Biopharmecuticals: Approval Trends in 2006 - Thirteen biopharmaceuticals gained marketing authorization - BioPharm International


Biopharmecuticals: Approval Trends in 2006
Thirteen biopharmaceuticals gained marketing authorization

BioPharm International
Volume 21, Issue 9

While the exact underlining causes of multiple sclerosis remain to be elucidated, the condition is believed to be an autoimmune one, in which selected immune system cells (leukocytes) attack the central nervous system. Tysabri therefore may work by blocking migration of such leukocytes across the blood-brain barrier (comprising endothelial cells lining brain capillaries), and hence preventing them from damaging the neuronal tissue.

Two major clinical studies (each two years in duration) were undertaken, one using Tysabri as a monotherapy and the other involving its use in combination with interferon. Both showed clear benefit in the context of MS. In the monotherapy trial, for example, Tysabri treatment reduced the percentage of patients experiencing a sustained increase in disability from 29% to 17% and increased the number of patients remaining relapse free from 41% to 67%. The most common side effects noted in the studies included an increase in general infection rate, rash, headache, dizziness, fever, and fatigue. The increased risk of infections, particularly PML, means the product should not be administered to those already particularly prone to acquiring an infection (e.g., immunocompromised individuals), to those who have cancer or who are also receiving other long term MS drugs (interferon or glatiramer acetate), or who are under 18 years of age.

The product is manufactured by Biogen Idec (Cambridge, MA) and distributed by Elan in both the US and EU.

Valtropin (somatropin) is a recombinant form of human growth hormone (hGH) produced in S. cerevisiae. It is a nonglycosylated, single-chain 22 kDa, 191 amino acid polypeptide of identical sequence to that of native hGH. It gained approval in the EU in April 2006 and, like Omnitrope (see above), is classified as a biosimiliar medicinal product. Valtropin is indicated for the treatment of children with growth failure or reduced growth rates because of either inadequate secretion of endogenous growth hormone, Turner syndrome, or chronic renal insufficiency. It is also indicated for use in adults displaying growth hormone deficiency.

After initial fermentation of the producer yeast cells, the crude product is purified via multiple chromatographic steps. Glycine, mannitol, and sodium phosphate buffer constituents are added as excipients. The final product is then lyophilized, with each vial containing 5 mg (equivalent to 15 IU) of active ingredient. A prefilled syringe containing reconstituting solution (1.5 mL WFI containing 0.3% M cresol) is also supplied. The reconstituted product is for repeat use as a multidose product. Dosage is individualized for each patient and administration involves a daily subcutaneous injection.

The reference medicine chosen with which to compare Valtropin was Humatrope, a recombinant hGH available in the EU since 1990. The indications are the same for both medicines and trials showed them both to have similar safety and efficacy profiles. The main clinical study supporting approval entailed treatment of 149 children with either Valtropin or Humatrope over a 12-month period. Similar increases in height gain and speed of growth were recorded (11.4 and 10.5 cm/year, respectively) and the most common side effects noted for both were mild edema and transient local skin reactions.

The biologically active substance is manufactured by LG Life Sciences (Joenbuk-do, South Korea) and BioPartners (Russelsheim, Germany) holds the European marketing authorization.

Vectibix (panitumumab) is a 147 kDa human IgG 2 kappa monoclonal antibody produced by recombinant means in a CHO cell line. The product, which binds to the human epidermal growth factor receptor (EGFR), was approved in 2006 in the US and is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma.

The EGFR is a transmembrane glycosylated protein. It is constitutively expressed in many normal cell or tissue types, including those of the skin and hair follicle. Its overexpression is, however, linked to various cancers including colorectal cancer. Binding of receptor ligands (EGF and transforming growth factor-α) triggers signal transduction, which results in activation via phosphorylation of various intracellular protein tyrosine kinases. These, in turn, regulate transcription of various gene products that promote cell growth, proliferation, and transformation. Vectibix, by binding to the EGFR, competitively inhibits binding of native ligand to the receptor without itself triggering signal transduction. The growth of target cells is thereby inhibited and apoptosis is usually triggered.

The manufacturing process of Vectibix involves recovery subsequent to cell culture, followed by multiple chromatographic purification steps. Sodium chloride and sodium acetate are added as excipients and the final filter-sterilized product is formulated as a liquid intended for intravenous (IV) infusion, with the active ingredient present at a concentration of 20 mg/mL. Recommended dosage entails infusion of 6 mg active/kg over 60–90 minutes once every 14 days. The elimination half life of the product is approximately 7.5 days.

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