VANCOUVER, BC and MENLO PARK, CA--(Marketwired - August 21, 2013) - DelMar Pharmaceuticals, Inc. (OTCQB: DMPI) ("DelMar") today announced that the company has received a notice of allowance from the United States Food and Drug Administration (FDA) that will enable the company to accelerate the dose-escalation of its ongoing Phase I/II of VAL-083 in refractory glioblastoma multiforme (GBM) patients.
The revised dosing regimen was allowed by the FDA following an extensive safety review of patients treated to date. In comparison to the original dose-escalation scheme, the revised plan will enable the trial to reach higher doses and complete the dose-escalation portion of the clinical trial more quickly by skipping two interim doses:
Original dose-escalation Revised dose-escalation
10 mg/m2 10 mg/m2
20 mg/m2 20 mg/m2
30 mg/m2 30 mg/m2
The revised dosing scheme also permits dosing above 30mg/m2 if VAL-083 is safe and well-tolerated at that dose.
"We are very pleased that the FDA has accepted the proposed revisions to our dosing-escalation protocol," said Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals. "Glioblastoma multiforme is one of the most difficult tumors to treat, affecting approximately 15,000 patients in the United States each year. Clinical management of recurrent GBM is particularly challenging. Based on available data, we believe that VAL-083 may offer new treatment options for patients suffering from both refractory and newly diagnosed GBM who are unlikely to respond to or have failed currently available therapies."
DelMar reported data on the first three cohorts (1.5mg/m2, 3mg/m2 and 5.0mg/m2) at the American Society for Clinical Oncology (ASCO) in June 2013. Results reported to date have shown promising drug activity in brain tumor patients who have failed or are unlikely to benefit from the standard of care, even at doses much lower that used in historical clinical studies sponsored by the National Cancer Institute in the United States. Pharmacokinetic analysis shows dose-dependent increases in plasma exposure following doses of VAL-083. Based on the linearity of the pharmacokinetic data, enhanced response rates may be expected at higher doses. At ASCO, DelMar also announced that going forward, the current trial will focus on GBM and a separate protocol for secondary brain tumors will be developed.
"The safety of VAL-083 based on historical clinical studies has been validated at the doses tested to date in our clinical trial. Based on the results we've observed to date, we approached the FDA about focusing the current study on GBM and altering the dose-escalation scheme to enable the trial to proceed more quickly," stated Mr. Bacha. "Accelerating the program will enable us to complete the dose-escalation portion of our clinical trial, attain doses that are more likely to have anti-tumor effects and advance into registration-directed studies for refractory GBM in the timeliest manner possible. Our goal remains to complete the dose-escalation during 2013 and be prepared to advance into registration-directed trials in 2014."
VAL-083 represents a 'first-in-class' small-molecule chemotherapeutic. VAL-083 has been assessed in multiple NCI-sponsored clinical studies in various cancers including lung, brain, cervical, ovarian tumors and leukemia. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types. VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer.
Based on published research, the mechanism of action of VAL-083 is understood to be a bi-functional alkylating agent; however, the functional groups associated with alkylating events has been shown to differ from other alkylating agents used in the treatment of GBM.
VAL-083 has previously demonstrated activity in cyclophosphamide, BCNU and phenylanine mustard resistant cell lines and no evidence of cross-resistance has been encountered in published clinical studies. Based on the presumed alkylating functionality of VAL-083, published literature suggests that DNA repair mechanisms associated with Temodar® and nitrosourea resistance, such as 06-methylguanine methyltransferase (MGMT), may not confer resistance to VAL-083.
VAL-083 readily crosses the blood brain barrier where it maintains a long half-life in comparison to the plasma. Published preclinical and clinical research demonstrates that VAL-083 is selective for brain tumor tissue.
VAL-083 has been assessed in multiple studies as chemotherapy in the treatment of newly diagnosed and recurrent brain tumors. In general, tumor regression was achieved following therapy in greater than 40 percent of patients treated and stabilization was achieved in an additional 20 to 30 percent. In published clinical studies, VAL-083 has previously been shown to have a statistically significant impact on median survival in high-grade gliomas when combined with radiation versus radiation alone.
The main dose-limiting toxicity related to the administration of VAL-083 in previous clinical studies was myelosuppression. No significant hepatic, renal or pulmonary toxicity has been reported in the literature or overseas commercial experience.
About Glioblastoma Multiforme (GBM)
GBM is the most common and most malignant form of brain cancer. Of the estimated 17,000 primary brain tumors diagnosed in the U.S. each year, approximately 60 percent are gliomas. Attention was drawn to this form of brain cancer when Senator Ted Kennedy was diagnosed with glioblastoma in 2008 and ultimately died from the disease fifteen months later.
Newly diagnosed patients suffering from GBM are initially treated through invasive brain surgery, although disease progression following surgical resection is nearly 100 percent. Temodar in combination with radiation is the front-line therapy for GBM following surgery. Temodar currently generates more than US$950 million annually in global revenues primarily from the treatment of brain cancer.
Approximately 60 percent of GBM patients treated with Temodar experience tumor progression within one year. Avastin® has been approved for the treatment of GBM in patients failing Temodar. According to the Avastin label, approximately 20 percent of patients failing Temodar respond to Avastin therapy. Analysts anticipate annual Avastin revenues for the treatment of brain cancer may reach US$650 million by 2016.
Approximately 48 percent of patients who are diagnosed with GBM will fail both front-line Temodar therapy and Avastin. DelMar estimates that the market for treating GBM patients the post-Avastin failure exceeds US$200 million annually in North America.
About the VAL-083 Clinical Trial
The Phase I/II study is an open-label, single arm dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of VAL-083 in patients with histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (GBM), now recurrent. Patients with prior low-grade glioma or anaplastic glioma are eligible, if histologic assessment demonstrates transformation to GBM.
GBM patients must have been previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both Avastin and Temodar, unless either or both are contra-indicated.
Response to therapy and disease progression will be evaluated by MRI prior to each treatment cycle. An initial phase of the study will involve dose-escalation cohorts until a maximum tolerated dose (MTD) is established in the context of modern care. Once the modernized dosing regimen has been established, additional patients will be enrolled at the MTD (or other selected optimum dosing regimen).
DelMar is currently conducting the study at three clinical sites including the University of California, San Francisco, the Sarah Cannon Research Institute in Nashville, Tennessee and at the Florida Cancer Specialists & Research Institute in Sarasota, Florida.
Please refer to clinicaltrials.gov identifier NCT01478178 for further details on this clinical trial or visit: http://www.clinicaltrials.gov/ct2/show/NCT01478178?term=VAL--083&rank=1
About DelMar Pharmaceuticals
Del Mar Pharmaceuticals was founded in 2010 to develop and commercialize proven cancer therapies in new orphan drug indications where patients are failing modern targeted or biologic treatments. The Company's lead asset, VAL-083, is currently undergoing clinical trials in the United States as a potential treatment for refractory glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. VAL-083 benefits from extensive clinical research sponsored by the U.S. National Cancer Institute, and is currently approved for the treatment of chronic myelogenous leukemia (CML) and lung cancer in China. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types via a novel mechanism of action.
Safe Harbor Statement
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. Any forward-looking statements contained herein are based on current expectations, but are subject to a number of risks and uncertainties. The factors that could cause actual future results to differ materially from current expectations include, but are not limited to, risks and uncertainties relating to the Company's ability to develop, market and sell products based on its technology; the expected benefits and efficacy of the Company's products and technology; the availability of substantial additional funding for the Company to continue its operations and to conduct research and development, clinical studies and future product commercialization; and, the Company's business, research, product development, regulatory approval, marketing and distribution plans and strategies. These and other factors are identified and described in more detail in our filings with the SEC, including, our current reports on Form 8-K. We do not undertake to update these forward-looking statements made by us.