FREMONT, Calif., Feb. 24, 2016 /PRNewswire/ -- Asterias Biotherapeutics, Inc. (NYSE: AST) today announced the successful completion of an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) for AST-VAC1, its investigational therapy targeting acute myeloid leukemia (AML).
During the meeting, the FDA indicated general agreement with Asterias' proposed development plan for registration of AST-VAC1 through a single Phase 3 trial to support an accelerated development pathway and Biologics License Application (BLA) filing. In this study, Asterias will assess the impact of AST-VAC1 compared to placebo on the duration of relapse-free-survival as the primary endpoint, and on overall survival as the secondary endpoint in patients who have achieved complete remission using standard therapies. The proposed trial will include AML patients 60 years and older, along with younger individuals who are at high risk for relapse and are not candidates for allogeneic bone marrow transplantation. Pending positive results, this trial could be the basis for accelerated approval of AST-VAC1. Asterias currently plans to submit a request for a Special Protocol Assessment (SPA) to the FDA to confirm the primary endpoint and other design elements of this pivotal Phase 3 trial.
"We are very pleased with the outcome of the End-of-Phase 2 meeting and the feedback from our discussion with the FDA," stated Pedro Lichtinger, President and Chief Executive Officer. "We believe the results from the Phase 2 clinical trial of AST-VAC1 in AML are encouraging. We appreciate the valuable guidance that the FDA has provided us regarding the design and conduct of a Phase 3 registration program and look forward to further discussions in the Special Protocol Assessment process."
About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is the most common type of acute leukemia and has the potential for rapid progression, if untreated. In AML, the bone marrow produces an excess number of immature cells known as blasts. In AML, these blasts fail to mature into normal red and white blood cells. Instead, the blasts proliferate and accumulate in the bone marrow and peripheral blood, leading to deficiencies in normal mature cells. These deficiencies, often referred to as cytopenias, can induce several adverse effects including anemias and susceptibility to infections. Current treatment strategies for AML are associated with significant morbidities and in most instances, AML leads to death.
Approximately 20,500 new cases of AML are diagnosed in the U.S. annually. AML remains a high unmet clinical need, particularly in patients over the age of 60 years who face poor outcomes and have limited therapeutic options. Treatment and prognosis in AML is strongly influenced by a patient's age and tumor profile. Successful treatment and survival of advanced age patients or those with a high risk profile is very poor, with a four year relapse-free survival of 10% – 20% (Rolig et al, 2011). Detailed characterizations of genetic abnormalities associated with AML have elucidated their high number and relative complexity, making development of targeted therapeutics to these mutations very challenging. For this reason, broad immunotherapy approaches such as autologous cell vaccines are particularly promising.
AST-VAC1 is a cancer immunotherapy, consisting of autologous mature antigen-presenting dendritic cells pulsed with a messenger RNA for the protein component of human telomerase (hTERT) and a portion of a lysosomal targeting signal (LAMP). hTERT is a common protein in tumor cells and is responsible for the increased proliferative lifespan of cancer cells. In AST-VAC1, the dendritic cells present telomerase to the immune system to induce T cells to target and kill hTERT-expressing tumor cells. The LAMP signal allows AST-VAC1 to stimulate both cytotoxic and helper T cell responses to telomerase, critical elements to induce and maintain immune responses that kill tumor cells. In June 2015, Asterias announced long-term follow-up results from a Phase 2 clinical trial in AML patients receiving AST-VAC1. In this trial, twenty-one patients received at least three injections of AST-VAC1, including 19 patients in complete remission (CR). AST-VAC1 showed a strong safety profile in this trial and in a previous study in prostate cancer patients. Eleven of the 19 patients (58 percent) in the trial remain in CR with a median duration of follow-up of 52 months from first vaccination. Four of the seven patients who were at least 60 years old at the time of immunotherapy with AST-VAC1 remained relapse-free 52 to 59 months from first vaccination.
Because of the widespread expression of telomerase in the majority of cancers, AST-VAC1 is a platform immunotherapeutic that could be used alone or in conjunction with other therapeutics such as immune checkpoint inhibitors to target immune-based destruction of tumors.
About Accelerated Approval
The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.
Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as Phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.
About Asterias Biotherapeutics
Asterias Biotherapeutics, Inc. is a leading biotechnology company in the emerging field of regenerative medicine. The company's proprietary platforms are based on its pluripotent stem cell and dendritic cell immunotherapy technologies. Asterias is focused on developing therapies to treat conditions in several medical areas where there is high unmet medical need and inadequate available therapies. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) has demonstrated promise in a Phase 2 study in acute myeloid leukemia. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic approach to dendritic cell vaccines. Additional information about Asterias can be found at www.asteriasbiotherapeutics.com.
Forward Looking Statements
Statements pertaining to future financial and/or operating results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias's filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.
SOURCE Asterias Biotherapeutics, Inc.