Merrimack Pharmaceuticals Inc. Presents Additional Phase 2 Biomarker Data Further Strengthening The Finding That MM-121 Increases Progression Free Survival In Patients With Biomarker Positive Metastatic Breast Cancer
Data Presented as Part of Meta-Analysis Showing MM-121's Favorable Impact on Progression Free Survival in 38-54 Percent of Patients With Ovarian, Lung and Breast Cancers Across Three Phase 2 Studies
Clinical and Biomarker Data From Phase 1 Studies of MM-151 and MM-111 Presented; MM-151 Wins "Best Poster" in Developmental Therapeutics Poster Session
MADRID, Spain, Sept. 30, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) announced today additional clinical and biomarker data from a Phase 2 study in ER/PR-positive, HER2-negative metastatic breast cancer showing that patients with high heregulin mRNA levels achieved a statistically significant benefit from combining the novel agent MM-121 with exemestane. Updated data from this biomarker subgroup, representing 45% of patients with metastatic breast cancer, showed a hazard ratio of 0.26 with a p-value of 0.003.
The data were presented at the European Society of Medical Oncology (ESMO) 2014 Congress as part of a meta-analysis of the biomarker data from three Phase 2 studies of MM-121 in combination with standard-of-care agents across breast, lung and ovarian cancers.
"As additional biomarker data have recently become available, it is encouraging that they are consistent with our previous observations and further strengthen our hypothesis that heregulin-driven ErbB3 signaling desensitizes tumors to standard-of-care therapies and that MM-121 has the ability to counteract this mechanism in patients who have become insensitive to therapy," said Gavin MacBeath, PhD, Co-Founder and Senior Vice President at Merrimack Pharmaceuticals. "At Merrimack, we believe MM-121 may one day provide an important treatment option for patients that are HER2 negative with high heregulin levels and look forward to advancing its clinical development targeting patients with this specific biomarker profile."
MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. In Q2 2014, Merrimack regained worldwide rights to MM-121 and is pursuing a partnership to support the continued development of the program.
"These new data underscore the importance of ErbB3 and the enormous medical need and opportunity for MM-121," said Robert Mulroy, President and CEO of Merrimack Pharmaceuticals. "The prevalence data across the 800 patient Phase 2 program supports our initial hypothesis that MM-121 has the potential to play an essential role in the improved treatment of hundreds of thousands of patients in the US alone, representing up to one third to one half of solid tumors. We are pleased to be on the forefront of the effort to combat resistance for the benefit of patients."
Clinical and biomarker data were also presented from Phase 1 studies of MM-151, and MM-111.
Methodology and Results:
Results from a Meta-Analysis of Biomarkers in Three Randomized, Phase 2 Studies of MM-121 in Patients with Ovarian, Lung, and Breast Cancers
To access the MM-121 clinical poster presented at ESMO 2014, click here.
Previous results from the MM-121 Phase 2 program presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting identified high heregulin mRNA as prognostic of poor response to standard-of-care therapy across multiple cancers. These results also showed that patients with heregulin-high tumors experienced a reduction in their risk of progression when they received a combination of MM-121 with their standard-of-care therapy as compared to patients who received the standard therapy alone. The previous analysis included 55 patients with breast cancer, 17 of whom were biomarker positive. The poster presented at ESMO 2014 provides biomarker data on 76 ER/PR positive, HER2-negative patients with metastatic breast cancer, 34 of whom were biomarker positive (heregulin-high). The poster also provides the first cross-indication analysis of biomarker data from platinum-resistant ovarian cancer, ER/PR+ HER2- breast cancer and EGFR wild-type non-small cell lung cancer.
Biomarker data across the three studies are as follows:
| Study | Biomarker Positive* | |||
| No. of Patients | Hazard Ratio | Prevalence | P-Value | |
| Breast | 34 | 0.26 (95% CI [0.11-0.63]) | 45% | 0.003 |
| Ovarian | 57 | 0.37 (95% CI [0.18-0.76]) | 38% | 0.007 |
| Lung | 37 | 0.35 (95% CI [0.16-0.76]) | 54% | 0.008 |
* Biomarker positive is defined as heregulin-high in the breast and lung studies, and heregulin-high, HER2-low in the ovarian study.
- Heregulin is a potential biomarker for insensitivity to standard-of-care therapy and a predictor of clinical benefit in late-stage ovarian, lung, and breast cancers.
- An additional 17 biomarker positive patients with metastatic breast cancer were included in this study analysis. Patients in this population with high heregulin levels have a greater risk of disease progression on standard-of-care therapy compared than those who have low heregulin levels. With the addition of MM-121 to standard-of-care therapy, however, patients with high heregulin levels have a significantly reduced risk of progression (PFS HR 0.26, 95% CI [0.11-0.63]).
- There was a consistent but modest and tolerable increase in adverse events when MM-121 was combined with the three different standard-of-care regimens.
Updated Results from a Phase 1 Trial of MM-151 in Patients with Refractory Solid Tumors
("Best Poster" Winner for Developmental Therapeutics Poster Session)
To access the MM-151 clinical poster presented at ESMO 2014, click here.
MM-151 is a novel oligoclonal anti-EGFR antibody combination designed to target EGFR-driven tumor growth. Updated data from a Phase 1 study in patients with refractory solid tumors show that MM-151 alone and MM-151 in combination with irinotecan has a manageable safety profile and preliminary clinical activity in colorectal cancer.
- Monotherapy safety is consistent with expected EGFR toxicities and combination safety is consistent with known EGFR and irinotecan toxicities.
- Encouraging clinical activity was observed in these heavily pre-treated solid tumor patients, including those with prior cetuximab therapy and particularly in EGFR-related subtypes such as colorectal, non-small cell lung and head and neck cancers. Partial responses (PR) were observed in 6 patients in total.
- A recommended Phase 2 dose of has been defined for the weekly monotherapy schedule
Biomarker analysis from a Phase 1, multi-arm study of MM-111 in combination with standard of care regimens in patients with advanced HER2-positive solid tumors
To access the MM-111 clinical poster presented at ESMO 2014, click here.
MM-111 is a bispecific antibody designed to inhibit HER3 (ErbB3) signaling in HER2-positive tumors. Preclinical research has shown that MM-111 may restore sensitivity to chemotherapy and HER2-targeted treatment when tumors have become resistant to these therapies.
- Archived tumor tissue samples were used to assess a panel of five pre-specified biomarkers, identified by Merrimack's systems biology approach and confirmed in preclinical studies. These biomarkers are HER2, HER3, heregulin, EGFR, and betacellulin.
- The sensitivity and specificity of the assays developed to measure biomarkers in the Phase 1 study supports the use of these assays for the analysis of samples from an ongoing randomized Phase 2 study of MM-111 in HER2-positive gastro-esophageal cancer. This study has two primary endpoints. The first being PFS in the total population and the second being PFS in patients with high heregulin levels. The biomarker assays are identical to the ones used in the biomarker analysis in three Phase 2 studies for MM-121.
About Merrimack
Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack seeks to gain a deeper understanding of underlying cancer biology through its systems biology-based approach and develop new insights, therapeutics and diagnostics to improve outcomes for cancer patients. Merrimack currently has six oncology therapeutics in clinical development and three additional candidates in late stage preclinical development. Merrimack's lead product candidate, MM-398, recently completed a Phase 3 trial in post-gemcitabine pancreatic cancer. Based on the results of this trial, Merrimack intends to file a New Drug Application for MM-398 in 2014. For more information, please visit Merrimack's website at www.merrimackpharma.com or connect with us on Twitter at @MerrimackPharma.
Forward-Looking Statements
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," "hope" and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the potential effectiveness and tolerability of its investigational therapeutics in certain patient populations or subpopulations, its ability to develop a predictive diagnostic, the initiation of future clinical studies, the timing of submitting a New Drug Application to the FDA and its 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, availability of data from ongoing clinical trials, expectations for regulatory approvals, development progress of Merrimack's companion diagnostics 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 August 11, 2014 and other reports Merrimack files with the SEC.
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