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Peptide Process Chemistry – A New Era?

Facilities Research and DevelopmentSince pioneers such as Bodanszky and Du Vigneaud first produced them synthetically in the 1950’s, peptides have always held tremendous – but unrealized – promise for human health. Despite their potential, both production and delivery mechanism limitations had traditionally held back commercialization.

Some of the historic limitations of peptide drugs have been:

  • Peptides require complex chemistry – rendering them expensive and difficult to manufacture
  • They possess a very short half-life, complicating administration
  • Peptides have traditionally suffered from a lack of oral availability

Over the years, these limitations (among others) have tended to lead pharma away from peptide drug development in favor of more patient- and bottom-line – friendly alternatives (namely, small molecules delivered as pills).

But things are definitely changing for peptide therapeutics.

Enter the Peptide Era?
There have been a number of prognostications that peptides are the next big pharma wave. As a peptide API manufacturer, we’re a bit more guarded in our expectations. Yes, the potential of peptide-based drugs is enormous. Yes, there have also been plenty of technical limitations to overcome. The good news – lots of those limitations are being overcome as peptide science continues to advance.

The Advantages of Peptides
In spite of development hurdles, interest in peptides has never really waned…and in fact, continues to grow. According to one market report,  the peptide therapeutic market is projected to grow to more than $25 billion over the next 3 years. A few years back, there were 60 approved peptide drugs, with 600+ in development (a number that has undoubtedly grown).

But why peptides? What makes them so compelling?
A couple of things stand out:

  • Peptides are naturally-occurring, and tend to possess very robust and well-characterized safety profiles
  • Peptides tend to have greater specificity than small molecule drugs
  • Peptide drugs tend to receive FDA approval at a significantly higher rate than small molecule drugs (I’ve seen a 20% versus 10% approval rate for peptides).

Peptide Chain Length
Some of the most important advances have occurred in the production of larger peptides. Chains are getting longer and more complex. Drugs like Fuzeon, with 36 amino acids, proved the feasibility of large scale peptide manufacturing. Using solid phase synthesis (SPPS), sequences of 100 amino acids or longer are no longer outside the realm of reality. Deaggregation strategies, conjugation, PEGylation and other techniques have all intersected – creating an ever-widening range of opportunities for peptide therapeutics. This is evident in the growing list of potential clinical applications – from Alzheimer’s disease and oncology to metabolic disorders and cardiovascular disease (a focus of ours here at Neuland) ….and beyond.

Wider Range of Delivery Options
Once confined to the realm of injectables, recent advances have allowed for transdermal, oral and nasal delivery of peptides. While these delivery mechanisms for peptides are formulated on a case-by-case basis (and don’t apply to all peptides generally, the very fact that we’re discussing oral or transdermal peptide drugs is a sign of tremendous progress over just the last ten years.

Some Limitations for Peptide Therapeutics
There remain some hurdles to overcome, including lack of regulatory clarity for peptide-based drugs. Given their relatively recent emergence, regulatory frameworks will need to play catch up – something we’re seeing happen with genotoxic impurity standards (see our earlier post, Are Genotoxic Impurity Standards Too Weak?)

Peptide drugs will undoubtedly play an increasingly prominent role in medicine over the coming decade or two. In the near-term, this will likely play out in the field of oncology where peptides have an established presence. As economies of scale continue to improve – and innovations in drug delivery open up new horizons – the number of therapeutic roles peptides play will expand.

 

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