SALT LAKE CITY, Utah, May 29, 2015 - Myriad Genetics, Inc. (NASDAQ: MYGN) today announced new clinical studies on its myChoice HRD companion diagnostic test at the 2015 American Society of Clinical Oncology annual meeting being held in Chicago, Ill.
Myriad's myChoice HRD test is the first and only companion diagnostic to measure three modes of homologous recombination deficiency (HRD) including loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions in cancer cells. The myChoice HRD score is a biomarker that indicates the inability of cancer cells to repair DNA damage and reflects a tumor's sensitivity to DNA-damaging medicines such as PARP (poly-ADP ribose polymerase) inhibitors and platinum-based therapies.
"The myChoice HRD companion diagnostic test stems from Myriad's pioneering research and is a real step forward in realizing the goal of personalized medicine for patients with ovarian, breast and pancreatic cancers and possibly other solid tumors," said Jerry Lanchbury, Ph.D., chief scientific officer, Myriad. "Anybody who has ever had cancer or treated patients with cancer will understand the enormous benefit of getting the right treatment to the right patient at the right time. There is mounting evidence that myChoice HRD can help us do that by predicting a therapeutic response to DNA-damaging agents based on patients' unique tumor biology." Below are the key myChoice HRD presentations being highlighted at #ASCO15.
myChoice HRD: Predicting Platinum Response
Poster Discussion (Poster 32): Combined Homologous Recombination Deficiency (HRD) Scores and Response to Neoadjuvant Platinum-Based Chemotherapy in Triple Negative and/or BRCA1/2 Mutation-Associated Breast Cancer.
Melinda Telli, M.D. (Stanford University School of Medicine) will present new clinical data that established a homologous recombination (HR) deficiency threshold that can identify 95 percent of patients with mutations in BRCA1/2 and other homologous recombination genes and who have a higher likelihood of responding to treatment with DNA-damaging agents. Specifically, the study validated an HRD threshold score of ?42 (on a scale of 0-100) using a training cohort of 497 breast and 561 ovarian cancer patients. A myChoice HRD test score ?42 represents a positive score or a loss of DNA repair function, while a myChoice HRD score <42 reflects a negative score or an intact DNA repair function. Using this threshold, the myChoice HRD test was then evaluated to predict response to neoadjuvant platinum-based chemotherapy in patients with TNBC or BRCA1/2 mutation-associated breast cancer. The endpoints of this analysis were residual cancer burden (RCB) and pathological complete response (pCR). The results showed that a positive myChoice HRD score and/or a BRCA1/2 mutation were statistically significantly associated with treatment response (Table 1), and importantly, the myChoice HRD test identified responders lacking a deleterious BRCA1/2 mutation. In this study, myChoice HRD predicted nearly double the number of patients who would likely respond to neoadjuvant platinum-based chemotherapy compared to BRCA1/2 mutations alone or other clinical features.
Table 1: HR Deficiency Status (N=72)| Responded to treatment | HR Deficient (% response) | Non-HR Deficient (% response) | P Value |
|---|---|---|---|
| pCR=No | 30 | 19 | |
| pCR=Yes | 21 (41.2 %) | 2 (9.5%) | 0.0050 |
(1) Includes myChoice HRD score and/or BRCA1/2 mutation status.
Podium Presentation (Abstract 1004): Prediction of Pathological Complete Response (pCR) by Homologous Recombination Deficiency (HRD) after Carboplatin-Containing Neoadjuvant Chemotherapy in Patients with TNBC: Results from GeparSixto.
Prof. Gunter Von Minckwitz (German Breast Group, Isenburg, Germany) will show data in a featured podium presentation that demonstrate the ability of the myChoice HRD test to predict pathological complete response (pCR) to platinum chemotherapy in patients with triple negative breast cancer (TNBC). A total of 193 patients with TNBC who received paciltaxel/liposomal doxrubicin or paciltaxel/liposomal doxrubicin +carboplatin in the GeparSixto trial were evaluated with the myChoice HRD companion diagnostic test using the clinically validated endpoint from the Telli study above.
Of these, 136 (70 percent) patients were myChoice HRD positive due to a high test score and/or a deleterious tumor mutation in the BRCA1/2 (tBRAC) genes, which reflect HRD. Using the original study endpoint (pCR = ypT0 ypN0), the highest response rate in the primary analysis of 63.5 percent was observed in patients who were myChoice HRD positive and were treated with carboplatin/standard-of-care (Table 2). Importantly, in a supplemental analysis, the statistically significant response rate remained in patients who were myChoice HRD positive but had no mutation in the BRCA1/2 genes (Table 3). These data indicate that myChoice HRD is a highly sensitive biomarker, regardless of the cause of HRD, and support using the myChoice HRD test to identify patients who are likely to respond to DNA-damaging agents like carboplatin.
Table 2: All Tumors| (pCR = ypT0 N0) | Paciltaxel/Liposomal Doxrubicin (PM) | PM+Carboplatin | P-Value |
|---|---|---|---|
| myChoice HRD Positive | 33.9 (n=62) | 63.5 (n=74) | <0.001 |
| myChoice HRD Negative | 20.0 (n=30) | 29.6 (n=27) | .54 |
| P-Value | 0.22 | 0.003 |
Table 3: myChoice HRD Positive
| (pCR = ypT0 N0) | Paciltaxel/Liposomal Doxrubicin (PM) | PM+Carboplatin | P-Value |
|---|---|---|---|
| Positive HRD score with no tumorBRCA1/2 mutation | 31.7 (n=41) | 63.2 (n=38) | 0.005 |
| Tumor BRCA1/2 mutation | 38.1 (n=21) | 69.7 (n=33) | 0.022 |
(2) myChoice HRD positive = homologous recombination deficiency as measured by the combination of loss of hetrozygosity, telomeric allelic imbalance and large-scale state transitions and/or tumor mutation in the BRCA1/2 genes.
(3) myChoice HRD positive = intact homologous recombination pathway.
myChoice HRD: Predicting PARP Inhibitor Response
Poster 90: Homologous Recombination Deficiency (HRD) Score Enriches for Niraparib Sensitive High Grade Ovarian Tumors.
A presentation by Keith Wilcoxen, Ph.D., (Tesaro, Inc.), will show how BRCA status and HR-deficiency were assessed in ovarian tumors using the myChoice HRD test to predict response to treatment with niraparib, an investigational PARP inhibitor currently in Phase 3 clinical studies being conducted by Tesaro. In this Phase 3 clinical study, a myChoice HRD positive score of ?42 was used to determine loss of DNA repair function, while a myChoice HRD negative score <42 reflected intact DNA repair function. A total of 106 tumors from patients with advanced ovarian cancer were evaluated for HRD and BRCA1/2 mutations.
The results showed that all BRCA deficient tumors (n=26) were myChoice HRD positive except one. Additionally, the response to niraparib monotherapy was evaluated in 20 unique tumor models across a range of myChoice HRD scores and all of the tumors that responded to niraparib were myChoice HRD positive, irrespective of BRCA deficiency status.
These data further confirm that the myChoice HRD companion diagnostic test is predictive of BRCA deficiency and support its use to help identify patients with advanced ovarian cancer who may respond to treatment with niraparib.
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About myChoice HRD™
Myriad's myChoice HRD is the first homologous recombination deficiency test that can detect when a tumor has lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. High myChoice HRD scores reflective of DNA repair deficiencies are prevalent in all breast cancer subtypes, ovarian and most other major cancers. In previously published data, Myriad showed that the myChoice HRD test predicted drug response to platinum therapy in certain patients with triple-negative breast and ovarian cancers. It is estimated that 1.8 million people in the United States and Europe who are diagnosed with cancers annually may be candidates for treatment with DNA-damaging agents.
About Myriad Genetics
Myriad Genetics is a leading molecular diagnostic company dedicated to making a difference in patients' lives through the discovery and commercialization of transformative tests to assess a person's risk of developing disease, guide treatment decisions, and assess risk of disease progression and recurrence. Myriad is focused on strategic initiatives to grow existing markets, diversify through the introduction of new products, including companion diagnostics, and expand internationally. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com. Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, myRisk Hereditary Cancer, myChoice, myPlan Lung Cancer, BRACAnalysis CDx, HRD, Vectra and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and foreign countries. MYGN-F, MYGN-G
Safe Harbor Statement
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the myChoice HRD companion diagnostic test being a real step forward in realizing the goal of personalized medicine for patients with ovarian, breast and pancreatic cancers and possibly other solid tumors; myChoice HRD predicting a therapeutic response to DNA-damaging agents based on patients' unique tumor biology; the myChoice HRD companion diagnostic test helping to identify patients with advanced ovarian cancer who may respond to treatment with niraparib; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline or will not continue to increase at historical rates; risks related to our ability to transition from our existing to new testing services, including unexpected costs and delays; risks related to decisions or changes in the governmental or private insurers' reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities; risks related to public concern over our genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; and other factors discussed under the heading "Risk Factors" contained in Item 1A of in our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2014, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.