Access to DACH analogue

Access Pharmaceuticals has provided an update on the status of its AP5346 polymer platinate product and progress in the development of the next generation of polymer therapeutics for the treatment of cancer.

The use of platinum compounds for the treatment of cancer continues to expand with worldwide sales in 2003 exceeding $2bn. Oxaliplatin, the first marketed Dichloro-1,2-diaminocyclohexane (DACH):platinum(II) (DACH-platinum) compound, which is approved for use in combination with 5-flourouracil (5-FU) and leucovorin as first line therapy for colorectal cancer, recorded sales in excess of $1bn in 2003.

AP5346, Access' tumour-targeted analogue of DACH-platinum offers the potential to improve the anti-tumour activity and the toxicity profile of platinum compounds. The AP5346 program is designed to selectively deliver DACH platinum to tumours by capitalising on the differences in the permeability of blood vessels at tumour sites versus normal tissue.

Toxicity

Recently published clinical data by Gamelin, et. al. in the Journal of Clinical Cancer Research and previously conducted in vitro work by the same group implicates oxalic acid, an essential component of oxaliplatin, as the major contributor to the neurotoxicity of the compound. AP5346 does not contain oxalic acid, and, to date, there has been no evidence of neurotoxicity in our Phase I clinical study, an observation which is supported by preclinical data for AP5346.

Investigational New Drug Application (IND)

Access has conducted a pre-IND meeting with the FDA and now plans to file an IND this quarter. The IND will request approval to commence a clinical study to evaluate AP5346 in combination with 5-FU and Leucovorin to determine the clinical dosing regimen. On the successful completion of this study, a Phase II study evaluating AP5346 in combination with 5-FU and Leucovorin in colorectal cancer is planned to be conducted.

Additional preclinical results

AP5346 has now been tested in 12 preclinical animal models, and data from these studies have clearly established the superiority of AP5346 compared to oxaliplatin in these models. Most recently AP5346 was evaluated in combination with 5-FU and Leucovorin in an animal colorectal cancer model and compared with the standard combination of oxaliplatin, 5-FU and Leucovorin and with AP5346 alone. The combination with AP5346 showed significantly superior tumour growth inhibition than either AP5346 alone or the oxaliplatin combination.

AP5346 Clinical Development Plan

In addition to the US IND study described above, Access plans to commence a Phase II clinical study during the third quarter in Europe to evaluate AP5346 in recurrent advanced ovarian cancer. This will be a single agent study designed to assess tumour response and the toxicity profile when administered over an extended period. Additionally, Access plans to conduct a study in head and neck cancer patients to evaluate tumour response and the ability to deliver more platinum to the tumour DNA compared with oxaliplatin. This study is designed to confirm the previously reported animal data, which showed that in excess of 10 times more platinum tumour DNA complexes were formed by AP5346 compared to oxaliplatin.

Phase I Clinical Data

'We are very excited at the prospects for our polymer platinate program,' Access Pharmaceuticals president and ceo Kerry Gray stated. 'Given the extensive preclinical data supporting AP5346 and the potential to improve the neurotoxicity profile, which can be a chronic problem, AP5346 could represent a significant improvement over the currently available treatment. If we continue to achieve the positive results accomplished to date, the value of this asset will be greatly enhanced, as our patents covering this development do not expire until 2020.'

Next generation polymer therapeutics

As part of our ongoing program to develop enhanced polymer therapeutics, recently conducted pre-clinical studies have shown that further improvements in tumour growth inhibition can be achieved through polymer design. The studies, conducted in a colorectal cancer animal model, showed a significant tumour growth inhibition and survival benefit when the polymer design parameters are optimised. Utilising these data, Access plans to expand its cancer development program with the objective of advancing two additional products into clinical development within 18 months.

Gray continued: 'The work conducted to date and the study results achieved clearly indicate the potential to further improve the benefits of the polymer therapeutics approach in cancer treatment. The potential to increase delivery of drug to tumour and improve the toxicity profile of chemotherapeutics represents a significant market opportunity if these benefits are attained.'