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Pfizer

The Fight against HIV Gets Personal

With a virus that mutates as rapidly as HIV, clinicians have to work hard to know the exact nature of their enemy in each individual patient and choose their weapons appropriately. Anti-viral drugs are developed for several different stages of the HIV life cycle and are used in combination to combat the development of resistance to any single drug. These treatments have been effective, reducing the death rate by 70 percent since 1995 according to the CDC, but more needs to be done.

With FDA approval of Selzentry^® for treatment-experienced adults in 2007, Pfizer deployed the first new class of HIV drug in over a decade. Selzentry is a personalized treatment unique for its novel mode of action and for its use of a diagnostic to determine patient responsiveness.

The Food and Drug Administration, in a harbinger of likely future actions, has just approved a drug-diagnostic combination for AIDS patients who are running out of treatment options. Selzentry™, a drug developed by Pfizer Inc, will require a diagnostic test developed and conducted by Monogram Biosciences to ensure that it will work for individual patients, the hallmark of personalized medicine.

Edward Abrahams
Personalized Medicine Coalition, 2007

HIV enters healthy immune cells, known as CD4 cells, through one of two cellular gateways. To gain entry, most HIV strains use the CCR5 receptor (and are called "CCR5-tropic") but some use the CXCR4 receptor. Still other HIV strains use both. Selzentry works by blocking HIV from attaching to the CCR5 receptor, thereby preventing entry into and infection of healthy immune cells. Knowing that not all HIV strains work through the CCR5 receptor, Pfizer researchers wanted a way to determine up front which patients would benefit from the drug. Giving an ineffective treatment to patients not only slows the process of getting the right therapy to the right patient, it also carries risk of promoting viral mutation.

Pfizer collaborated with Monogram Biosciences, which was developing a diagnostic test to find out if a patient's virus was CCR5-tropic. Pfizer used the Trofile™ assay to select patients for clinical trials of Selzentry. In another first for the HIV field, the FDA-approved label requires tropism testing to identify patients infected with CCR5-tropic virus to guide treatment. Pfizer is now seeking to expand the use of Selzentry to make it a first line of defense in treatment-naïve patients who carry the CCR5-tropic strain.

Trofile is currently the only clinically validated HIV tropism assay, and Pfizer and Monogram's work has paved the way for its use in clinical trials for other CCR5-antagonists currently in development. The assay itself has since been refined to detect virus that does not act through CCR5 at levels as low as 0.3% of a viral population. But, as HIV has moved from a terminal illness to a manageable chronic disease, companion diagnostics will be increasingly required to ensure that the right medicines are used to keep the virus under control. Until a cure for HIV is found, moving beyond a trial-and-error treatment approach to an individually tailored choice among HIV anti-virals is the next stage in our evolving ability to fight this disease.