Ratiopharm unit plans improved biologic drug

Pegylation is used to extend a therapeutic protein's half-life - the time required for half the quantity of a drug to be metabolised or eliminated by normal biological processes - by attaching polyethylene glycol or 'peg' polymers to the drugs.

The process increases the size of the molecule and keeps it circulating in the body and exerting its effects for a longer period of time. A number of biologic drugs - including interferon alpha for hepatitis, erythropoietin for anaemia, the white blood cell stimulator filgrastim (G-CSF) for neutropenia and human growth hormone - are already available in pegylated formulations that require less frequent dosing than their unmodified counterparts.

However, not all protein-based drugs are suitable for linking to peg, and Neose has developed a new method of linking the polymer to carbohydrate (glycan) groups on the protein, expanding the range of drugs that can be modified in this way.

BioGenerix is part of the leading German generics group Ratiopharm, and as its name suggests is involved in the development of new versions of already-approved biologic drugs.

The market for biogenerics - known by regulators as 'biosimilars' in Europe and 'follow-on biologic drugs' in the US - has been held back by difficulties in demonstrating that the copies behave in the same way - i.e. they are bioequivalent - to the original brandname drugs.

While considerable progress has been made in mapping out a regulatory route to market for these generics, none has yet reached the market in either Europe or the US, as regulators and industry have been unable to agree on how to demonstrate bioequivalence. To date, all the biologic drugs on the market have had to undergo rigorous, time-consuming and costly clinical tests to prove safety and efficacy. Bioequivalence studies would bypass a lot of that work.

BioGenerix acknowledges these difficulties and has developed its own strategy to develop what it calls 'multisource proteins'.

Rather than relying on regulators to map out the requirements for bioequivalence, the company's strategy is to take on more development risk and costs in the project, with the aim of developing improved, rather than equivalent versions of biologics.

The agreement with Neose is an example of this type of approach, and could yield a product that can be differentiated from competitors should the market for the active protein become generic.

Moreover, pegylation also appears to only affect pharmacokinetic parameters and has not modulated the safety or efficacy of drugs, and adding peg groups may actually decrease immunogenicity because the polymer itself is not immunogenic and shields the protein therapeutic from recognition by immune cells and antibodies.

This has led to speculation that biogenerics based on pegylation may qualify for less rigorous approval requirements, although observers have pointed out that this relaxed threshold for pegylated generics could have implications for the approval of new drugs which differ from an in vivo​ protein only by the addition of the polymer.

BioGenerix is not yet divulging the identity of the protein, but is already woking on developing biologic treatments for anaemia, multiple sclerosis (currently treated with interferon beta) and neutropenia.