--Implications For Special Protocol Assessment For Phase 3 Trial Of PV-10--
KNOXVILLE, Tenn.--(BUSINESS WIRE)-- Provectus Pharmaceuticals, Inc. (OTC BB: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company, announced that final top-line data from its Phase 2 clinical trial of PV-10 for metastatic melanoma were presented at the ESMO (European Society for Medical Oncology) 2012 Congress in Vienna, Austria on October 1, 2012. The data were presented in Poster Presentation III, Abstract #1137P, "Immuno-chemoablation of metastatic melanoma with intralesional rose bengal." The poster was presented by Dr. Sanjiv Agarwala, M.D., Principal Investigator for the Phase 2 trial of PV-10, and Chief of Medical Oncology and Hematology at St. Luke's Hospital and Health Network in Bethlehem, PA. The poster was authored by Dr. Agarwala along with co-authors J.F. Thompson, B.M. Smithers, M. Ross, B.J. Coventry, D.R. Minor, C.R. Scoggins and E. Wachter.
The data presented on response rate and progression free survival corroborated previously presented preliminary data on these topics. Key results include:
- An Objective Response Rate (OR) of 51% in subjects' target lesions (25% Complete Response and 26% Partial Response);
- 69% disease control in these lesions (combined Complete, Partial and Stable Response subjects);
- 33% of subjects having an untreated bystander melanoma lesion achieved an OR in their bystander lesions while 50% achieved disease control in these lesions;
- Response of bystander lesions was highly correlated with outcome in treated target lesions, with a bystander lesion OR of 61% in subjects achieving complete or partial response in their target lesions versus 18% bystander lesion OR in subjects that did not achieve this level or response in their target lesions;
- Stage III subjects experienced a substantially higher target lesion response rate (60% OR and 79% disease control) versus Stage IV subjects (22% and 33%, respectively);
- Similar trends were noted in response metrics for bystander lesions between these two subpopulations;
- Analysis of temporal data showed that Stage III subjects also experienced significantly greater mean Progression Free Survival (PFS) of at least 9.7 months, versus 3.1 months for Stage IV subjects (median PFS for Stage III subjects was not reached during the 12-month study interval);
- Overall survival (OS) data were also presented by disease stage, with Stage III subjects achieving a mean overall survival of at least 12.6 months (median not reached during the study interval) versus 7.3 months for Stage IV subjects.
- Case studies on several subjects illustrated potential stasis or regression of untreated visceral lesions following PV-10 treatment of their cutaneous lesions, while data on long-term treatment of one study participant demonstrated successful management of the disease over a period exceeding 3 years.
Dr. Eric Wachter, PhD, Chief Technical Officer of Provectus and Study Director for the clinical trial, noted that, "These final analyses confirm previously reported trends from preliminary data. The high response rates for target and bystander lesions in Stage III subjects are particularly striking and illustrate the potential for PV-10 to benefit these challenging cases."
Dr. Agarwala, commenting on the reported data, stated, "These results further confirm the robust response that can be achieved with PV-10. This is particularly clear in Stage III patients where it is possible to inject all or virtually all of the patient's melanoma lesions. Despite the strict limits on dosing schedule in the Phase 2 protocol, many of the patients achieved excellent disease control or even complete remission. I find it quite remarkable that this included a number of subjects who experienced favorable response in their untreated skin or visceral lesions."
A copy of the poster can be found at the following link:
In addition to these phase 2 data, the company also provided further guidance on final design for its proposed Phase 3 Randomized Controlled Trial ("RCT") of PV-10 for metastatic melanoma. The study design is predicated on testing response of PV-10 in subjects most likely to derive clinical benefit from treatment of their cutaneous and subcutaneous melanoma lesions, specifically Stage III patients comparable to those investigated in the Phase 2 study. The design is anticipated to qualify as a pivotal trial under Special Protocol Assessment ("SPA") with the U.S. FDA. An SPA from the FDA is an agreement that the Phase 3 study design endpoints, statistical analyses and operational components of the planned clinical trials are acceptable to support approval of the product. Design parameters presented at ESMO include:
- Approximately 180 subjects with Stage IIIB-IIIC melanoma, as supported by the Phase 2 response data;
- Eligible subjects will have no active nodal disease (i.e., any involved nodes must have been excised prior to enrollment);
- Subjects will be randomized 2 : 1 to PV-10 or systemic chemotherapy (dacarbazine or temozolomide);
- In the PV-10 arm all cutaneous and subcutaneous lesions will be treated within the first two weeks, with additional treatment allowed every 14 days as necessary to achieve disease control;
- In the chemotherapy arm standard 28 day dosing schedules will be used;
- Clinical response will be assessed every 4 weeks, with full response assessment every 12 weeks, during the study interval;
- Progression Free Survival (PFS) will serve as the primary endpoint, with progression defined to include increased tumor burden, advent of active nodal disease, onset of distant metastasis and symptomatic deterioration based on validated instruments.
The study duration is estimated to be approximately 30 months, with commencement expected in late 2012 or early 2013 following completion of review for SPA.
Dr. Wachter, commenting on the Phase 3 study design, noted, "This study is designed to demonstrate delay or avoidance of progression of melanoma from a locoregional disease to a life-threatening systemic stage. The proposed study population experienced excellent response to PV-10 in the Phase 2 study, and this bodes well for the planned Phase 3 study, where subjects will receive treatment on an even more aggressive schedule than that allowed in Phase 2. Since our last meeting with FDA in late 2011, we have carefully studied the outcome of different sub-populations of subjects in the Phase 2 study, reviewed the criteria to be used for unambiguous assessment of response, and fostered relationships with key parties that will provide support in execution of the Phase 3 study. We look forward to formal review of the resultant protocol and supportive programmatic elements with FDA under the SPA process."
Craig Dees, Ph.D, CEO of Provectus said, "The protocol design presented at ESMO reflects guidance we’ve received during discussions with the FDA and the Australian Therapeutic Goods Association ("TGA") about our proposed Phase 3 trial for metastatic melanoma. We have also completed detailed operational planning, something which the FDA now frequently expects as part of the SPA package and a critical step to assure that the study runs smoothly. The SPA is probably the most important milestone Provectus will have achieved in our efforts to gain approval for PV-10. We expect to keep shareholders updated on our progress as we continue to advance the development of PV-10."
The European Society for Medical Oncology (ESMO) is the leading European professional organization, committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care. Since its founding in 1975 as a non-profit organization, ESMO's mission has been to advance cancer care and cure. It achieves this through fostering and disseminating good science that leads to better medicine and determines best practice. In this way ESMO fulfills its goal to support oncology professionals in providing people with cancer the most effective treatments available and the high-quality care they deserve.
About Provectus Pharmaceuticals, Inc.
Provectus Pharmaceuticals specializes in developing oncology and dermatology therapies. Its novel oncology drug PV-10 is designed to selectively target and destroy cancer cells without harming surrounding healthy tissue, significantly reducing potential for systemic side effects. Its oncology focus is on melanoma, breast cancer and cancers of the liver. The Company has received orphan drug designations from the FDA for its melanoma and hepatocellular carcinoma indications. Its dermatological drug PH-10 also targets abnormal or diseased cells, with the current focus on psoriasis and atopic dermatitis. Provectus has recently completed Phase 2 trials of PV-10 as a therapy for metastatic melanoma, and of PH-10 as a topical treatment for atopic dermatitis and psoriasis. Information about these and the Company's other clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus please visit the Company's website at www.pvct.com or contact Porter, LeVay & Rose, Inc.
FORWARD-LOOKING STATEMENTS: The forward-looking statements contained herein are subject to certain risks and uncertainties that could cause actual results to differ materially from those reflected in the forward-looking statements. Readers are cautioned not to place undue reliance on these forward-looking statements, which reflect management's analysis only as of the date hereof. The company undertakes no obligation to publicly revise these forward-looking statements to reflect events or circumstances that arise after the date thereof.
Provectus Pharmaceuticals, Inc.
Peter R. Culpepper, CFO, COO
Phone: 866-594-5999 #30
Porter, LeVay & Rose, Inc.
Marlon Nurse, DM, SVP – Investor Relations
Bill Gordon, SVP – Media Relations
Source: Provectus Pharmaceuticals, Inc.