Blog Reader Question

Do you feel like the negative opinions on Oncovax and Vical has been a factor in keeping Provectus's stock price down? What sort of primary endpoint is Provectus aiming for in its phase III trial?

I think there are two ways to look at drugs like OncoVEX (Amgen), Allovectin (Vical) and PV-10.

First, as treatment options for local disease. Intralesional therapies are beginning to gain acceptance as a potential tool in an oncologist's tool kit to treat his or her patients based on the successes such therapies have demonstrated in Phase 2 trials to date. I found a nice illustrative definition of intralesional therapy: "Intralesional therapy implies injecting a drug directly into the skin lesion for faster action & better results. The concept of intralesional injection is to let the drug pass the barrier zone and establish a sub-epidermal depot thus allowing a higher concentration of the drug to act at the site of the disease."

Second, as treatment options for systemic disease. This is where their inclusion in or association with the "category" of cancer immunotherapy comes into play. The HemOnc Today conference highlighted the ongoing discussions practitioners are having in regards to the suitable role for intralesional therapy in treating local and systemic disease. Their harnessing of the immune system to treat systemic disease allows these drugs to play a more prominent role in the physician's tool kit.

Negative opinions of the prospects of late-stage trials of two of the more well-known intralesional therapies (OncoVEX and Allovectin) relate to the likely (or in their cases, unlikely) success of their respective trials. But such opinions derive from expectations of where such drugs fit into a physician's treatment decision tree, which derives from expectations of the size of the addressable market for which these drugs can be prescribed, which derives from expectations of the valuation the drugs and, thus, the companies can gin up in the public markets (or from prospective acquirers if the companies were private). A labeling of only being able to treat local disease limits the size and scope of the financial opportunity for these drugs and the companies that produce them.

As a result, it is possible that negative opinions of OncoVEX and Allovectin-7 might be weighing on Provectus' share price, but I doubt the weight is meaningful. Rather, the relative nascency of cancer immunotherapy creates skepticism that likely weighs much more. Further, PV-10 and Provectus does not yet have the market awareness that a Vical or, let alone, an Amgen possesses. It is one thing to have the light of investor awareness shone on you, in response to which you wilt or flourish. Is another simply to have the light shone on you. More awareness on PV-10 and the company will begin to take care of the share price.

The primary endpoint of Provectus' pivotal MM Phase 3 trial likely should be a modified progression free survival (PFS), which is a time-to-event endpoint, like overall survival (OS). PFS also is referred to as disease free survival (DFS).

Thus, the "modified" descriptor means Provectus only is concerned with the spread of the disease beyond the local area. Recall that the label management seeks for PV-10 is treatment of local disease. If the patient had systemic or visceral disease by definition, then the endpoint would be PFS or, more likely, OS. Since the patients management proposes to treat in the company's Phase 3 have local disease, Provectus only is measuring the spread (or mostly lack of spread in PV-10's case) of that disease. Therefore, the disease of this patient population is by definition not systemic and PFS is modified in the sense that it only applies to the local disease.