Ark Therapeutics Group plc announced that the preliminary analysis of Study 904, a phase-III study of Cerepro, its novel gene-based therapy being developed as an Orphan Drug for the treatment of operable primary malignant glioma, demonstrates that the trial has met its primary endpoint. Cerepro treatment resulted in significant improvements in median survival on the primary endpoint compared with various control groups. In the secondary endpoints, with 45 per cent of patients still alive, benefits have yet to be established.
Study 904 was a multi-centre, standard care controlled, pivotal trial in 236 patients designed, following advice from the EMEA, to confirm the safety and efficacy of Cerepro in patients with operable high grade glioma (brain cancer) against current standard care treatment options. Patients were randomized to either standard care plus Cerepro or standard care alone. Standard care was surgery and radiotherapy or surgery and radiotherapy followed by temozolomide, depending on the investigating centres' standard practice and patient suitability, giving four treatment groups. This allowed comparison of the efficacy of Cerepro and temozolomide in the same trial without denying patients what physicians considered the appropriate established standard care. The primary endpoint was survival, defined as time to death or re-intervention. At randomisation, the treatment groups were well matched in terms of demographics and the standard prognostic features (age, Karnofsky Score etc).
The overall combined controls primary endpoint analysis in the Intention to Treat (ITT) population (n=236) compared Cerepro with and without temozolomide against controls with and without temozolomide. It showed a 42-day improvement in median survival (310 days vs 268 days) and the improvement over standard care reached significance (p<0.032). The analysis was performed approximately 14 months after completion of recruitment.
On the primary endpoint, the group given Cerepro and temozolomide showed an improvement of 68 per cent in median survival time compared with standard care surgery and radiotherapy controls (350 days vs 208 days). Against the same controls, treatment with Cerepro alone showed an improved median survival trend approaching 50 per cent, similar to those given treatment with temozolomide alone after surgery and radiotherapy (300 days and 307 days respectively vs 208 days with standard care). Improvements in the combined Cerepro and temozolomide treatment group (n=58) and temozolomide alone group (n=76) were significant (p<0.05).
On the secondary endpoints, which include MRI-based progression, all-cause mortality, safety and quality of life, the effects of Cerepro(R) treatment have yet to be established with around 45 per cent of patients still alive. Data from a further time point analysis are needed to fully elucidate this.
Commenting on the results Dr David Eckland, R&D Director at Ark, said, "We are very gratified that Cerepro has demonstrated efficacy in this multi-centre phase-3 gene therapy study. This is in keeping with our experience and expectation of the product and we now have further evidence to show Cerepro(R) has an anti-cancer effect. Our next steps are to complete the full analysis and meet with our EMEA rapporteur to determine the way forward."
Dr Nigel Parker, CEO at Ark, added, "This is the first gene therapy product to successfully reach its primary endpoint in a major phase-3 trial. With a number of patients in the trial still to report an event, there is a substantial amount of further information to come and we will update the analysis after the turn of the year in parallel with our regulatory activities. Malignant glioma is one of the most aggressive of all human diseases and to have seen a positive effect for Cerepro(R) in this disease area is very encouraging. Ark's adenoviral delivery technology has the potential to deliver a new era of gene-based therapies for acute and chronic human disease."