London, UK, 18 December 2009 - Ark Therapeutics Group plc (AKT: LSE) (“Ark” or “the Company”), announces that it has received notice from the European Medicines Agency (EMEA) that the European Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion for Ark’s marketing authorization application (MAA) for Cerepro®, Ark’s novel gene-based therapy for operable malignant glioma (brain cancer). The filing was based on results from the “904” phase III trial and Ark intends to provide data to support re-examination through the standard appeal procedure.
EMEA opinion
The MAA application for Cerepro® was filed in November 2008 and has undergone formal review via the centralised procedure.
The main underlying objection from the regulator which had not been resolved concerns specifically whether or not patients treated with Cerepro® might for some reason, have been left longer by surgeons prior to re-intervention than those who did not receive Cerepro®. As time to re-intervention is the main efficacy measure in the primary endpoint, the assessors determined that they could not recommend approval based on the data presented by Ark so far. The CHMP has thus adopted a negative opinion as Ark had not at that point in time provided trial evidence beyond doubt that Cerepro® has demonstrated adequate efficacy. Significantly, all issues relating to the other elements of the regulatory package, notably the key Chemistry and Manufacturing Controls (CMC), Pre-clinical and Environmental Dossiers were cleared by the assessors and were thus deemed ‘approvable’.
Cerepro® has Orphan Drug Status in both Europe and the USA and is manufactured by Ark in Finland.
Professor Seppo Ylä-Herttuala, Consultant Director of Molecular Medicine at Ark commented: “Cerepro® has produced good safety and efficacy data in a difficult to treat disease where new treatments are much needed. It has the potential to be the first gene-based medicine to be approved and, as such, is navigating uncharted waters from a regulatory perspective. It is perhaps unsurprising therefore that the approval process is taking longer than patients would hope for, but it is significant that the adenovirus platform technology has no outstanding issues and I believe it is a matter of time before the product gains approval.”
Nigel Parker, CEO at Ark, added: “We are naturally very disappointed with this opinion. We have a considerable body of evidence from the study which we believe will address the main objection with respect to re-intervention. We are planning to file for re-assessment in a matter of days and expect the appeal process to take about four months. Despite this setback, we are pleased that Ark’s underlying adenovirus platform has cleared all other barriers to a full approval. This is a major milestone both for Ark and the industry and gives us the confidence to progress development of our complete adenovirus portfolio.”
Re-intervention
Study 904 was an open label study and as with any open study where it is not ethical to administer a placebo, there is always the potential for bias. The regulator’s main objection was that the primary endpoint re-intervention decision may have contained elements of physician subjectivity which might have favoured the Cerepro® treated patients. Ark had provided, as part of the last review stage, data which showed that recurrent tumour volumes at the pre-reintervention MRI scan and the time elapsed thereafter to actual re-intervention were similar in active and control groups. The data indicated no bias on these important physical re-intervention related parameters. The precise subjectivity concern was discussed during questions in the last presentation by Ark to the regulator and as yet remains unresolved.
Ark believes it has substantial data from the main trial with which to address this issue. The trial endpoints and analyses used in Study 904 reflect the latest published recommendations from international expert working groups reviewing glioma trial design.
Whilst overall survival was consistently in Cerepro®’s favour in Study 904, with hazard ratios showing a 16%-29% benefit from Cerepro®, these data were not considered adequate as improvements were not statistically significant across all study analyses. On this basis, the regulator determined the Phase III trial has, so far, failed to prove efficacy and the range of positive analyses, including MGMT status results, may have been chance findings.
Next steps
Ark expects to close the financial year with over £20m of cash. While Ark remains confident that it has strong data to support the re-examination in early 2010, the delay which the appeal process introduces means that the Company believes that it is prudent to undertake actions now to reduce its cost base. Ark’s wound care business has continued to show growth in excess of 70% year to date and is approaching sustainable profitability. In addition to the contract already announced with Oy Lx Therapies Ltd, Ark has recently signed a further agreement to commence manufacturing process development for a second company and will continue to respond to enquiries in its specific areas of expertise.
Malignant glioma
Malignant glioma is a devastating and fatal form of brain tumour that is usually confined to the brain. The current standard therapy involves surgically removing the solid tumour mass (when possible) and initiating radiotherapy and/or chemotherapy. Even with the latest approved treatments, many patients die within one year of diagnosis, with average survival being about fourteen months. Little therapeutic progress has been made in recent years and the prognosis for malignant glioma patients is poor. A high unmet clinical need exists for new treatments that prolong life in this devastating disease. There are approximately 16,000 cases of malignant glioma in the EU which are operable.
Cerepro®
Cerepro® is an adenoviral mediated gene-based medicine (ad.HSV tk) given by multiple injections into the healthy brain tissue of patients following surgical removal of the solid tumour mass. In the following days, ganciclovir, is given intravenously. Once treated, healthy brain cells surrounding the site where the tumour was removed express the enzyme thymidine kinase. This converts the ganciclovir to a substance which specifically kills dividing cells. The healthy neurones surrounding the tumour in the brain are non-dividing and are therefore not susceptible to this substance. In this way Cerepro® harnesses healthy brain cells to help prevent a new tumour from growing.
About Ark Therapeutics Group plc
Ark Therapeutics Group plc is a specialist healthcare group (the “Group”) addressing high value areas of unmet medical need within vascular disease, wound care and cancer. These are large and growing markets, where opportunities exist for effective new products to generate significant revenues. With six marketed devices, Kerraboot®, Kerraped®, Flaminal®, Neuropad®, KerraMax® and Kerraglove®, three further lead pharmaceutical products in late stage clinical development: Cerepro®, Vitor™, and Trinam® and two in Phase I/IIa trials, EG011 and EG016 the Group is transitioning from an R&D company to a commercial, revenue generating business.
Ark’s own products are sourced from related but largely non-dependent technologies within the Group and have been selected to enable them to be taken through development within the Group’s own means and to benefit from Orphan Drug Status and/or Fast Track Designation, as appropriate. This strategy has allowed the Group to retain greater value and greater control of clinical development timelines, and to mitigate the risks of dependency on any one particular programme or development partner. Ark has secured patents or has patent applications pending for all its lead products in principal pharmaceutical markets.
Ark has its origins in businesses established in the mid-1990s by Professor John Martin and Mr Stephen Barker of University College London and Professor Seppo Ylä-Herttuala of the AI Virtanen Institute at the University of Kuopio, Finland, all of whom play leading roles in the Company’s research and development programmes.
Ark’s shares were first listed on the London Stock Exchange in March 2004 (AKT.L).
