Status: FDA filing withdrawn; formerly approved in EU

Organizations involved:

Chiron S.p.A. – Manuf.; R&D; Tech.; Europe mark.; Former

Chiron Corp. – Parent; Former

Evans Vaccines Ltd. – Patent dispute

Cross ref: See the entry (#236) for the recombinant per-tussis toxin vaccine component of this vaccine in the Recombinant DNA Products section. See the entry for Pertussis Vaccines, Acellular (#506), and Diphtheria and Pertussis Toxoids and Pertussis Vaccine (DTP/DTaP) Products (#429). See the entries for Tetanus Toxoid Products (#543); and Diphtheria Toxoid Products (#418). See also entries for entries for this vaccine’s component diphtheria and tetanus toxoids.

Description: Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed or Pertugen is a DTaP vaccine from Chiron Corp. (merged into Novartis AG in spring 2006) containing conventional diphtheria and tetanus toxoids, with the pertussis component containing conventional purified filamentous hemagglutinin (FHA) and pertactin (69 kDa protein), plus recombinant pertussis toxin which has been dotoxified/inactivated (to toxoid) by recombinant DNA methods (e.g., sequence deletions).

Nomenclature: DTaP Vaccine/Chiron [BIO]; Pertugen [TR U.S.; no plans for use]; Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed [FDA unofficial; not FDA approved]; Triacelluvax [TR in European Union except Germany]; DTPa [CDC]; DTaP3-CB [SY]

Companies.: The vaccine was developed, manufactured and marketed by Chiron S.p.A. (Chiron Vaccines), CBER/FDA est. no. 1222, a subsidiary of Chiron Corp. (which has now been merged into Novartis AG).

FDA class: Biologic PLA

Status: Chiron Corp. filed a PLA for FDA approval of Pertugen on Oct. 1, 1996, and voluntarily withdrew this application on Feb. 2, 1999. The company cited competitive reasons. With four DTaP vaccines then in the U.S. market and Chiron then having only seven vaccine sales reps in the U.S. (handling its rabies vaccine), the company decided to concentrate on its plans for marketing in Europe, where the company had about 300 sales reps.

The vaccine received its first approval in Italy in Dec. 1994. European Union approval of Triacelluvax was granted on Jan. 11, 1999. However, the vaccine was only ever marketed in Italy. On March 7, 2002 , Biocine/Chiron voluntarily withdrew its European Union approval.

Tech. transfer: In March 1998, Chiron won a European patent dispute brought by Evans Medical, then recently acquired by Powder-Ject Pharmaceuticals plc (later acquired by Chiron), resulting in revocation of Evans’/Medeva’s European Patent 0-162,639 concerning pertactin. Evans/Medeva had alleged that Triacelluvax infringed this patent. Evans/Medeva had exclusively licensed pertactin and other pertussis vaccine technology to SmithKline Beecham S.A., now GlaxoSmithKline, for use in Infanrix (#433). Chiron (now Novartis), presumably, received royalties from sales of Infanrix.

Trials: Pertugen, like other DTaP vaccines, induces protective immunity against diphtheria and tetanus, and variable immune responses to its different pertussis antigen components. In clinical studies, antibody responses to pertussis toxin were normally higher with Pertugen than with other combination vaccines containing a pertussis vaccine component. Pertugen was at least as efficacious as most whole cell pertussis vaccines and was similar in efficacy to the most efficacious acellular pertussis vaccines containing 3 or more pertussis antigens.

A pivotal clinical trial conducted in Italy in 15,601 infants comparing a whole-cell pertussis component DTP vaccine (from Sanofi Pasteur), a chemically detoxified acellular pertussis component DTaP vaccine (Certiva), and Triacelluvax (Pertugen) DTaP was reported in the Feb. 8, 1996 issue of the New England Journal of Medicine. Both DTaP vaccines resulted in fewer adverse effects, and Triacelluvax was more than twice as effective than the whole-cell DTP vaccine.