By Turna Ray

Based on promising Phase II results, Generex Biotechnology is planning to meet with the US Food and Drug Administration about its investigational cancer immunotherapy for breast patients who have tumors that express low to intermediate levels of the HER2 protein, the company said this week.

Generex's HER-2/neu peptide vaccine, called AE37, is being developed as an adjuvant therapy for the 50 percent of breast cancer patients who express low to intermediate levels of HER2, and as a result, don't have HER2 expression levels high enough to be eligible for Roche/Genentech's Herceptin, according to the company.

However, although the AE37 immunotherapeutic is for a molecularly defined patient population, Generex is not currently planning to develop the drug with a new companion diagnostic to gauge HER2 expression in the intent-to-treat patient population.

"At the moment we are not working to set up a separate diagnostic test" for AE37, Eric von Hofe, CEO of Generex subsidiary Antigen Express, told PGx Reporter. AE37 is the first product Generex is developing using Antigen Express's Ii-Key Hybrid technology platform.

"There is currently the Dako HercepTest that can be used for scoring tumor tissue HER2 1+, 2+ or 3+; with low to intermediate expressing tissue being 1+ or 2+," Von Hofe said. "There are other tests, as well, that are available that claim to be more quantitative."

Patients who end up receiving AE37 will likely be those who were initially being considered for Herceptin treatment and, as such, were already tested with one of several FDA-cleared HER2 tests and found to have low to intermediate HER2 expression. This may be one reason why Generex expects it will not have to develop a companion test for its product.

The FDA has indicated that when a drug requires the aid of a molecular diagnostic to determine which patients should receive it, the test, in most cases, must be approved by the agency. "An IVD companion diagnostic device is an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product," the FDA states in its draft companion diagnostics guidance, released last year.

The FDA-approved labeling for HercepTest notes that it is indicated "as an aid in the assessment of patients for whom Herceptin treatment is being considered." Given the rationale for how a breast cancer patient might become eligible to receive AE37, it is unclear whether the agency will require a separate FDA-cleared companion diagnostic to market the drug for a subset of the HER2 population.

Meanwhile, Dako and other firms marketing FDA-cleared HER2 tests that are supporting an additional indication for Herceptin or that are intended to be used with a new HER2-targeted therapy have had to seek approval for their tests in these new settings (PGx Reporter 6/2/2010; 2/8/2012).

See more here:
Generex to Meet with FDA about AE37 HER2 Peptide Vaccine; Companion Dx Path Still Unclear