Overall Survival

Overall survival (OS) is the so-called gold standard for trial endpoint. Several years back, the FDA issued an oncology guidance document stating that overall survival is usually preferred, but progression free survival (PFS) may be appropriate in some cases (link). Other gold standards include improving “quality of life” measures, reducing toxicity of treatment, and reducing the cost of treatment.

The company has underreported OS; there are snippets of information about OS from the MM Phase 1 trial and the first cohort of the MM Phase 2 trial. Full MM Phase 2 trial data related to OS, however, only will be available when the peer-reviewed article on this trial is published in the globally recognized periodical management says may come out later this year or early next year.

Quite some time back, I wanted to compare what OS data was available for PV-10 (see here and here) to other studies. Korn et al. (2008) performed a meta-analysis of 42 MM phase 2 metastatic melanoma studies (70 arms) that included 2,100 patients.

I did compare. Fully understanding the caveats of comparing trials and comparisons themselves -- comparisons provide useful information, but of course one does not digest them in a vacuum -- I gained robust knowledge.

In Figure 3 of their paper (below), the authors present "event rates for each trial arm versus the sample size in the trial arm: (A) overall survival (OS) rates at 1 year, (B) progression-free survival (PFS) rates at 6 months. The solid lines are 95% confidence bounds. The dotted line is the overall 1-year survival rate (25%) or the overall 6-month PFS rate (15%). (A small number of plotted points have been slightly jittered to avoid complete overlap.)‏"

I added the OS data available for the first cohort of 40 patients of PV-10's MM Phase 2 trial. Note where PV-10 sits on the two graphs for 1-year OS and 6-month PFS.

As a comparison, a couple of years ago, OncoVEX(GM-CSF)'s 50-patient MM Phase 2 trial achieved a 0.58 (58%) 1-year survival figure and compared (positioned) OncoVEX on Korn et al.'s graph.

Amgen acquired BioVex, the maker of OncoVEX, announcing the signing of the deal in January 2011, for an upfront payment of $425 million upfront and [likely up to] $575 million in additional development and sales milestones. At the time, Michael Yee, an analyst with RBC Capital markets, told Bloomberg: "It's a call option on a late-stage, potential blockbuster drug for Amgen." BioVex commenced OncoVEX's pivotal MM Phase 3 trial in April 2009.

Now, it is quite possible that, when the full Phase 2 data is published, the orange dots of PV-10 move upward (better 1-year OS, better 6-month PFS) and to the right (more patients; i.e., n=80). The conservative nature of the principal investigators and, thus, their initial data analyses and presentations could differ (be lower) from the results generated by a suitably conducted, appropriate and extensive data validation process, one that I imagine would or will have been undertaken before the Phase 2 data would have been or will be released for publication.

BioVex heralded OncoVEX's position on Korn et al.'s graph by noting that no study fell outside the 95% confidence intervals denoted by the solid lines.

What would be your perspective of Provectus and PV-10, given the positioning of the orange dots for the first cohort and the entire trial?

• A higher 1-year OS than OncoVEX (upward), and
• A larger trial-arm sample size than OncoVEX (to the right).