Biomarker data on Introgen's p53 tumor suppressor Advexin shows 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 respond better to treatment.

Patients with the favorable p53 biomarker profile had a statistically significant increase in response and survival, the Austin, Texas, company said. Introgen released the biomarker data April 13 during the American Association for Cancer Research annual meeting in San Diego.

"We have identified these biomarkers that really have the ability to identify patients that clearly will not have a beneficial response to Advexin and those where the efficacy is seen," Senior VP-Medical and Scientific Affairs Robert Sobol said in an interview with "The Pink Sheet" DAILY. "That provides us with that opportunity of that precision that FDA and other regulatory agencies are seeking."

With the confirmatory biomarker data, Introgen plans to seek approval of Advexin in recurrent head and neck cancer patients with tumors expressing the wild type p53 gene, which would include a majority of patients. Those with tumors expressing a mutated p53 gene represent about one-quarter to one-third of patients with recurrent head and neck cancer, Sobol said. However, one unanticipated result of the data is that the comparator arm, methotrexate, benefited patients with the mutated p53 gene, he noted.

The filing for Advexin is on target for the second quarter of 2008, the exec said. Introgen initially had anticipated completing the rolling submission for the adenovirus-based therapy in 2007, but delayed the filing until 2008 to include data strengthening its p53 biomarker analysis (¹ Also see "Introgen Anticipates Completion Of Advexin Rolling BLA Submission In 2007" - Pink Sheet, 29 December, 2006.).

Abnormal p53 tumor suppressor function is associated with cancer initiation, progression and treatment resistance.

The data were generated from a Phase III study, 301A and B, evaluating tumor response and survival in patients with recurrent head and neck cancer. Full results of the trial, including survival data, will be released later this year and serve as the basis for regulatory submissions in the U.S. and Europe.

Of patients treated with Advexin monotherapy, 86 percent of those with wild type p53 gene demonstrated tumor growth control versus 53 percent of those with the mutated gene, according to a poster of the data. The results were opposite of the results seen in patients treated with methotrexate, in which 55 percent of those with the wild type gene had tumor growth control versus 87 percent of those with the mutated gene.

An analysis from head and neck cancer patients in Phase I, II and III trials showed that 79 percent of those with the favorable biomarker profile for Advexin had a tumor response following treatment with the drug, compared to 25 percent of patients with the unfavorable p53 biomarkers for Advexin.

Introgen is seeking a partner for Advexin and discussions are ongoing, the firm said.

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

Introgen Advexin Data Strengthens Biomarker Case In Head And Neck Cancer Patients

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