Generating Clinical Data

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"We firmly believe that Phase 3 testing should not be started unless you can adequately predict the outcome. It's critical to understand what the drug is doing, which patients are most likely to benefit, what other options those patients have, and which endpoints would be most convincing for government agencies to approved the labelled indication for the drug."

— Dr. Eric Wachter, PhD, Chief Technology Officer, Provectus Biopharmaceuticals, June 19, 2014 investor conference call 

"With an agent that is so promising in laboratory, it’s incumbent on us, the management of Provectus, to ensure that clinical trials are designed and executed to understand what this means in patients with melanoma and other cancers. 

As Chief Technology Officer, it’s my responsibility to carefully design the right studies to safely collect not just data, but the most appropriate data needed to understand any drug effect and detect any signal, hopefully, improvement in cancer patients. Each of our clinical studies: present, past and future, is designed with that purpose in mind." 

— Eric Wachter, November 5, 2015 3Q15 business update conference call

Evolving thoughts about Provectus' trials and "tribulations" in pursuit of generating more clinical data, randomized and otherwise.

Official title: PV-10 Intralesional Injection vs Systemic Chemotherapy for Treatment of Locally Advanced Cutaneous Melanoma Without Distant Metastases

• Crux: The initial pathway of approval for PV-10

• Hypotheses:

• Complete response of injected tumors is tantamount to elimination of disease symptoms

• PV-10 can forestall or prevent the spread of the disease from Stage III to Stage IV if all of it is treated

• Ideology: Focus on earlier treatment of cancer patients (i.e., < Stage III) (this will be a longer fight in order to change long-held beliefs and attitudes long-term)

• Comparison: PV-10 vs. dacarbazine (or temozolomide) (for approval as a single agent therapy for use in patients with Stage III disease)

• Process speculation:

• Demonstrate statistically significant progression-free survival (PFS) (primary endpoint) curve separation

• Collect qualitative and quantitative patient-reported outcome (PRO) data

• Undertake an interim data readout

• Submit for accelerated approval consideration

• Complete the Phase 3 trial as a post-marketing commitment in order to collect overall survival (OS) (secondary endpoint) data

• Question: The larger the difference between the treatment drug's treatment effect and the control drug's treatment effect, the smaller the number of patients required to achieve statistically significant curve clinical endpoint separation. If all control arm patients progress and no treatment arm patients progress -- how many patients are required?

Official title: A Phase 1b/2 Study of PV-10 Intralesional Injection in Combination With Systemic Immune Checkpoint Inhibition for Treatment of Metastatic Melanoma

• Crux: That PV-10 can work in combination with another drug or drug compound, proving orthogonality from both safety and efficacy perspectives

• Hypothesis: PV-10, together with a checkpoint inhibitor, can benefit patients (Stage IV) with disease inaccessible to PV-10 injection

• Ideology: Demonstrate a PV-10 solution for end-stage patients

• Comparison: Standard of care (SOC) (pembrolizumab) vs. SOC + PV-10 (for approval as a single agent for use in patients with Stage IV disease)

• Process speculation (partial process):

• Demonstrate safety and tolerability (i.e., frequency, duration, severity and attribution of adverse events and toxicities)

• Demonstrate efficacy via PFS (primary endpoint) and objective response rate (secondary endpoint)

• Populate electronic data room with preliminary initial data, and present some of this data

• Question: How good could this data be? It has to be in order to rise notably above the noise of the many combination therapies trials already being run.

The liver cancer study into which the current expanded Phase 1 study, which evolved from its Phase 1 study, will evolve

• Official title: ?

• Hypothesis: PV-10 can benefit patients with loco-regional hepatocellular carcinoma (HCC)

• Ideology: Demonstrate multi-indication viability

• Comparison:

• Asia (China, Singapore, Taiwan, South Korea): SOC (local ablation technology) vs. SOC + PV-10 (for approval as a single agent for use in patients with loco-regional HCC)

• U.S. & Western Europe: SOC (sorafenib) vs. SOC + PV-10 (for approval as a single agent for use in patients with loco-regional HCC)

• Process speculation (partial process):

• File and have accepted by the FDA a Phase 2 randomized control trial of sorafenib vs. sorafenib + PV-10

• File and have accepted by the CFDA (and other regional regulatory authorities) a Phase 1b of local ablation technology + PV-10