|Provectus's PV-10 Path to Initial Approval in U.S.; Pfizer Announces Results From Two Phase 3 Trials Of Dacomitinib|
|By Staff and Wire Reports|
|Monday, 27 January 2014 20:02|
Provectus Biopharmaceuticals, Inc. (OTCMKTS:PVCT), a development-stage oncology and dermatology biopharmaceutical company, today announced that it has received the official minutes from the Type C meeting held with the FDA’s Division of Oncology Products 2 on December 16, 2013. The purpose of the meeting was to determine which of the available paths that Provectus's novel investigational oncology drug PV-10 will take in pursuit of initial FDA approval and commercialization. PV-10, a 10% solution of rose bengal disodium, is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, while inducing a secondary tumor-specific immune response. As a result of this meeting, Provectus will submit data from its Phase 2 study in a formal breakthrough therapy designation (BTD) request this quarter, and should receive a decision within 60 days of receipt of that request.
With the passage of the Food and Drug Administration Safety and Innovation Act (FDASIA) in July 2012, the Food and Drug Administration (FDA) was given powerful expedited tools to speed patient access to innovative medicines for serious or life-threatening conditions (Food and Drug Administration Safety and Innovation Act (FDASIA)). FDASIA initiatives such as breakthrough therapy designation are designed to accelerate approval for new drugs that show preliminary clinical evidence of a large treatment effect. A key feature of BTD authorizes the Agency to take steps to ensure that the design of the clinical trials are as efficient as practicable, when scientifically appropriate, such as by minimizing the number of patients exposed to a potentially less efficacious treatment. Requests for BTD are reviewed and granted or rejected within 60 days of receipt. As Provectus has previously reported, based on rapid tumor destruction in a positive Phase 2 trial in melanoma patients receiving PV-10 (protocol PV-10-MM-02), input from the Agency regarding the current development plan was sought. Agency guidance (Frequently Asked Questions: Breakthrough Therapies) encourages sponsors to seek such advice prior to formal request for designation.
Chief Executive Officer Craig Dees, Ph.D., observed, “This meeting with the FDA is another significant step forward in streamlining the pathway to initial U.S. approval of PV-10 as the first local agent for recurrent locoregionally advanced melanoma. These patients suffer with troublesome, disfiguring disease that can persist for many years before presenting at distant sites. Our meeting with the Agency established the parameters for submission of a BTD request tailored to addressing the pressing needs of these patients. We’re grateful that our work with the Agency, in this and in our previous meetings, to identify a strategy for demonstration of clinical benefit in recurrent patients is bearing fruit. We are very pleased that the path to initial approval in the U.S. is now clear and PV-10 can be available to help patients in a more condensed time frame than if the Agency required an overall survival endpoint in a large randomized Phase 3 study.”
The meeting and official meeting minutes provided valuable guidance on a number of issues surrounding the approval path of PV-10:
The Phase 2 study of PV-10 showed:
These data show that if a tumor is accessible to PV-10 injection, the drug is likely to destroy that tumor. If approved, PV-10 would be the first tissue-sparing local therapy for recurrent melanoma.
Dees continued, “The Agency may yet recommend and it may be in the best interest of Provectus to undertake a small, short bridging study in patients where all tumor burden can be injected. This would allow more frequent dosing than was permitted in the Phase 2 study, presumably akin to the dosing schedule currently used to treat nearly 100 patients under our expanded access protocol, and allow symptomatic endpoints to be prospectively correlated with objective response criteria. Provectus has $18 million in cash reserves and would not require additional capital or the resources of a partner to conduct such a study. If such a study is conducted, it also fits with needs for an international study supportive of licensure in Australia, Europe, China and India.”
Dees further stated, “Non-specific local treatments that temporarily reduce tumor burden, such as surgery and radiation, are the most commonly used cancer therapies today. Furthermore, we believe our clinical and immunologic mechanism data show that it may be possible to delay or prevent melanoma metastasis to distant sites.”
Dees continued, “Measurement of tumor shrinkage via objective response criteria has been considered direct clinical benefit in drug approvals for other skin cancers and we believe a similar case can be made for PV-10 in locally advanced cutaneous melanoma. As advised by the Agency, we will submit data from the 28 patients in our Phase 2 study who had all existing disease treated in a formal BTD request this quarter, and should receive a decision within 60 days of receipt of that request.”
Dees concluded, “While the rapid ablative effect immediately evident in patients treated with PV-10 highlights our path to initial approval, the bystander effect continues to be of scientific interest and studies to quantify systemic tumor-specific immune response in cancer patients are ongoing. This emerging understanding of the secondary effect of tumor ablation with PV-10 is an important foundation for future studies to assess the long-term impact of PV-10 on distant metastasis and possible combination strategies for use of PV-10 in the treatment of cancer patients with more advanced disease.”
Pfizer Inc. (NYSE:PFE) announced top-line results from two randomized Phase 3 studies of the irreversible pan-HER kinase inhibitor dacomitinib in patients with advanced non-small cell lung cancer (NSCLC).
Both trials evaluated dacomitinib in populations of previously treated patients with advanced NSCLC. The ARCHER 1009 trial, which included patients previously treated with chemotherapy (second/third line), did not meet its objective of demonstrating statistically significant improvement in progression-free survival (PFS) when compared with the EGFR inhibitor erlotinib.
Separately, the NCIC CTG BR.26 trial, which included patients with advanced NSCLC after standard therapy with both chemotherapy and an EGFR tyrosine kinase inhibitor had failed, did not meet its objective of prolonging overall survival (OS) versus placebo.
An ongoing, third Phase 3 trial, ARCHER 1050, is evaluating PFS of dacomitinib in a different patient population than was studied in ARCHER 1009 and BR26. ARCHER 1050 compares dacomitinib versus gefitinib in treatment-naïve (without prior treatment) patients with EGFR-mutant advanced NSCLC. The results are expected in 2015.
“While we are disappointed in the results, lung cancer is a complex disease, and the use of targeted agents to treat specific patient populations continues to evolve,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology. “We are analyzing the findings from both ARCHER 1009 and BR.26 to better understand the effects of dacomitinib in molecularly defined subgroups of patients with advanced NSCLC, including those with EGFR mutations.”
The ARCHER 1009 trial evaluated dacomitinib versus erlotinib in two co-primary populations of patients with advanced NSCLC previously treated with at least one chemotherapy regimen – all patients and patients with KRAS wild-type NSCLC. The study did not demonstrate that dacomitinib improved PFS in either of the co-primary populations compared to erlotinib.
The BR.26 trial was a double-blind, placebo-controlled, randomized study evaluating dacomitinib in patients with locally advanced or metastatic NSCLC after prior treatment, which included at least one chemotherapy regimen and one EGFR inhibitor treatment regimen. This study was designed, conducted and led by NCIC Clinical Trials Group (NCIC CTG).
“We are pleased to have had the opportunity to assess dacomitinib in the BR.26 trial,” said Dr. Peter Ellis, BR.26 Study Chair and Associate Professor in the Department of Oncology, McMaster University, and medical oncologist at the Juravinski Cancer Centre, Hamilton, Ontario, Canada. “While we are disappointed that the trial did not meet its primary endpoint, we are supportive of Pfizer’s commitment to continue to evaluate dacomitinib in the ARCHER 1050 trial.”
In both studies, the adverse events observed for dacomitinib generally were consistent with its known adverse event profile. Full efficacy and safety data from ARCHER 1009 and BR.26 will be submitted for presentation at an upcoming medical meeting.
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