What PV-10 is doing is “unprecedented”

"...under investigation as a non-surgical option

to induce tumor regression of cutaneous neoplasms."

(Moffitt AACR 2014 abstract)

Provectus issued press release Induction of Systemic Immunity Following Treatment of Tumors with PV-10 Reported by Moffitt Cancer Center Researchers at American Association for Cancer Research Annual Meeting today, following up on Moffitt's AACR abstract Induction of anti-melanoma immunity after intralesional ablative therapy.

No poster was provided in the PR. According to management, it will be available after the American Society of Clinical Oncology ("ASCO") meeting that runs from May 30th to June 3rd. Interestingly and previously, the company has PRed Moffitt's Society of Surgical Oncology 2012 and AACR 2013 posters once the conferences ended (AACR 2014 ends June 9th).

My takeaways and questions include:

1. Inject PV-10 and the tumor goes away, and does not come back

• Phase 1, 20 patients, limited injection protocol, 75% locoregional disease control
• 20% (CR) + 20% (PR) + 35% (SD)
• Phase 2, 28-patient subset used for BTD application, all disease treated, 88% locoregional disease control
• Adjusting for the 2 non-evaluable patients, 54% (CR) + 23% (PR) + 12% (SD)
• Moffitt, August 22, 2013: Single Injection May Revolutionize Melanoma Treatment, Moffitt Study Shows
• Craig, March 24, 2014 PR: "...if you inject PV-10 into melanoma tumors, the tumors go away." 
• Moffitt feasibility study, 8 patients, AACR 2014: "...biopsies of patient tumors collected just 7-14 days after PV-10 injection no longer contained viable tumor tissue."

2. PV-10 injection [effectively] is equivalent to surgery (i.e., a non-surgical treatment option)

When melanoma is identified in Stages 0-III melanoma, excision of a sort (e.g., small, wide, deep, etc.) typically is the primary, initial or main treatment. More specifically, surgery is a therapeutic and diagnostic biopsy: remove the diseased tissue and take samples around the surgical margins to ensure the surgeon has removed the cancer, all within a few days.

At AAC 2014 Moffitt found in and around the injected lesions:

• No viable tumor tissue,
• Healthy tissue around the margins, and
• No tumor-infiltrating lymphocytes because the injected tumor went away faster (probably measured in a few days like three) than the planned for 7-14 follow-up period.

A cutaneous neoplasm is a cancerous lesion on the skin. A skin cancer equals a skin neoplasm.

Given this, how is PV-10 injection not equivalent to or better than surgery? PV-10 injection accomplishes the same goals as a diagnostic and therapeutic biopsy, but spares the tissue.

Moffitt's study investigated whether PV-10 was a non-surgical option. Is it not now?

3. The FDA, and a bridging study post-approval

Moffitt's data very likely should have been provided to the FDA. Moffitt's documentation of PV-10 effect on injected lesions in their 8-patient study clearly builds on Provectus' metastatic melanoma Phase 2 trial 28-patient subset that had all disease treated. "...[I]f you inject PV-10 into melanoma tumors, the tumors go away."

Given this, how could the bridging study not be done post-approval?

4. We know more, and less

AACR 2014 revealed Moffitt knows more about the whats of PV-10 injection on treated and untreated melanoma lesions. It also revealed they still don't fully know the whys. But what happened to the patients in Moffitt's feasibility study? The study protocol required the patients to be [essentially] experimented upon within a few days. If PV-10 worked so well requiring Moffitt to change their study design to re-examine injection sites much sooner than 7-14 days, were other lesions in these metastatic melanoma (Stage IV) patients subsequently and/or all treated too, following the initial study of or experimentation on intended to treat and not intended to treat lesions?

The AACR 2014 poster is effectively embargoed until ASCO 2014 (and thus preventing us from seeing further detail of the study, results and patients). I can only wonder if (speculate whether) Moffitt's ASCO abstract's title Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions means patient follow-up will be discussed at ASCO.

5. Melanoma

The PR noted Provectus' breakthrough therapy designation ("BTD") submission again: Provectus has applied to the FDA for breakthrough therapy designation of PV-10 for the treatment of melanoma based on a 7 center international single-arm trial." {Underlined emphasis is mine above}.

As I wrote under the blog's News tab for "Trial design endpoints should be tailored to the strength of your drug" (April 5, 2014), PV-10 is being considered for approval for local (non-metastatic) disease. Local (including local regional or loco-regional) disease represents more than 95% of the addressable melanoma market (see, for example, Recurrent Loco-Regionally Advanced Melanoma Market > Metastatic Melanoma Market (January 25, 2014) below).

I believe management is making a point in today's PR about the implications of the resultant outcome from a BTD award.