Metastatic Breast Cancer Study Reinforces Biomarker Findings From Previously Reported MM-121 Study in Ovarian Cancer Neoadjuvant Breast Cancer Study Shows Favorable Comparison in pCR Rate Between Arms CAMBRIDGE, Mass., Nov. 26, 2013 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) today announced the results of two Phase 2 studies evaluating MM-121 in the treatment of women with ER/PR+, HER2 negative breast cancer. One study was conducted in metastatic breast cancer (mBC) in combination with exemestane. The second was conducted in the neoadjuvant setting in combination with paclitaxel followed by doxorubicin and cyclophosphamide. MM-121 is a monoclonal antibody designed to target the ErbB3 (HER3) receptor and to interfere with growth factor-mediated resistance to standard-of-care therapies. Results from the Phase 2 Study of MM-121 in Combination with Exemestane in Metastatic ER/PR+, HER2 Negative Breast Cancer This randomized, double-blinded, placebo-controlled study evaluated whether the combination of MM-121 and exemestane was more effective in prolonging progression free survival (PFS) than exemestane in ER/PR+ mBC patients (n=118) who have previously failed anti-estrogen therapy. The estimated hazard ratio (HR) for PFS in the overall study population trended in favor of the MM-121 arm (HR 0.75; 95% CI [0.48 – 1.15]), although the primary endpoint of the study (HR < 0.5) was not met. Overall survival data also trended in favor of the MM-121 arm (HR 0.41; 95% CI [0.19 – 0.90]), but is at this point immature (~25% of patients). Analysis of a pre-specified set of biomarkers mechanistically linked to ErbB3 signaling revealed a subpopulation of patients (31% of the 55 biomarker-evaluable patients) in which the observed HR for PFS was 0.32 (95% CI [0.10-1.0]). The HR for PFS in the biomarker negative population was 0.89 [95% CI 0.44-1.79]. The undisclosed biomarkers identified in this study matched the two biomarkers previously reported for a study combining MM-121 with paclitaxel in women with platinum resistant ovarian cancer.
"The biomarker results of this study support the hypothesis that ErbB3 signaling is an important pathway of resistance for some breast and ovarian cancers," said Michaela Higgins, MD BCh, Assistant Professor of Medicine, Harvard Medical School and Massachusetts General Hospital Cancer Center and Principal Investigator on this study. "The data from this study suggest that MM-121 may enhance response to standard-of-care therapy among patients whose tumors are dependent on this pathway.""We are very pleased that the two biomarkers that we identified in this study are the same two biomarkers that identified a potential subpopulation of patients in our Phase 2 ovarian cancer trial. This serves to further confirm our original biomarker hypothesis. This also increases confidence in our diagnostic strategy to deliver therapies only to those patients who will most likely benefit from them," said Gavin MacBeath, Ph.D., Co-Founder and Vice President of Translational Research at Merrimack. "These data further implicate ErbB3 signaling as a general mechanism of resistance to standard-of-care therapies. We look forward to continued analysis of the biomarker data emerging from this clinical program and to working with our partners at Sanofi and our external advisors to identify the best path forward." Overall, similar frequencies were reported for adverse events of any grade between the treatment and control arms, with no unexpected toxicities experienced and no increase in serious adverse events (Grade 3 or worse adverse events were 55.2% on treatment arm vs. 53.1% on control arm). Increased frequencies for individual adverse events of all grades on the treatment arm were reported for diarrhea (50.0% vs. 23.7%), mucosal inflammation, (16.1% vs. 3.4%) and decreased appetite (16.1% vs. 8.5%). Most adverse events were mild-to-moderate in severity. There were no pulmonary embolisms or other venous thromboembolic events reported in either arm. Results from the Phase 2 Study of MM-121 in Combination with Paclitaxel in Neoadjuvant ER/PR+, HER2 Negative Breast Cancer This randomized, open-label Phase 2 study was designed to compare the pathologic complete response (pCR) rate in ER/PR+ breast cancer patients (n=99) treated in the neoadjuvant setting with MM-121 in combination with paclitaxel followed by doxorubicin and cyclophosphamide, with the pCR rate in patients receiving paclitaxel alone followed by doxorubicin and cyclophosphamide. pCR measures the absence of invasive cancer in breast and lymph node tissue following neoadjuvant therapy and is widely viewed as a strong indicator for prolonged disease-free survival.
Patients who received the combination of MM-121 and paclitaxel achieved a pCR rate of 10.8% (95% CI [5.3; 20.6]) compared to 3.3% (95% CI [0.6; 16.7]) for the control arm. There was no formal quantitative endpoint specified for this study. Extensive translational analysis is ongoing based on serial biopsies and will be reported in the future."These results are encouraging for the treatment of women with hormone receptor positive breast cancer who do not overexpress HER2," said Frankie Ann Holmes, MD, FACP of Texas Oncology, the Principal Investigator of the study. "Historically, these women have been very unlikely to achieve a pathologic complete response (pCR) with available chemotherapies. The hope is that pCR will be the signal that identifies women who may be cured with this new treatment. This is critical because there have been no major advances in the standard of care in more than a decade. I am looking forward to the results of the translational analysis across all patients which evaluates the role of growth factor dependent signaling in breast cancer. These findings will hopefully help us identify those patients that are more likely to achieve a pCR." Overall, similar frequencies were reported for adverse events of any grade between the treatment and control arms, with no unexpected toxicities experienced and no increase in serious adverse events (Grade 3 or worse events 25.0% on treatment arm vs. 25.4% on control arm). Increased frequencies for individual adverse events on the treatment arm were reported for diarrhea (82.1% vs. 34.4%), rash (41.8% vs. 15.6%), stomatitis (22.4% vs. 6.3%), and hypokalemia (29.9% vs. 6.3%). Most adverse events were mild-to-moderate in severity. In general, venous thromboembolic events were observed more frequently on the control arm (9.4%, including events of deep vein thrombosis and jugular thrombosis) than on the treatment arm (1.5%, one event of pulmonary embolism).
Merrimack will host a conference call at 8:00 a.m., Eastern time, today to discuss these results. Investors and the general public are invited to listen to the call by dialing (877) 564-1301 (domestic) or (224) 357-2394 (international) five minutes prior to the start of the call and providing passcode 16791357.About MM-121 MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor implicated in tumor growth and survival. By inhibiting ErbB3 signaling, MM-121 is designed to restore sensitivity, delay resistance and enhance the anti-tumor effect of a combination therapy partner. Sanofi and Merrimack entered into an exclusive, global license and collaboration agreement for MM-121 in 2009. About Merrimack Pharmaceuticals, Inc. Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack applies its systems biology-based approach to biomedical research throughout the research and development process. Merrimack currently has six oncology therapeutics in clinical development. For more information, please visit Merrimack's website at www.merrimackpharma.com. Forward-Looking Statement To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include any statements about Merrimack's strategy, future operations, future financial position and future expectations and plans and prospects for Merrimack, and any other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the potential effectiveness of MM-121 in combination with other therapies in certain patient populations or subpopulations, Merrimack's ability to develop a predictive diagnostic and Merrimack's ability to translate clinical data into future clinical success. Such forward-looking statements involve substantial risks and uncertainties that could cause Merrimack's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the initiation of future clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals and other matters that could affect the availability or commercial potential of Merrimack's drug candidates or companion diagnostics. Merrimack undertakes no obligation to update or revise any forward-looking statements. Forward-looking statements should not be relied upon as representing Merrimack's views as of any date subsequent to the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Merrimack's business in general, see the "Risk Factors" section of Merrimack's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 8, 2013 and other reports Merrimack files with the SEC.
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