A silicon-based drug delivery system, developed by Australian nanotechnology company pSivida, has passed an important proof-of-concept hurdle in a clinical trial involving patients with inoperable liver cancer.
pSivida is developing a novel approach to treating inoperable liver cancer using bracytherapy, which involves the implantation of a drug that delivers short-range radiotherapy to a tumour. The new product, called BrachySil, uses the firm's BioSilicon technology to deliver radioactive phosphorous (32-P) to the tumour and subject it to beta radiation, killing off the cancer cells.
pSivida reported encouraging interim results from the Phase IIa trial in November 2004, but has just revealed new data from a second cohort of patients that underscore the efficacy of the approach.
Results from this second group of four patients, 12 weeks after their BrachySil treatment, revealed an average tumour regression by volume of 80 per cent, determined by CT scanning. These data reinforce the results from the first four patients, which found up to 60 regression of tumours.
Moreover, in some smaller tumours 100 per cent regression was observed, a level of performance not seen with other therapies delivered into the tumour itself, even though the dose of radiation used in the current study was low. The study also demonstrated that there were no product-related adverse effects. Patients will continue to be monitored for six months post treatment.
Another key characteristic of BrachySil is that the radioactive phosphorous is immobilised in the silicon, reducing the risk of soluble radioactive material affecting healthy hepatic tissue, or entering the circulation and causing systemic toxicity. This is known to occur with other brachytherapy approaches, which tend to involve injection of material into the artery supplying the liver, rather than the tumour itself.
Monitoring of patients in this study provided evidence that the radiation from the treatment was confined to the site of injection, said the firm.
Other treatments for primary liver cancer include a variety of embolisation and radio frequency ablation techniques, but pSivida believes that BrachySil could offer the interventional radiologist a more versatile and safer product for the treatment of these tumours. The procedure is undertaken without surgery under local anaesthetic and patients can be discharged the following day.
pSivida currently plans to pursue a 'device-based' regulatory approval route for BrachySil, which could result in a much shorter development and registration timeframe than that commonly associated with a drug-based approval.
Following the completion of analysis of the final Phase IIa trial results, pSivida expects to begin a dose profiling study during 2005. This will be followed by multicentre registration trials during 2005 involving patients in Asia, Europe and the US.
Meanwhile, pSivida plans to expand the use of BrachySil as a treatment for a wider range of solid tumour indications, helped by the fact that the material can be delivered down a very fine gauge needle. A Phase IIa clinical trial is scheduled to commence for a second cancer indication within the next 12 months.
The brachytherapy market is currently worth over $600 million (€460m) a year and is expected to exceed $1 billion within the next few years, according to data supplied by Bio-Tech Systems.
Meanwhile, a UK pSivida subsidiary, pSiMedica, is developing the BioSilicon platform for drug delivery applications, a much larger market opportunity at around $20bn, and recently announced that it was already in discussions with a top five pharmaceutical company to this end.