October 4, 2014

“We should see a difference very quickly between PV-10 and chemotherapy responses”

Medical writer Walter Alexander, who has written several articles and stories about Rose Bengal, PV-10 and Provectus (such as here, here and here), penned another article, Cutaneous, Locoregional Melanomas Show High, Rapid Responses to Injection With Rose-Bengal Solution: Presented at ESMO Congress (October 2, 2014). I found the following noteworthy and repeating.
Intralesional injections of PV-10 accumulate rapidly in tumour lysosomes, causing lysosomal rupture within 30 to 60 minutes and subsequent tumour-cell rupture, noted lead investigator Sanjiv Agarwala, MD, St. Luke’s University Hospital & Health Network, Bethlehem, Pennsylvania, speaking here at a poster session on September 28. Research has shown subsequent tumour-specific T-cell responses to occur within 7 days, he added. {Underlined emphasis is mine. 
 I added the illustration below from Provectus' ESMO 2014 poster for effect.
Click to enlarge.
In the All Lesions Treated group, 121 complete responses were observed after 1 injection, 84 complete responses after 2 injections, 22 complete responses after 3 injections, and 5 complete responses after 4 injections. 
I added the illustration below from Provectus' ESMO 2014 poster for effect. Note the drug's 74% complete response, and that PV-10 was last allowed at week 16. In Amgen's talimogene laherparepvec's ("T-Vec's") pre-specified retrospective analysis of tumor-level responses from its pivotal Phase 3 trial, T-Vec achieved 47% complete response (almost 4000 lesions were included in the analysis).
Click to enlarge.
Progression-free survival in the All Lesions Treated group was 9.8 months. In the uninjected Bystander Lesion group from the original trial, progression-free survival was 8.9 months.
I added the illustration below from Provectus' ESMO 2014 poster for effect. Note PFS calculations are consistent with RECIST 1.1.}
Click to enlarge.
“We should see a difference very quickly between PV-10 and chemotherapy responses,” Dr. Agarwala added.
From my news item How much is enough, and when? (September 16, 2014): In the upcoming Phase 3 trial Provectus will measure PFS as the trial's primary endpoint, utilize RECIST 1.1 to measure it, and inject patients every two weeks until CR or PD is achieved (i.e., the duration of the treatment interval will be until one of the two outcomes is achieved). It then could be reasonable to project a PV-10 arm PFS of 12 months for a 12-month observance period, 9 months for a 9-month period, 6 months for a 6-month period or 3 months for 3-month period -- where, at best, the PFS and its confidence interval are the same line, or, at worst, the CI is a narrow band around the PV-10 PFS figure, which itself would be a horizontal line at 1.0 or 100%. Thus, patients with all of their disease treated by PV-10 would never progress, while patients in the control arm (those treated with DTIC or TMZ) would suffer progression as historically demonstrated through prior use and over many previous clinical trials.
Click to enlarge.
Approximately 1 third of patients with melanoma are diagnosed with predominantly locoregional disease.
From my news item PV-10 is tantamount to surgery? (September 5, 2014): The silent masses who make up the bulk of patients with melanoma (and the much larger addressable market), however, remain without effective options:
Click to enlarge.
SEER Stat Fact Sheets: Melanoma of the Skin, National Cancer Institute

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