SOUTH SAN FRANCISCO, Calif., Aug. 12 /PRNewswire-FirstCall/ -- Monogram Biosciences, Inc. today reported that four studies demonstrating the utility and clinical significance of its Trofile(TM) co-receptor tropism assay will be presented at the XVI International AIDS Conference in Toronto. The studies suggest the need for and value of phenotypic assays in evaluating co-receptor tropism. Tropism refers to the specific cellular co-receptors (either CCR5 or CXCR4) that individual strains of HIV use to gain access to host cells. Analyzing tropism plays an essential role in determining whether the use of new drugs which target the CCR5 co-receptor (CCR5 antagonists) is likely to be effective in individual HIV-infected patients.
Monogram’s Trofile assay is able to directly and accurately determine whether a patient’s virus is able to gain entry into cells via the CCR5 or CXCR4 co-receptor, or a combination of the two. The Trofile assay has been used for patient selection in Pfizer’s phase III trial of maraviroc, its investigational CCR5 antagonist, and Monogram is collaborating with Pfizer Inc. to make its co-receptor tropism assay available for patient use on a global basis in anticipation of FDA and EMEA approval.
“Drug resistance continues to be a major problem in HIV management, and patients are in need of new classes of drugs, including CCR5 antagonists,” said Monogram CEO Bill Young. “Despite advances in treatment options for HIV-infected patients, we know that not every drug candidate is appropriate for every patient. Our assays help screen patients to identify those most likely to respond to these new classes of drugs based on the tropism of the infecting virus.”
The first study (Abstract #THPE0045), confirms that the Trofile assay can accurately characterize the tropism of a panel of diverse HIV strains. Researchers at Monogram used the assay to evaluate the co-receptor tropism of a panel of 46 well-characterized strains of HIV-1 that included multiple subtypes (CCR5, CXCR4, or dual/mixed tropism (DM)). The assay accurately measured the tropism of all 46 strains. The assay also was accurate when tested against three clonal viruses (CCR5, CXCR4 and DM). When CCR5 and CXCR4 clones were mixed together, the assay was able to detect minor variants down to 10 percent in all samples tested, and to 5 percent in 83 percent of samples tested. To date, 94 percent of more than 8,000 samples received for ongoing clinical trials of co-receptor antagonists in North America and Europe have been successfully tested. Together, the data show that Monogram’s Trofile assay is an accurate, precise, sensitive, reproducible and robust assay for the measurement of tropism and support its use as the standard assay for patient screening and monitoring in the development of co-receptor antagonists.
The second study, also presented by Monogram scientists (Abstract #THPE0046), compared the abilities of V3 sequencing and Monogram’s Trofile assay to accurately characterize tropism. V3 sequencing examines the genetic sequence of only the V3 region of the envelope gene of HIV taken from a patient and uses algorithms to predict co-receptor tropism. The Trofile assay uses the entire envelope gene taken from the patient’s virus to measure viral tropism directly. The study used patient-derived virus sequences representing multiple subtypes of HIV-1, and found that sensitivity for detection of viruses using the CXCR4 co-receptor varied widely depending on viral sub-type and on the interpretation system used. In comparison to phenotypic analysis with Trofile, which accurately and directly measures co-receptor usage, genotypic measures, on average, were only approximately 65% accurate, and in many cases were even less accurate. These results demonstrate that genotypic approaches are inferior for assessing tropism when compared with Trofile.
“These data confirm that the Trofile assay is more sensitive and precise in determining co-receptor tropism,” said Chris Petropoulos, Chief Scientific Officer. “The region of the virus involved in cellular entry has a particularly heterogeneous genetic sequence, which renders genotypic methods significantly less effective.”
In a study (Abstract #THLB0215) presented by scientists from Pfizer, Inc., the negative predictive value of Monogram’s Trofile co-receptor tropism assay was assessed in an ongoing Phase III trial of Pfizer’s investigational CCR5 antagonist, maraviroc (Study 1029). Results show that patients identified by the assay as having virus using both the CXCR4 and CCR5 receptors (dual/mixed tropic) did not respond to the investigational (CCR5) therapy. These data suggest that screening patients with the Trofile assay will allow physicians to avoid treating patients with expensive drug therapy who are unlikely to respond to that therapy.
A separate study (Abstract #THLB0217) presented by investigators from the AIDS Clinical Trial Group 5211 study team and Schering Plough demonstrated the positive predictive value of the assay in patients participating in a Phase IIb trial of Schering-Plough’s investigational CCR5 antagonist vicriviroc. In this study, patients identified by the assay as having virus utilizing only the CCR5 co-receptor demonstrated clinical responses to the investigational therapy.
“These data suggest that the Trofile co-receptor tropism assay is an effective method of identifying appropriate patients for treatment with CCR5 antagonists,” said Petropoulos. “By virtue of its high positive and negative predictive values, the Trofile assay is highly capable of insuring that individuals receive treatments that are most likely to provide them with clinical benefit.”
About Monogram Biosciences, Inc.
Monogram is advancing individualized medicine by discovering, developing and marketing innovative products to guide and improve treatment of serious infectious diseases and cancer. The Company’s products are designed to help doctors optimize treatment regimens for their patients that lead to better outcomes and reduced costs. The Company’s technology is also being used by numerous biopharmaceutical companies to develop new and improved antiviral therapeutics and vaccines as well as targeted cancer therapeutics. More information about the Company and its technology can be found on its web site at www.monogrambio.com .
Forward Looking Statements
Certain statements in this press release and attached supplemental information are forward-looking. These forward-looking statements include references to the potential for an HIV drug that requires a molecular diagnostic for patient selection, These forward-looking statements are subject to risks and uncertainties and other factors, which may cause actual results to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that regulatory authorities may not require a molecular diagnostic for patient selection for an HIV drug, risks related to the implementation of the collaboration with Pfizer; risks and uncertainties relating to the performance of our products; the growth in revenues; the size, timing and success or failure of any clinical trials for CCR5 inhibitors or entry inhibitors; the use of our Co-Receptor Tropism Assay for patient use in the event of approval of any CCR5 inhibitors; our ability to successfully conduct clinical studies and the results obtained from those studies; whether larger confirmatory clinical studies will confirm the results of initial studies; our ability to establish reliable, high-volume operations at commercially reasonable costs; expected reliance on a few customers for the majority of our revenues; the annual renewal of certain customer agreements; actual market acceptance of our products and adoption of our technological approach and products by pharmaceutical and biotechnology companies; our estimate of the size of our markets; our estimates of the levels of demand for our products; the impact of competition; the timing and ultimate size of pharmaceutical company clinical trials; whether payors will authorize reimbursement for our products and services; whether the FDA or any other agency will decide to further regulate our products or services; whether we will encounter problems or delays in automating our processes; the ultimate validity and enforceability of our patent applications and patents; the possible infringement of the intellectual property of others; whether licenses to third party technology will be available; whether we are able to build brand loyalty and expand revenues; and whether we will be able to raise sufficient capital in the future, if required. For a discussion of other factors that may cause our actual events to differ from those projected, please refer to our most recent annual report on Form 10-K and quarterly reports on Form 10-Q, as well as other subsequent filings with the Securities and Exchange Commission. We do not undertake, and specifically disclaim any obligation, to revise any forward-looking statements to reflect the occurrence of anticipated or unanticipated events or circumstances after the date of such statements.
Trofile is a trademark of Monogram Biosciences, Inc. Contacts: Alfred G. Merriweather Jeremiah Hall Chief Financial Officer Feinstein Kean Healthcare Tel: 650 624-4576 Tel: 415 677-2700 amerriweather@monogrambio.comjeremiah.hall@fkhealth.com
Monogram Biosciences, Inc.
CONTACT: Alfred G. Merriweather, Chief Financial Officer of MonogramBiosciences, Inc., +1-650-624-4576, amerriweather@monogrambio.com; orJeremiah Hall of Feinstein Kean Healthcare, +1-415-677-2700,jeremiah.hall@fkhealth.com
Web site: http://www.monogrambio.com/
