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Biotech / Medical : Provectus Pharmaceuticals Inc. -- Ignore unavailable to you. Want to Upgrade?

To: LT2011 who wrote (11963)	5/22/2013 3:56:08 PM
From: NTTG	1 Recommendation Read Replies (2) \| Respond to of 13111

Yep. There has been confusion by some over the years about the meaning of a CR/PR dataset that comes from measurement of 'injected lesions' and the CR/PR for a whole patient (overall survival, progression free survival, time to progression, etc). The company position is that the presumed immune activation will create a 'bystander' effect that is as effective in slowing/halting MM as a clinical response to systemic therapy. That hypothesis will be tested for the first time in the PIII trial design, where progression free patient survival will be the primary end point. I am not sure why Boomer keeps talking about local/regional control? The company is hoping they will get a dosing regimen that maximizes local regional control, thereby improving their chances of a PFS effect, but the jury is still out on where the FDA will draw the dose line. If the company fails to achieve the systemic PFS HR of < 0.545 compared to DTIC or TMZ, then PV-10 will not get to market on this round, and the local control story is mute. It is likely that the company will be allowed to measure bystander lesions as a secondary endpoint (like they did in the PII study), but secondary endpoints are rarely used to make a claim in the final label, particularly when there is so little data to establish causality. In a way, the point is mute...in order for PV-10 to reach the PFS HR goal in non-progressing stage 3 patients, some type of clinical impact on distant lesions will have to happen in order to 'match' the effect of a systemic therapy. If that goal is attained, the 'how' question is less important.....unless..... the company wants to make a specific claim in their label about the bystander effect. In that case the situation becomes more like a chicken - egg discussion for PVCT... Measuring the bystander lesion response without a corollary biomarker for immune activation will not be sufficient to allow the company to claim an immune mediated bystander effect in their label. Committing to a PIII trial design and measuring the wrong (or a non-informative) biomarker has the same problem. The only way to get a 'bystander effect' claim in the label is to show the lesion data and evidence that an mechanistically related immune activation step has occurred....but which biomarker, and when in the course of therapy? Hence the attention to MOA studies in mice and humans recently, and likely the reason for increasing attention to 'combination Tx' that will boost the immune response if they are not allowed to inject every visible lesion....just a hunch. I think Argarwala is informing readers that PVCT will not be able to figure this out ahead of the PIII.