Management noted in Wednesday's 8-K filing they "...took the opportunity to provide input into the documentation of meeting minute notes." I believe this input refers to data and statistical analysis related to the topic of tumor destruction (and more broadly locoregional disease control) upon injection of PV-10 into patient lesions. Recall Provectus' European Cancer Congress ("ECC") 2013 poster presentation (poster here, press release here). While the trial was a typical or traditional patient study, Provectus also collected (categorized) data on a per lesion basis. One might almost think of the trial as a "lesion study," where although N was the number of patients or subjects, n was the number of lesions. I believe about or more than a 1,000 lesions were treated and/or observed, of which 491 were treated as target lesions. Among these 491 lesions, 53% achieved complete response ("CR"), 5% partial response ("PR") and 12% stable disease ("SD"). 70% locoregional disease control (CR+PR+SD).
Pieces of Craig's two quotes in the ECC 2013 press release are quite relevant (see my bold underlined emphasis below):
- "The researchers concluded that PV-10 has a unique immuno-chemoablative profile that offers significant potential due to several important attributes. First, its safety and efficacy compare favorably with existing and emerging therapies. Second, its safety profile makes it an attractive candidate as a combination strategy for treatment of advanced disease. And finally, it provides a powerful combination of rapid reduction of tumor burden with induction of tumor-specific immune response that can achieve rapid disease control in refractory patients with locally advanced melanoma."
- "Melanoma patients and their caregivers experience profound discouragement upon recurrence of the serious skin manifestations of this disease. The investigators on this study describe the effect of PV-10 as "rapid, durable response" but as the photographs have documented, many of the PV-10 treated tumors almost appear to have never been present. PV-10 was only injected intermittently, when tumors were present during the first 16 weeks of the study, in stark contrast to typical clinical studies where treatment is given until either resistance is engendered or patients experience unacceptable toxicity. We are gratified that response to PV-10 was demonstrated consistently across all study centers, with minimal intervention in patients refractory to multiple prior treatments. PV-10’s unique mechanism of action, alone or in combination with existing or emerging therapy, has the potential to shift the paradigm in oncology, where an intermittent intervention can dramatically reduce disease burden and may prod the immune system into preventing or arresting the formation of life threatening metastases."
Eric, whose responsibilities at Provectus include biostatistics, may have worked with the FDA to provide or isolate data from the company's metastatic melanoma Phase 2 trial to support statistical significance or relevance of locoregional disease control at a lesion level (not merely at a patient level). p-values, for example, previously have been provided by the company for N (i.e., subjects) in past presentations. p-values, which I use for illustrative purposes (I don't know what specific statistical parameter(s) the Agency would require), for lesions have not. If the FDA recognized new endpoints (tumor- or symptom-based) were appropriate and necessary for PV-10, Eric, following the December 16th meeting, could have recasted already collected and locked data as such for the Agency to consider. If this work indeed was the "input" Provectus took the opportunity to provide, and if accepted by the FDA, then it's not unreasonable for an approval pathway potentially to follow.
Now consider the changes to the website presentation, which was updated today. It seems to me management is saying exactly that: an approval pathway, currently being collaboratively developed with the Agency, should follow.
|Click to enlarge the figure.|