From The Editor

Albumin Addresses Need For Better And Longer-Lasting Drugs

By Ed Miseta, Chief Editor, Outsourced Pharma and Clinical Leader
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Miseta

A recent article in the Wall Street Journal addressed the most recent research and technologies in pharma that are making drugs more efficient. One protein that is leading the advancements in this area is albumin.  

The albumin developed by Novozymes makes it possible to produce better and longer lasting drugs. The development started more than 20 years ago in Nottingham, UK, when the Bass Brewery was seeking novel ways to generate value from its waste yeast. To do so, it established a company to assess the feasibility of making albumin from brewer’s yeast. The brewery eventually sold off the company, and Novozymes has since acquired the technology. Novozymes now produces albumin for a number of pharmaceutical companies, although the process currently uses a more efficient yeast developed by Novozymes rather than brewer’s yeast.

More recently, Novozymes has announced a series of collaborations within this field, with Janssen, GlaxoSmithKline, and more. One result of this collaboration is the FDA approving GlaxoSmithKline’s new type 2 diabetes drug Tanzeum/Eperzan. The drug relies on new technology that allows patients to inject once-weekly instead of daily.

Dr. Darrell Sleep, Director of the Molecular Biology and Fermentation department, Novozymes Biopharma

Dr. Darrell Sleep, who holds a degree in Biochemistry from the University of Leeds in the U.K. and a Ph.D. in Molecular Development from the University of Edinburgh, has authored over 30 publications and patent families, centered on the development of biopharmaceutical products, technologies and processes. He is currently Director of the Molecular Biology and Fermentation department at Novozymes Biopharma, a research team engaged in the continuous improvement of efficient yeast systems for the manufacture of recombinant native and bioengineered peptides and proteins. Amongst others, Dr. Sleep’s team has developed processes for the production of recombinant human albumin, albumin fusions, antibody fragments and engineered albumins with improved biopharmaceutical properties. Current research is aimed at improving the stability and extending the circulatory half-life of peptides and proteins through formulation, conjugation and genetic fusion to albumin.

I recently spoke with Dr. Sleep about albumin and the promise it holds for the pharma and biopharma industries.

Ed Miseta: Can you tell me about the recent collaboration with pharmaceutical companies with regards to the albumin results for type 2 diabetes?

Dr. Darrell Sleep: We have worked in the past with GlaxoSmithKline to support their development of the technology. In fact they have done all of the drug development and manufacturing work. We continue to work with other companies to provide technical and regulatory support for their drug development efforts in type 2 diabetes as well.

The first generation Veltis® technology has previously been licensed to GSK and CSL Behring. GSK have developed an albumin fusion to GLP-1 for use in the diabetes field. The GLP-1 albumin fusion is manufactured using the same yeast expression system Novozymes Biopharma developed to manufacture its internal native sequence product Recombumin® Prime. The GLP-1 albumin fusion, which has the name albiglutide, has been approved for use in Type 2 diabetes where it will be marketed in Europe under the trade name of Eperzan and in the USA under the trade name of Tanzeum. Novozymes has also announced a research agreement with EpiVax in a press release dated 12th February 2013. The research agreement will involve linking EpiVax’s proprietary Tregitope (T regulatory epitopes) immune-modulating therapy for the treatment of Type 1 diabetes, to Novozymes’ proven Veltis® half-life extension platform, helping to enhance its pharmacokinetic and pharmacodynamics properties. As a result, it will be possible to modulate half-life of the therapy to offer improved control, enhancing the overall efficacy of treatment.

Miseta: What can you tell us about the Veltis® technology?

Sleep: The Veltis® technology is based on a series of wild-type and engineered albumins designed to interact in a modified way with the natural endothelial receptor for albumin.

Human albumin is the most abundant human blood plasma protein. Human albumin also has an extraordinarily long circulatory half-life, which means it survives in the human body for a very long time, in this case almost three weeks. Many of the protein and peptide drugs currently being developed for human therapeutic intervention have a circulatory half-life measured in minutes or hours. As a consequence the drugs have to be administered frequently, often daily, which is not patient friendly due to the high number of administrations. Albumin’s long circulatory half-life is in part due to its interaction with the FcRn receptor found predominantly on endothelial cells. Novozymes has characterized the interaction of albumin with FcRn and through this knowledge has engineered the albumin to modify the albumin-FcRn interaction. By the use of the Veltis® engineered albumins, the new technology opens up the opportunity to optimize drug dosing regimens to once weekly, once every two weeks, or even once monthly.

Miseta: What are some of the specific products?

Sleep: Some products that our customers are working with include GLP-1, but in addition CSL is using the technology to improve coagulation factors such as FVII. Recently CSL has published clinical data on a Veltis® albumin fusion to a coagulation factor called FIX. The product is called rIX-FP. Editor’s note – See a press release on this announcement here: New Findings Support Less Frequent Dosing in Hemophilia B Patients Treated with Coagulation Factor IX with Recombinant Albumin (rIX-FP).  

In addition Teva has exploited the technology for their version of filigrastim, which is used to boost white blood cell production in patients undergoing cancer treatment. The innovative immunology company EpiVax is also evaluating Veltis® for being able to develop deliverable forms of their tregepitopes for treatment of a variety of immune diseases.

Miseta: How have the recent collaborations helped with this technology?

Sleep: Novozymes input to the application of the technology helps our customers to more quickly refine the process development and manufacturing of the drug. In addition, some of our customers use our expertise to select the Veltis® variants best suited to achieve the desired improvements in the drug that they are seeking.

The recent approval in the U.S. and Europe for albiglutide has demonstrated that there is a clear regulatory path to the approval of drugs employing the 1st generation Veltis® technology, which make use of the native sequence albumin to extend the circulatory half-life of the GLP-1 drug genetically fused to the albumin. The progress of CSL’s FIX-albumin fusion also demonstrates that complicated proteins, as opposed to smaller peptides such as GLP-1, can also significantly benefit from the Veltis® technology. The recently announced collaborations with Janssen and EpiVax to evaluate the Veltis® engineered albumins to further improve the drug dosing validates the need in the market place for improved drugs with optimized drug profiles

Miseta: How does this affect the delivery of the drug?

Sleep: Veltis® albumins typically extend the half-life of peptide and protein drugs and thus enable patients to require fewer injections – once a week or possibly once a month, depending on the drug. We also believe that Veltis® may be applied to some small molecule anti-cancer or rheumatoid arthritis drugs to target them to the site of action and thereby making them more effective.

Miseta: Anything else about this technology that my readers may want to know?

Sleep: In addition to being able to readily work on Veltis® by genetic fusion, Novozymes has forged a number of partnerships with chemistry companies to be able to apply Veltis® by conjugation to peptides and small molecules.  We believe that there may be a very exciting use of albumins in the delivery of small molecule drugs to the sites of solid tumors; the recently-announced partnerships with Almac and ThioLogics will help us deliver a well-rounded offer to drug developers in this space by allowing us to combine our protein design and manufacturing expertise with chemical coupling of drugs to albumin and their subsequent scale-up and production during the drug development process.

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