Breast cancer is the most commonly diagnosed malignancy and one of the major causes of death among women. It is also one of the most investigated diseases, but its biological features are still not well understood. The number of breast cancer cases in US in 2011 include 232,620 cases with 17% of those ending in death, totaling 39,970. Men compose only 450 of those cases. To put this in perspective, the number of new cancers in the United States totals 1,596,670 for 2011. The American Cancer Society (ACS) says about 20% of breast cancer survivors who have completed 5 years of additional cancer treatment will experience recurrence within 10 years following treatment, but this statistic is highly dependent on many factors such as the stage of disease, the cancer grade and hormone receptor status.
Despite this, due to the successful promotion of earlier breast cancer screening techniques and the improvement of therapeutic strategies, breast cancer mortality has been falling steadily since the 1990s. Several effective treatment strategies having been explored in dealing with different types of advanced breast cancer, such as endocrine therapy and molecular targeted therapy. The current standard of care for therapeutics consists, in general, of chemotherapy, hormone therapy and targeted therapies. On the market, there are approximately 47 chemotherapeutic drugs approved by the FDA for the treatment of breast cancer with 8 classified as targeted therapeutics. Targeted cancer therapeutics are drugs that block the growth and spread of cancer by interfering with specific molecules or receptors involved in tumor growth and progression. The earliest of these targeted therapies were selective estrogen receptor modulators which included drugs like Tamoxifen and Faslodex®, from AstraZeneca (AZN); and toremifene (Fareston®), from GTx, Inc., (GTXI).
HER2: A Blockbuster Target: Human epidermal growth factor receptor 2 (HER-2) is a protein that sends control signals into cells, telling them to grow, divide, and make repairs. A healthy breast cell has 2 copies of the HER2 gene. Some kinds of breast cancer get started when a breast cell has more than 2 copies of that gene, and those copies start over-producing the HER2 protein. As a result, the affected cells grow and divide much too quickly because with too many receptors, the cells receive too many growth signals. Thus, HER2 and its signaling pathway have received widespread attention in the development of therapeutic products.
The monoclonal antibody Trastuzumab (Herceptin®) from Roche (OTC:RHHBY), is a successful example of this. Herceptin is effective only in cancers where HER2 is highly over-expressed in the cancer cells. The next version of this therapeutic approach is currently in advanced clinical trials. This product is the monoclonal antibody, Pertuzumab (Roche), which works differently by inhibiting dimerization of HER2 and HER3 receptors.
A third, Lapatinib (Tykerb®) from GlaxoSmithKline (GSK), is an orally active drug for breast cancer and other solid tumors approved in 2007. It is a tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. It is used in combination therapy for HER2-positive breast cancer and is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2.
Breast Cancer Treatment Options: If a patient's breast cancer is tested for HER2 status, the results will be graded as positive or negative. The test gives a score of 0, 1+, 2+ or 3+ which indicates the amount of HER2 receptor protein on the cells in a sample of breast cancer tissue. If the tissue scores 0 to 2+, it's typically called "HER2 negative or borderline." If it scores 3+, it's called "HER2 positive." If results are graded as HER2 positive, this means that HER2 genes are significantly over-producing the HER2 protein, and that those cells are growing rapidly and creating the cancer. If your results are graded HER2 negative, then the HER2 protein may be expressed but at a lower level and treatment of the cancer may be more achievable.
An Unmet Need in Breast Cancer Therapeutics: Currently, no approved antibody-based therapy is available for breast cancer patients with low HER2 expression (1+ or 2+). NeuVax™ (E75) Galena Biopharma (GALE) is focused on the development of innovative, targeted oncology drugs to address major unmet medical needs and advance cancer care in this area. NeuVax™ (E75 peptide plus GM-CSF) is a novel immunotherapy that directs the immune system to target and destroy cancer cells that express HER2. NeuVax™ is a vaccine specifically for HER2 1+ and 2+ breast cancer patients (often referred to as HER2 negative) to prevent recurrence of the disease. To size this population, of all breast cancer patients diagnosed in the United States; HER2 (0, 1+, 2+ or 3+), only 25% of these are scored HER2 3+, making them eligible for Herceptin® (trastuzumab; Roche-Genentech), which achieved revenues approaching $6 billion in 2011.
In comparison, 50% of all breast cancer patients have tumors that are HER2 1+ or 2+. NeuVax™ targets this 50% of HER2 patients (HER2 1+ and 2+) who achieve remission with current standard of care, but have no available HER2-targeted adjuvant treatment options to maintain their disease-free status. This is a well-recognized unmet need. For these patients, they are typically successfully rendered disease-free following treatment with the current standard of care, and then must wait with the hope their cancer never returns. Thus, the results from the NeuVax™ phase I/II clinical trial show that NeuVax™ provides a benefit to maintain disease-free survival in these patients who have no other treatment options.
In this study of 187 patients, 108 received vaccine and 79 did not (control group). Patients enrolled in the trial were node positive or high-risk node negative breast cancer patients with any level of HER2 expression (1+, 2+, or 3+), and rendered disease-free after standard adjuvant therapies. With follow-up over an average of 60 months, the NeuVax™ treated group experienced a 10.6% recurrence rate compared to 20.3% in the control group which is a 48% risk reduction (p=0.098).
This encouraging result has allowed the drug to proceed to a Phase III multinational trial which will be conducted in approximately 700 breast cancer patients who have low or intermediate HER2 expression (HER2 negative). As stated, in most cases, these patients are not eligible to receive Herceptin® therapy that is currently approved only for HER2 positive patients. If the Phase III clinical trial achieves similar results to the Phase I/II trial, this could very easily be a blockbuster drug with significant adoption in a large number of patients.