Skip to main content
Premium Trial:

Request an Annual Quote

Acceleron Exploring New Biomarker Leads to Personalize Treatment for Breast, Head and Neck Cancers


Acceleron Pharma recently presented data on two biomarkers that the company is exploring as part of its strategy to advance personalized drugs for breast and squamous cell head and neck cancer patients.

At the American Society of Clinical Oncology's recent 2012 Markers in Cancer conference, researchers from Acceleron and elsewhere presented data from a study in which patients who had elevated serum levels of the protein activin lived for a shorter time after treatment with Herceptin-containing therapies than those with low levels of the protein.

Activin A regulates how cells proliferate, die, and differentiate, as well as their immune responses. Data from the study suggests that a test measuring activin A levels may be able to gauge which breast cancer patients have a worse outcome, are at heightened risk for Herceptin resistance, and might respond more favorably to drugs targeting both activin A and HER2. Acceleron is working with Celgene to develop drugs targeting activin A.

Another study presented at the same meeting investigated how three squamous cell head and neck cancer patients responded to dalantercept, an investigational protein therapeutic that hinders the formation of new blood vessels that drive tumors. Specifically, the drug keeps ligands BMP9 and BMP10 from binding with the cell surface receptor activin receptor-like kinase 1, or ALK1. In this way, dalantercept "inhibits ALK1 signaling, a pathway distinct from that of the VEGF signaling pathway, which is required for the development of mature, functional vasculature" that tumors need to survive, an Acceleron spokesperson told PGx Reporter.

In the Phase I study reported at the meeting, Acceleron didn't use a biomarker-driven strategy to personalize treatment with dalantercept. However, two out of the three patients receiving the drug responded. One patient receiving the drug for 30 weeks at 0.4 mg/kg saw a 32.5 percent decrease in lesion size; a second patient received 33 weeks of treatment at 1.6 mg/kg and had a 28.9 percent decrease in lesion size; and a third patient had progressive disease after 1 cycle of treatment at 0.8 mg/kg.

Following this early investigation, researchers from Acceleron have decided to investigate in a Phase II trial how BMP9 expression assessed through patients' tumor tissue and in serum correlate with dalantercept response. They noted in their abstract that analysis of archived tumors samples from squamous cell head and neck cancer patients have revealed that 25 percent of patients have high BMP-9 expression and 44 percent had medium levels of expression.

"Acceleron and our partners are interested in exploring avenues that will help improve patients’ therapy options and outcomes, including potential companion diagnostic tools," the company spokesperson said, referring to the company's efforts to develop activin A-targeting drugs and dalantercept . "We’re internally developing the assays and, at the appropriate time, would anticipate working with a partner on a diagnostic tool."

Activin A in Breast Cancer

In the first study, researchers led by Lindsey Zubritsky of Penn State Hershey College of Medicine measured activin A serum levels in 60 metastatic breast cancer patients using an ELISA assay before they were treated with a Herceptin-containing regimen. Roche/Genentech's Herceptin is a drug for metastatic breast cancer patients who overexpress the HER2 protein. Although around 20 percent of invasive breast cancers overexpress HER2, even in this patient subset, only half of the HER2-positive patients respond to Herceptin, and most of these patients will experience disease progression within a year.

The study conducted by Zubritsky and colleagues showed that patients with high pre-treatment levels of serum activin A had lower median progression-free survival than those with low levels of this protein serum ─ 6.6 months compared to 31.1 months ─ after receiving Herceptin-containing regimens. Median overall survival was shorter, too, in those with high activin A levels (19.6 months), while the median overall survival level hadn't been reached yet among those with low levels of the protein when the study data were reported.

When researchers compared the prognostic strength of activin A to other factors, such as patients' age, line of therapy, hormone receptor status, and whether they overproduce the CA15-3 tumor marker, activin A was the only significant predictor of progression-free survival. Meanwhile, activin A and CA 15-3 levels were found to be significant prognostic factors for overall survival in the study.

"Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy," Zubritsky and colleagues concluded. "Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy."

Acceleron has partnered with Celgene to develop sotatercept, which is "an activin receptor type IIA" receptor fusion protein, and other activin antagonists. "Based on this biomarker data and data we have seen on activin A antagonists in preclinical models of breast cancer, the two companies are discussing how best to pursue this exciting opportunity," the Acceleron spokesperson said.

Although further investigation is required to confirm this finding, this data suggest that testing for activin A, in addition to HER2, may help improve breast cancer patients' outcomes with an agent targeting both proteins. "Based on the data in this abstract, one possible approach would be to prospectively select patients that are HER2 positive and have high serum activin A levels and treat these patients with drugs that target both HER2 and activin A rather than take a strategy in which a physician would wait for patients to fail HER2 treatment and then try to intervene with a second line agent," the Acceleron spokesperson said.

Squamous Cell Head and Neck Cancer

In the Phase II trial for dalantercept, meanwhile, Acceleron is primarily interested in seeing how many squamous cell head and neck cancer patients experience an objective response – either a complete or partial response – to the drug. Researchers led by Scott Pearsall, director of preclinical pharmacology at Acceleron, will also track patients' progression-free survival, overall survival, safety, tolerability, and pharmacokinetics following treatment.

Study investigators will also perform biomarker analysis as part of this Phase II trial. They will examine BMP9 expression in study participants, as well as other markers, to gauge whether they are associated with differential response to dalantercept. If such markers are found, Acceleron will consider launching the drug with a companion diagnostic to identify best responders.

Standard treatment for squamous cell head and neck cancer patients includes surgery, as well as a combination of chemotherapy and radiation treatment. Bristol-Myers Squib/Merck Serono/Lilly's Erbitux (cetuximab) is approved as a treatment for squamous cell head and neck cancer as a single agent or in combination with radiation therapy or platinum-based therapy.

"If proven successful in clinical trials, dalantercept could provide another therapy option for patients with recurrent or metastatic SCCHN, potentially alone or in combination with an existing method of treatment," the Acceleron spokesperson said. Acceleron cited data from the Human Protein Atlas Database showing that 75 percent of head and neck cancer biopsies had moderate or high expression of BMP9 as measured by immunohistochemical staining.

Upon the successful completion of the Phase II trial for dalantercept, the company expects to begin a Phase III study sometime in 2014.

The Scan

Ancient Greek Army Ancestry Highlights Mercenary Role in Historical Migrations

By profiling genomic patterns in 5th century samples from in and around Himera, researchers saw diverse ancestry in Greek army representatives in the region, as they report in PNAS.

Estonian Biobank Team Digs into Results Return Strategies, Experiences

Researchers in the European Journal of Human Genetics outline a procedure developed for individual return of results for the population biobank, along with participant experiences conveyed in survey data.

Rare Recessive Disease Insights Found in Individual Genomes

Researchers predict in Genome Medicine cross-population deletions and autosomal recessive disease impacts by analyzing recurrent nonallelic homologous recombination-related deletions.

Genetic Tests Lead to Potential Prognostic Variants in Dutch Children With Dilated Cardiomyopathy

Researchers in Circulation: Genomic and Precision Medicine found that the presence of pathogenic or likely pathogenic variants was linked to increased risk of death and poorer outcomes in children with pediatric dilated cardiomyopathy.