The primary business strategy has been, from the start, to show proof of concept for as many oncology indications as possible before partnering PV-10 in the endgame scenario:
- Metastatic melanoma: Phase 2 completed (safety, dosage and efficacy well documented). Waiting on the approval of the Phase 3 design.
- Breast cancer: Phase 1 completed (safety achieved. dosage understood. efficacy noted).
- Liver cancer: Phase 1 completed (safety achieved. dosage understood. efficacy documented). Currently completing Phase 2/Phase 3 design.
- Pancreatic cancer: Contemplating a Phase 1 trial.
- Other solid tumors: Colorectal (liver Phase 1) Squamous cell carcinoma (Compassionate care program), Scalp sarcomas (CC)
The lead clinical trial has been for metastatic melanoma. At ASCO 2011, despite the fanfare for ipilimumab and vemurafenib, BRAF inhibitors and CTLA-4 antibodies still only are very marginal improvements in treating very late stage melanoma. In addition, the patient populations represented by these studies highlighted the lack of attention paid to patients most obviously appropriate for PV-10. In October's PR related to the 3rd EOP2 meeting with the FDA, "...melanoma, which is a rapidly evolving therapeutic area" means the FDA recognizes that the approvals of ipilimumab and vemurafenib address only part of the melanoma patient population and that other areas (i.e., the bulk of recurrent melanoma) still are unmet needs.
The mostly has been treating patients in Stage IIIb, IIIc and IV M1a, but also some IV M1b and IV M1c. Tactically, the company can successfully treat all of these disease stages. Most metastatic melanoma, however, is in Stage IIIb-IV M1a. Very late stage IV M1b and IV M1c is visceral metastatic disease. Strategically, Provectus' target label for approval is Stage IIIb-IV M1a because this is non-visceral metastatic disease.
Management is deliberately and methodically proceeding towards a non-visceral disease claim with the FDA in order to get it approved as quickly and as inexpensively (balance sheet item: accumulated deficit) as possible.
The primary regulatory approval path had been to seek accelerated approval through a combination of the MM Phase 1 data and data from the first cohort of 40 patients from the MM Phase 2 trial. The secondary path was a well laid out RCT Phase 3 trial. See the illustration below.
Unfortunately for patients, shareholders and management, the long history of safety of rose bengal, the stunning efficacy of PV-10 in the Phase 1 trial, and the reproducibility of results [from an interim look-back] in the Phase 2 trial, together with a change in regulatory perspective, were insufficient to sway the FDA to give PV-10 accelerated approval. With the benefit of hindsight and a suitable arms-length partner like Moffitt, the results of the two completed immuno-studies would have tipped the scale in management's favor. The cost? Likely 12 to 18 months.
The company now finds itself following its secondary path, which already was planned but now must be traversed.