Monogram Biosciences' partner Pfizer will distribute globally Monogram's CCR5 co-receptor tropism assay, which may allow physicians to determine which HIV-positive patients will respond to Pfizer's experimental HIV compound Maraviroc.
Pfizer has invested $25 million in the company and has expanded an existing collaboration with Monogram based around its HIV co-receptor tropism assay.
If approved, Maraviroc, which is currently in phase III trials, will become the first CCR5 antagonist to be approved by the US Food and Drug Administration, and Monogram's phenotypic CCR5 assay has the opportunity to become the first such test on the market. It could also prove to be useful in predicting patient response to other drugs of the same class.
Monogram has been providing the test as a CLIA-lab service to Pfizer for use in its Maraviroc trials since 2002, when it was known as ViroLogic, a Pfizer spokesperson told Pharmacogenomics Reporter this week. Pfizer will market the test in this format for its prescribers, and Monogram has no plans to apply for FDA clearance, said Merriweather.
"Given that our test was used to select patients for the trial, it's reasonably likely that the test will have some association with the use of the drug in the commercial world after approval," said Alf Merriweather, Monogram CFO, this week in an interview. "We're ready to begin commercializing [the assay] in the United States as soon as the drug is approved."
"Given that our test was used to select patients for the trial, it's reasonably likely that the test will have some association with the use of the drug in the commercial world after approval."
Pfizer expects to file a new drug application for Maraviroc by the end of the year, the company said in a statement last week. In that statement, Pfizer said the FDA's data safety monitoring board had recommended proceeding with phase III development in untreated patients and in patients previously treated with anti-retroviral drugs.
Pfizer plans to distribute Monogram's CLIA-based CCR5 tropism assay services worldwide in preparation for FDA approval of Maraviroc, which the company hopes to launch globally.
Currently Monogram sells its products only in the United States, and it will control CCR5 marketing in this country. But so far, it is not quite clear what, if any, mention of the test will be added to Maraviroc's label. "We'll certainly take advantage of whatever labeling will come out of the FDA trial," said Merriweather.
Outside the United States, Pfizer will control the test's marketing, sales, reimbursement, and regulatory issues, he said.
In order to help Monogram support testing worldwide, Pfizer has invested $25 million in the company through a four-year convertible note with a 3-percent coupon, according to a Pfizer spokesperson.
The UNAIDS 2004 Report on the Global AIDS Epidemic estimates that in 2003, the most current year for which data are available, about 5 million people became infected with HIV, and about 38 million were living with the virus.
About 80 to 85 percent of newly diagnosed HIV patients may be eligible for Maraviroc, and about half the HIV patients who have previously been treated with anti-retroviral drugs may be suited to Maraviroc treatment, Pfizer said.
Maraviroc and other CCR5 antagonists block the cell-surface receptor CCR5 from HIV, which binds the protein to gain entry into white blood cells. Monogram's test identifies CCR5-dominant HIV strains by comparing virus replication in CCR5-expressing target cells and CXCR4-expressing cells. CXCR4 is the other co-receptor used by HIV. Monogram scientists insert the virus' genes isolated from patient samples by PCR and a reporter gene into virus particles capable of one round of reproduction. They then infect target cells in vitro and detect the reporter signal in separate populations of CCR5- or CXCR4-expressing cells.
The CCR5 test is intended to identify responders before prescribing, in contrast to Monogram's phenotypic drug-resistance tests, which work in a similar fashion, but are intended to determine which drugs a particular strain has become resistant to.
Another CCR5 antagonist under development is Schering-Plough's vicriviroc, for which two phase 3 clinical trials are planned but have not begun recruiting. Human Genome Sciences is currently recruiting patients for a phase 1 clinical trial for its anti-CCR5 antibody, CCR5mAb004, and GlaxoSmithKline last year halted trials of its compound GW873140 due to concerns about liver toxicity.
Chris Womack ([email protected])