New Biopharmaceutical Entities in 2006
New biopharmaceutical entities (NBEs) are defined as products involving novel biopharmaceutical active ingredients not substantially similar to previously approved products. These new products usually have active ingredients with novel identity/sources, methods of manufacture, and specifications. Five of the seven first-half 2006 approvals were NBEs.
~ Gardasil, and HPV vaccine from Merck (www.merck.com), has been widely hailed as the first vaccine for prevention of oncogenic virus-associated cancer, in this case cervical cancer (but many consider hepatitis B virus vaccines, which first became available in the 1980s, to be the first vaccines for cancer prophylaxis, in this case hepatocarcinoma).
Gardasil is a quadrivalent (tetravalent; four antigen) human HPV vaccine containing recombinant HPV L1 protein virus-like particles from HPV types 6, 11, 16, and 18 expressed by a transformed Saccharomyces cerevisiae (yeast) cell line complexed with a conventional aluminum adjuvant.
This range of HPV antigens is designed to provide protection against most cervical cancer (primarily due to HPV types 16 and 18) and genital warts (primarily due to HPV types 6 and 11). This vaccine is optimally used in prepubescent females (and also males) before HPV-infection due to sexual activity. It will be interesting to see how Merck markets this vaccine, as many social conservatives are against required pediatric use, alleging that this would encourage sexual promiscuity.
~Myozyme, from Genzyme (www.genzyme.com), is a formulation of recombinant glycosylated alpha glucosidase enzyme, which degrades glycogen, expressed by CHO cells. Myozyme is the first treatment available for patients with Pompe disease, a lysosomal storage disease involving accumulation of incompletely degraded glycogen in the lysosomes of cells.
~RotaTeq, a rotavirus vaccine from Merck, is a formulation of five live bovine/human reassortant (natural recombinant) rotavirus strains cultured in VERO cells, a continuous African green monkey kidney cell line, used as an oral vaccine for prevention of pediatric rotavirus disease. Another rotavirus vaccine, RotaShield from Wyeth (www.wyeth.com), previously received FDA approval, but was composed of fully human reassortant virus and was taken off the market due to rare, but serious, adverse effects
~Pfizer's (www.pfizer.com) Exubera is an inhalable dry powder, rapid-acting formulation of recombinant insulin expressed by transformed E. coli bacteria stabilized in ~1-micron glass-stabilized particles using mannitol as an inert amorphous glass-like matrix. The insulin is essentially the same as in other nonmodified insulin products, but the modification of insulin by physical encapsulation confers substantially different pharmacokinetic properties.
~Lucentis from Genentech (www.gene.com) is a recombinant Fab fragment of a humanized murine monoclonal antibody expressed in E. coli bacteria with binding specificity for vascular endothelial growth factor (VEGF).
Lucentis is an anti-angiogenesis agent and reportedly the first therapeutic with the ability to reverse wet, the most common type, of age-related macular degeneration (AMD).
Genentech has priced this at nearly $2,000/vial or injection (>$10,000/year). However, one of Genentech's own products, Avastin, a full-sized recombinant VEGF monoclonal antibody approved for cancer treatment, may cannibalize sales of Lucentis. Anecdotal reports involving thousands of patients treated with low-dose Avastin, costing <$20/dose, indicate that this is also safe and effective for wet AMD. Genentech has no plans to test and seek approval of Avastin for wet AMD. It remains to be seen whether physicians and insurers, potentially facing liability and malpractice suits, will use Lucentis or adopt cheaper Avastin off-label.