Monogram may become the dominant player in HIV-resistance testing with its PhenoSense GT assay.
The PhenoSense GT assay, which combines Monogram’s PhenoSense and GeneSeq technologies, is being used to optimize the background therapy for several key investigational HIV drugs, including Pfizer’s maraviroc and a pair of novel integrase inhibitors made by Merck and Gilead.
The PhenoSense tests a patient’s virus to see if it can replicate in the presence of a drug, while GeneSeq looks for mutations associated with resistance.
Chris Petropoulos, Monogram’s chief scientific officer, told Pharmacogenomics Reporter this week that the PhenoSense GT assay can help optimize the background therapy for a new HIV drug by picking a cocktail of complementary HIV drugs that will provide the most potent antiviral activity.
If physicians put patients on new HIV drugs without optimizing the background therapy, “you often put patients on drugs in which the only drug they are susceptible to is the new one, and then it quickly fails,” Petropoulos said. “That doesn’t make the drug look very good. So, it’s important these days for everyone to get tested and for the doctors to select an optimized background that can then be used in combination with the new drug.”
Recent data released at this year’s Conference on Retroviruses and Opportunistic Infections “demonstrate[d] the clinical benefit of selecting antiretroviral treatment regimens using the PhenoSense GT assay,” Monogram said in a statement.
Data from studies demonstrated that patients who only receive an optimized background regimen without an investigational drug candidate experienced a 10-fold reduction in viral replication. Almost half of treatment-experienced patients who initiated a new PhenoSense GT-selected regimen fully suppressed viral activity despite prior treatment failures, studies showed.
Enabling Integrase Inhibitors
Merck’s integrase inhibitor raltegravir may potentially be the first drug in this new class of anti-retroviral drugs. These types of drugs prevent the viral enzyme integrase from allowing HIV DNA to enter into the human genome, and in this way block HIV replications.
“Because integrase inhibitors are a brand new class there is no reason to believe that anyone would have resistance to that class yet,” said Petropoulos, whose company’s PhenoSense GT is currently in a Phase III trial with raltegravir.
Therefore, Monogram did not prospectively look for integrase resistance. “Going forward, what we will do as patients begin to [use] the integrase inhibitors, we’ll characterize both genotypically and phenotypically the resistance patterns we see.”
Eventually, Monogram’s assays will be used to test cross-resistance between raltegravir and Gilead’s integrase inhibitor elvitegravir, in which the PhenoSense GT is taking part in a Phase II trial.
However, if one is developing a new drug in a known class of HIV drugs, such as Tibotec’s Prezista, PhenoSense GT can be used to test patients’ susceptibility to the drug before prescribing it to them.
At CROI, Monogram and Tibotec reported lower and upper cutoffs for Prezista activity. The PhenoSense GT assay places HIV susceptibility to drugs in a range: below the lower cutoff means full antiretroviral activity; between the lower and upper cutoffs connotes partial activity; and above the upper cutoff signals no activity.
Monogram’s Market Penetration
With its PhenoSense line of tests, Monogram is establishing a solid foothold in the HIV optimized-background therapy market. The PhenoSense and PhenoSense GT assays are the only HIV drug-resistance tests that correlate patient response to drug susceptibility.
“It’s important these days for everyone to get tested and for the doctors to select an optimized background that can then be used in combination with the new drug.”
The advantage of PhenoSense GT is that by combining two technologies – the PhenoSense and GeneSeq – physicians get both genotype and phenotype data and gain a more complete picture of a patient’s resistance to certain treatments.
“The phenotype has much more granularity in that it’s not a binary call, it’s not resistance susceptible,” Petropoulos said. “You can actually get intermediate values, and the doctors can actually assess whether there is partial activity of a drug or if there is a complete loss of activity.”
Meantime, Monogram’s Trofile assay was used in the development program for Pfizer’s maraviroc. The HIV tropism drug is currently undergoing an accelerated review at the US Food and Drug Administration. The companies recently entered into a non-exclusive agreement to make the assay available to patients worldwide [see PGx Reporter 12-06-06].
In a release announcing its 2006 revenues, Monogram said that the use of the Trofile assay “caused a substantial increase in [the company’s] revenues in the second half of 2005 and the first half of 2006.”
The test is currently being studied in a Phase III trial, and while these results “are not yet known, we believe that because our tests were used for patient selection in the trials, it is likely that our tests may be used for patient selection after regulatory approval of maraviroc. This could result in an increase in our revenues after such approval,” Monogram said in a statement.
The company reported revenues of $48 million for the year ended Dec. 31, 2006, compared to $48.3 million for 2005. Revenue from Monogram’s HIV testing products increased to $45.2 million in 2006 from $43.5 million the previous year.
Petropoulos said that Monogram will see payments from Merck once its investigational agent enters the market. Financial details of the Monogram/Merck agreement are not known.