine (which did not contain pertactin) was not as effective as the five-component acellular vaccine. This result demonstrates the importance of pertactin as an integral component of acellular pertussis vaccines. Since 1991, SB has been focusing on its three-component vaccine Infanrix, which includes pertactin, both for DTPa and in combination with hepatitis B, Haemophilus influenzae type b (Hib) and polio.

It appears that pertactin is an important addition to the performance of the vaccines in these studies as the only vaccines demonstrating efficacy contained pertactin. SB is the exclusive worldwide licence holder from Evans Medical (a wholly-owned subsidiary of Medeva) of the pertactin component.

Conducted under epidemic conditions, the NIAID study in Italy shows that Infanrix was protective against pertussis. It confirms an SB German household contact study, presented at ICAAC (Interscience Congress for Antimicrobial Agents and Chemotherapy) in October 1994, which showed that Infanrix protected 9 out of 10 vaccinees.

SB's Infanrix, the only acellular pertussis vaccine in the NIAID studies approved for primary vaccination, was cleared for marketing in Germany in March 1995. Registration has been applied for in 11 countries. Infanrix is also licensed in Germany as a booster dose for children vaccinated with either whole-cell or acellular pertussis DTP vaccines.

Pertussis, commonly known as 'whooping cough', is a serious disease. Each year, there are about 50 million cases worldwide leading to an estimated 350,000 deaths. Vaccination against diphtheria, tetanus and pertussis is recommended by the World Health Organisation and the US Centres for Disease Control and Prevention as well as most governments worldwide.

Childhood vaccinations are a central feature of healthcare strategies around the world and SB is committed to developing combined paediatric vaccines to prevent a wide array of infections affecting children. SB has filed its first combined vaccine based on DTPa with Haemophilus influenzae type b (Hib). Phase III clinical trials are ongoing for a number of DTPa combined vaccines to protect against hepatitis B, Hib and polio.

SmithKline Beecham is one of the world's leading vaccine manufacturers. Each year, SB distributes about 550 million doses of vaccines in more than 175 countries. The company continues its commitment to the discovery, development and worldwide distribution of innovative paediatric vaccines.

In addition to vaccines, SmithKline Beecham discovers, develops, manufactures and markets pharmaceuticals, over-the-counter medicines, health-related consumer products and clinical laboratory testing services.

 

In announcing the results of two landmark, placebo-controlled efficacy studies for pertussis (whooping cough) vaccines, the United States National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID) has clearly demonstrated that acellular pertussis vaccines are highly effective and much less reactogenic than the current whole-cell pertussis vaccines in providing protection for infants around the world. Pertussis, also known as whooping cough, is a highly contagious bacterial infection that causes violent coughing spells that make it difficult for an infant to eat, drink or even breathe.

Both studies began in 1992 and together enrolled more than 25,000 children. They were designed to investigate a new type of pertussis vaccine - acellular pertussis. One study was conducted in Sweden; the other in Italy. They coincided with severe pertussis epidemics in both countries. Until these studies, only limited data on the efficacy and safety of acellular vaccines in infants were available.

In most countries, the classical whole-cell pertussis vaccines have been effective in reducing the incidence of pertussis, but they have been linked to a number of side effects such as fever and local reactions at the injection site and fretfulness.

The NIAID selected Sweden and Italy for these studies because in these countries pertussis vaccination is not compulsory and large populations of unvaccinated children are at risk for pertussis. Because of the widespread use of DTP vaccination in the United States, the number of cases of pertussis occurring there is so small as to make a definitive efficacy trial impossible to perform.

The concept behind acellular pertussis vaccines is to take the parts of the whole-cell bacteria, which are believed to provide the protective efficacy of the vaccine, and to leave out those which may cause side effects. The acellular vaccines have been shown to have fewer side-effects than whole-cell pertussis vaccines, but until now the acellular had not been tested for safety and efficacy against whole-cell vaccines in large, well-controlled clinical trials.

ITALIAN STUDY

This study began in September 1992 at 62 sites in four regions in Italy. A total of 15,601 children were vaccinated with one of four vaccines: either one of two acellular pertussis vaccines (DTPa), a whole-cell pertussis vaccine (DTPw) or a diphtheria and tetanus (DT) vaccine without the pertussis component. The average duration of follow-up after the third dose was 17.2 months.

The vaccines used in the trial were:

· SmithKline Beecham: Infanrix, a three-component DTPa vaccine containing PT, FHA and pertactin*

· Biocine-Sclavo: three-component DTPa vaccine containing PT, FHA and pertactin*

· Connaught Laboratories Inc: DTPw vaccine

· Biocine-Sclavo: DT vaccine

The study objective for demonstrating effectiveness was an efficacy rate of more than 80 per cent. According to these criteria, both Infanrix and the Biocine DTPa vaccine were effective, with no significant difference between them. The whole-cell vaccine was less effective. The actual efficacy data are summarised in Table 1.

Both Infanrix and the Biocine vaccine had significantly fewer side effects than the whole-cell vaccine.

SWEDISH STUDY

This study began in March 1992 at 14 sites in Sweden. A total of 9,829 children were vaccinated with either one of two acellular pertussis vaccines (DTPa), a whole-cell pertussis vaccine (DTPw) or a diphtheria and tetanus (DT) vaccine without the pertussis component. The families were followed for two years after the third dose.

The vaccines used in the trial were:

· SmithKline Beecham: a two-component DTPa vaccine containing pertussis toxoid (PT) and filamentous haemagglutinin (FHA)

· Pasteur-Mérieux-Connaught: a five-component DTPa vaccine containing PT, FHA, pertactin* and agglutinogens 2 and 3

· Connaught Laboratories Inc: DTPw vaccine

· Swedish Bacteriological Laboratories: DT vaccine

The study objective for demonstrating effectiveness was an efficacy rate of more than 80 per cent. According to these criteria, the Pasteur-Mérieux-Connaught DTPa vaccine was effective; the SB two-component DTPa vaccine and the Connaught Laboratories DTPw vaccine did not fulfil the pre-set efficacy criteria. The actual efficacy data are summarised in Table 1.

Both the Pasteur-Mérieux-Connaught DTPa vaccine and the SB two-component vaccine had significantly fewer side effects than the whole-cell vaccine.

 

Table 1

Vaccine

Manufacturer

Number of components

Contained pertactin?

Efficacy

INFANRIX

SB

Three

Yes

84%

DTPa

Biocine-Sclavo

Three

Yes

84%

DTPa

Pasteur-Mérieux-Connaught

Five

Yes

85%

DTPa

SB

Two

No

58%

DTPw

Connaught

Whole-cell

N/A

36% (Italian study)

48% (Swedish study)

 

Based on this data, scientists predict that acellular vaccines will become the cornerstone of new combination vaccines that will require fewer doses and will protect children against numerous diseases.

*SB is the worldwide exclusive licence holder (from Evans Medical) for pertactin.

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Posted: July 2004

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