Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please can you give a brief introduction to the half-life of drugs?
A drug's half-life indicates how long a substance will remain active in the body. It is essentially the period of time that it takes for the concentration of the amount of the drug to be reduced by half, and therefore, determines how frequently a drug needs to be administered to maintain its therapeutic effect.
Put simply, the shorter the half-life of a drug, the quicker it is eliminated from the body and the more often the drug has to be taken or injected by patients to ensure a sustained impact.
Why is it advantageous to extend drug half-life?
In the development of new drugs, obstacles are often encountered with the short therapeutic half-lives of many peptides and proteins. Rapid clearance from the body makes it necessary to deliver higher doses more frequently in order to achieve efficacy.
The extension of half-life reduces the frequency of injections needed to provide therapeutic benefit. This makes compliance less complicated for the patient and that translates into better quality of life.
What are the main challenges in extending the half-life of drugs?
The main challenge in extending the half-life of drugs is the development of safe, versatile and regulatory compliant technologies that enable medicine levels to be maintained in the bloodstream and avoid the degradation mechanisms that prey upon biologic therapies.
The industry is increasingly requiring more advanced technologies that enable greater control over the half-life of drug candidates and allow developers to tailor the period of time a drug remains active to meet the specific needs of individual medical conditions.
For some half-life extension technologies ease of manufacture can be a challenge. The use of the Veltis option gives drug developers access to a system that is based on Novozymes’ decades-long experience of manufacturing recombinant albumin at commercial scale.
Alternatively drug developers can choose to make Veltis-albumin fusions in animal cells or other microbial systems not offered by Novozymes.
Further, our customers can also choose to conjugate their drug to Veltis albumins if they prefer to stick to their existing manufacturing process for their own API peptide or protein candidate.
Please can you outline Novozyme’s Veltis technology? How does this work?
Veltis is an albumin-based half-life extension technology for proteins and peptides that enables drug developers to define how long their drug candidate is therapeutically active in the body, and, as a result, enables dosage size and frequency to be tailored to offer improved therapeutic impact.
Through using the Veltis technology in the design of drugs, developers can now modify the half-life of their products to provide weekly, two-weekly, or even monthly dosing, while enhancing drug tolerability and efficacy.
As a result, manufacturers can flexibly tune their drug design with the required characteristics that provide a competitive edge and optimum effect.
The technology is most applicable to peptide and protein drugs used to treat chronic conditions where patients self-administer such as diabetes, hemophilia or neutropenia, while the platform can also be exploited for small molecules in oncology.
How was Veltis developed?
The science behind Veltis exploits Novozymes' world leading research into the interaction of albumin and its natural cell surface receptor which substantially accounts for the native protein's 19 day half-life.
We have engineered a range of albumin variants with increased binding to the human FcRn receptor and have demonstrated that this increase in receptor binding correlates directly with an increased in vivo half-life.
The combination of a drug candidate with our albumin variants allows for longer acting therapeutics than was previously possible using other half-life extension techniques.
What impact do you think this technology will have on drug development and patients’ lives?
The coupling of the Veltis technology with drug candidates results in products that are not only superior therapeutically, but that are preferred by patients due to their capability to improve quality of life by reducing the inconvenience of the daily or twice daily dosing regimens that are associated with some chronic medical conditions.
As the technology is based on the natural blood protein albumin serving as the drug carrier, it also represents a highly soluble, non-immunogenic, bio-compatible technology that offers a strong safety profile and low risk of adverse effects in patients.
What are the current limitations of Veltis?
Due to limitations of E coli in protein expression in relation to the production of proteins with disulphide bonds, Veltis is not suited to manufacture in this host.
What are Novozymes Biopharma’s plans for the future?
We believe that we have a very innovative half-life extension technology which allows our partners including GlaxoSmithKline, Janssen and other pharmaceutical companies to develop better and longer lasting drugs.
We believe this and our other agreements will pave the way for greater understanding and awareness of the potential of Veltis in the future with the aim of seeing increasing numbers of feasibility studies taking place for a broad scope of drug candidates.
Where can readers find more information?
To find out more information about optimising drug designs using Veltis, please visit www.veltis.novozymes.com
About Dermot Pearson
Dermot Pearson is Strategic Marketing Director with Novozymes Biopharma UK with responsibility for market development of the company’s Veltis half-life extension and drug targeting business.
His role includes overseeing product development, branding, and pricing, and life cycle management, all on global basis. A member of the company's business unit management team, Dermot has held past roles in R&D, Quality and GMP Product Manufacturing.