OctoPlus drug delivery tech clears Phase I trial
change in 2004 as it completes its transformation from a
formulation services company to one firmly planted in drug
development.
Yesterday, the company presented its first ever clinical data - a Phase I trial of its controlled release formulation of human growth hormone (hGH) - at SMi's third annual Controlled Release Conference in London, UK.
And Luc Sterkman, OctoPlus' director of medical affairs, told In-Pharmatechnologist.com that the company expects to have three more products in the clinic by the end of the year.
The clinical trial assessed an hGH formulation based on OctoPlus' OctoDEX microspheres. These are based on modified dextran chains - already widely used in medicine in plasma extending products - that can be used to physically trap proteins in a matrix. After injection under the skin, the matrix slowly breaks down, and the protein is gradually released.
The preliminary results, presented at the meeting by Dr Leo de Leede, OctoPlus' managing director, showed that the OctoDEX formulation was able to deliver therapeutic levels of hGH over a period of nearly two weeks from a single injection.
The study was carried out in 18 male elderly volunteers who had low levels of hGH. They received a fairly low dose of hGH (0.2mg/kg) and functional activity of the protein was confirmed during the period of release by increasing levels of two well-established biomarkers for hGH activity (insulin-like growth factor-1 and IGF-binding protein-3). Sustainable, effective levels of hGH were observed for 12 days in the trial.
Controlled release formulations reduce injection frequency and increase patient comfort and compliance. They can also improve safety and efficacy of a drug by avoiding peak concentrations and achieving prolonged high concentrations in target organs and tissues.
Sterkman said that one of the attractions of this dextran technology is that, unlike PEGylation (the most widely used method of extending the plasma half life of protein drugs), there is no need to chemically modify the protein itself. This means that there should be no need to conduct expensive, large-scale clinical trials of existing protein products developed in the OctoDEX matrix.
There is a precedent for this view. Genentech's depot formulation of the growth hormone product Nutropin (somatropin) was approved after a single Phase I trial in the elderly and a Phase II evaluation in GH-deficient children, with just 151 patients in the entire clinical dossier.
"We hope this will be the case for our dextran technology," said Sterkman, although he cautioned that requirements may have gone up since Nutropin Depot was approved, because of a side effect issue that emerged in 2001 with an erythropoietin product (Johnson & Johnson's Eprex) after a slight modification to the manufacturing process.
In addition, PEGylation cannot be used with some proteins, including hGH, because of chemical incompatibilities between the protein and polymer. But while OctoDEX represents an alternative to PEGylation, there could be additional benefits to combining the two technologies, noted Sterkman.
For example, hiking the loading dose and tightening the dextran matrix might improve the duration of release of an OctoDEX-formulated protein to around three weeks. But load a PEGylated protein into the matrix and you could have a system that would deliver the protein over a month or more, further reducing the number of injections needed by patients.
OctoPlus' strategy is to develop its hGH product through a Phase II trial and then seek a commercial partner for the product, said Sterkman. This will be the basic business model for the company, although some projects will be licensed out earlier to bring in some near-term cash and spread risk.
Next month, the company will start clinical trials of another drug - called LPS-binding peptide - at Leiden University in the Netherlands. The Phase I/II study will enroll patients with chronic otitis media, a condition also known as glue ear that can cause hearing problems in children.
Also in the pipeline are a controlled-release formulation of interferon alpha, using a biodegradeable polymer-based technology developed by Chienna (a drug delivery specialist acquired from Isotis in May 2003), and a formulation of tumour necrosis factor-alpha developed alongside Cytimmune Sciences of the US.
Taking four new projects into the clinic is no small undertaking for a company of OctoPlus' size, and while the privately held firm has a revenue stream from a formulation services business, it is looking to carry out a private placement in the summer to help fund the effort.
