Introgen plans to submit regulatory filings for the p53 tumor suppressor Advexin to FDA and the European Medicines Agency by the end of June, including data from a Phase III trial showing the treatment more than doubled survival in head and neck cancer patients with p53 favorable profiles.

Advexin, the most advanced gene therapy in development in the U.S., has been on the brink of regulatory filing for years, but the timeline has been pushed back.

The Austin, Texas, company earlier this year released biomarker data showing that head and neck cancer patients with tumors expressing a high level of the wild type p53 gene and a low level of the mutated p53 gene responded better to treatment with Advexin compared with methotrexate (¹ Also see "Introgen Advexin Data Strengthens Biomarker Case In Head And Neck Cancer Patients" - Pink Sheet, 14 April, 2008.).

The firm plans to present survival data from the open-label study comparing Advexin treatment versus methotrexate May 29 at the American Society of Gene Therapy Meeting in Boston. This data could be critical to the drug's approval success.

The study enrolled 123 patients with recurrent squamous cell carcinoma of the head and neck whose cancers were refractory to platinum or taxane chemotherapy. Patients were randomized to receive Advexin or methotrexate as monotherapy.

Advexin significantly increased survival in patients with p53 favorable biomarker profiles compared to patients with p53 unfavorable profiles (7.2 months versus 2.7 months). Patients treated with methotrexate who had favorable p53 profiles had median survival of 4.3 months. However, those with p53 biomarker profiles unfavorable to Advexin treated with methotrexate had median survival of 5.9 months.

Favorable p53 biomarkers also were associated with a significant increase in tumor responses to Advexin. In pivotal Phase II and Phase III trials, tumor response was 78.4 percent in patients with p53 favorable profiles compared to 26.8 percent in patients with p53 unfavorable profiles. Reverse associations were likewise seen in methotrexate-treated patients, with a higher proportion of responders observed in those with p53 unfavorable profiles.

No significant difference was seen in survival between Advexin and methotrexate-treated patients in the intent to treat population, including both p53 favorable and unfavorable patients in both study arms (6.1 months versus 4.4 months).

Introgen plans to seek approval of Advexin in recurrent head and neck cancer patients with tumors expressing the wild type p53 gene, which represents a majority of patients. The company is seeking a partner for the drug.

Big pharma has yet to move full throttle into gene therapy, after several high-profile setbacks years ago. More recently, firms have revved up activity in the space.

Last year, Genzyme partnered with Ceregene on a Phase II gene therapy for Parkinson's disease (² Also see "Genzyme Licenses Gene Therapy Candidate For Parkinson’s Disease" - Pink Sheet, 21 June, 2007.). Sanofi-Aventis also acquired a global license to develop and commercialize Oxford BioMedica's gene-based renal cancer therapy TroVax , now in Phase III (³ Also see "Sanofi Gains Therapeutic Cancer Vaccine TroVax In Deal With Oxford BioMedica" - Pink Sheet, 28 March, 2007.).

-Jessica Merrill (j.merrill@elsevier.com)

Introgen’s Advexin Doubles Survival In Some Head &amp; Neck Cancer Patients

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Introgen’s Advexin Doubles Survival In Some Head & Neck Cancer Patients