May 17, 2013

Big Pharma: "We are pretty good at shrinking tumors, but not good at getting rid of them."

Houston, Big Pharma has a problem. Lots of drug candidates, and lots of shrinking. But Big Pharma still cannot get rid of cancer tumors.

A blog reader forwarded me Dr. Sally Church PhD's post on ASCO 2013 highlights of PD-1 and PDL-1 immunotherapy, which are capturing media attention. Thank you. Her key points include (a) too much focus on overall respons rate (ORR), (b) ORR is a measure of disease control, not disease cure or a measure of response durability, (c) being sure to compare apples to apples when examining these ASCO abstract results, and (d) ORR not being an ideal endpoint, but rather how long do patients live, do they feel better and do they have a better quality of life.

ORR = CR + PR. Overall response rate equals complete response plus partial response. From RECIST criteria, CR (complete response) = disappearance of all target lesions, and PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions.

PV-10's clinical value proposition is very simple: Very safe. Very efficacious (effective). Very useful (on many different solid tumor cancers).

Key, within this value proposition, are how high CR is -- the elimination of tumors, not merely the shrinkage of them -- and the durability of the response to PV-10 -- one the tumors are eliminated, they don't come back. Thus, PV-10's more nuanced value proposition: Permanent elimination.

Only shrinking tumors, but not fully eliminating them, has the effect of allowing resistance to build up to drug treatment. Harnessing the immune system to turn tumor heterogeneity on its head is facilitated by tumor elimination.

Other historical therapies -- from the previous standard of care of DTIC to anti-CTLA-4 agents like treme and ipi to intralesional therapies immunotherapies like Allovectin-7 and OncoVex (T-Vec or talimogene laherparepvec) to emerging immunotherapies like anti-PD-1 and anti-PDL-1 agents -- do not have the complete response of tumors that PV-10 generates.

In the Phase 2 trial, there was an 80% treatment success rate of individual lesions with an associated complete response ("CR") of more than 50%. Think of a set of data comprising all lesions treated, irrespective of patient. Success was achieved in 80% of these datapoints. 80% success was achieved despite limited treatment (i.e., 1 initial injection and up to 3 additional injections), physician error while injecting lesions (i.e., some lesions were improperly injected), patients and their lesions left the trial, and patients with compromised immune systems and ravaged bodies from failed prior treatments had their lesions injected.

Final results of patients included:

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