Better biogenerics

Controlled Therapeutics (Scotland) has been awarded a UK grant to develop a technology that could be used to create sustained-release versions of generic peptide and protein drugs without the need to conduct extensive registration trials.

The polymer-based system uses a hydrogel matrix to carry the active molecule but does not alter it chemically. In this respect, it differs significantly from PEGylation - the most widely-used controlled-release technology for biological drugs - which requires chemical attachment of the drug molecule to the polyethylene glycol (PEG) polymer.

Attachment of PEG to a molecule leads to an extension of its half-life in the body, and in turn requires less frequent dosing. For example, Amgen's Neupogen (filgrastim) is used in cancer patients to support their immune function after treatment with cytotoxic drugs. In its initial form, the drug required daily injections for up to two weeks. Amgen has since developed a PEGylated version of the molecule Neulasta (pegfilgrastim), that can be delivered as a single dose each chemotherapy cycle, typically once every three weeks.

However, to get approval for Neulasta, Amgen had to go back through the entire clinical trials process, as regulatory authorities considered that the new drug was a New Chemical Entity (NCE) requiring a full registration package. The hope is that using CTS' hydrogel technology could circumvent this requirement and provide a simplified route to approval, although just how this may be achieved will require extensive negotiation with regulatory authorities.

The technology would be of benefit not only for companies developing new biological drugs, but also those working on generic versions of existing biologicals that want to differentiate their products in the marketplace with a more favourable dosing regimen.

Biodegradeable​

The £500,000 (€716,000) grant has been awarded by the UK Government to develop a version of the polymer suitable for systemic administration. This hinges on finding a biodegradeable polymer that breaks down in the body without forming harmful degradation compounds.

At present, CTS' manufactures a product based on a hydrogel polymer for cervical ripening in women during childbirth. This product, sold as Cervidil in the US and Propess elsewhere, does not biodegrade, but as it is administered locally this is not a problem. After its active payload has been delivered, the hydrogel matrix can easily be retrieved.

CTS has already identified a version of the polymer that is biodegradable, and will use the new grant as part of a £1.5 million project to develop this sufficiently to allow proof-of-principle testing in the clinic, said a spokesman for the firm. Initial work suggests that the working version may be suitable for both systemic and depot administration under the skin.

The spokesman told In-Pharmatechnologist.com that CTS' strategy is to prove that the hydrogel works and then find pharmaceutical partners to share the development and clinical costs of bringing a product based on the technology to market.

Aside from the biodegradability issue, CTS' polymer has a number of other advantages over PEG-based approaches to drug delivery. For example, it offers a smooth, predictable drug release that avoids the 'spiking' that can occur with PEG-based products and theoretically could reduce side effects and improve compliance with therapy.

It also improves the stability of the drugs, which can confer added advantages in terms of a longer shelf life, said the firm.