The Re-emergence of Peptides
Formulation is also key to drugs or entire drug classes. The re-emergence of peptide drugs, after a 15-year lull due to delivery difficulties, illustrates how much bio-drugs rely on formulation strategies.
Much has been written on the importance of parenteral products and the rise of biotech. As critical as the injectible/infusion route may be, companies are always looking to improve delivery routes and perhaps reduce the need for injection. Pfizer’s(www.pfizer.com) Exubera® inhalable insulin powder is an obvious success story.
One of the biggest boosters of peptide drugs using novel formulations has been Unigene (www.unigene.com) CEO, Warren Levy, Ph.D. “Formulation is the key to peptide delivery,” says Dr. Levy. He notes that companies are investigating nasal, oral, inhalable, and even transdermal peptide delivery. Although the chemical composition of peptides presents challenges to formulation-delivery strategies, Dr. Levy believes that, as with small molecule drugs, the oral route is highly preferable.
Unigene has demonstrated that oral delivery is possible with peptides through enterically coated tablets or capsules that protect ingredients from proteolytic enzymes in the gut. The key ingredients are an organic acid that temporarily inactivates digestive enzymes and a detergent that transiently opens up tight junctions in the digestive tract, allowing small peptides to enter the system through the stomach.
The company has had a hand, through application of its high-yield peptide expression and nasal delivery technologies, in the success of Fortical® nasal calcitonin spray. Unigene has also licensed technology to GlaxoSmithKline (www.gsk.com) for an oral formulation of parathyroid hormone and is working through a supply agreement with Novartis (www.novartis.com) on that firm’s development-stage calcitonin product.
Novozymes Delta Ltd (www.biopharmaceuticals.novozymes.com) develops and manufactures recombinant protein products using Saccharomyces cerevisiae and licenses its yeast-based expression system to pharmaceutical, healthcare, and biotech partners. The company, which was formerly known as Delta Biotechnology, offers products that include yeast-derived recombinant human albumin (Recombumin(R), a protein stabilizer, and recombinant human transferrin (DeltaFerrin(tm), which assists in critical iron uptake in protein-producing cells. Merck & Co. (www.merck.com) uses the recombinant albumin product Recombumin(R) in formulating its M-M-R(R)-II (measles, mumps, rubella) human vaccine to replace serum-derived albumin. Novozymes Delta plans to launch its transferrin product in May.
Advantages of recombinant, versus human-derived albumin, are numerous; improved quality and consistency are the most significant from a manufacturing perspective. Since the product cannot pass on animal diseases, products formulated with it are safer and less likely to experience recall.
Regulatory bodies were particularly cautious about Recombumin since it is a recombinant protein and makes up a significant fraction of the delivered drug. Novozymes Delta Ltdtherefore conducted a large Phase I evaluation of the protein’s safety and tolerability. Novozymes Delta Ltd's regulatory submissions included a drug master file and a safety/tolerability package.
No clinical data needs to be submitted for the transferrin product because it is not delivered to patients.