For all intents and purposes, it feels like Provectus finally submitted the company’s application for breakthrough therapy designation (“BTD”) for PV-10 and lead indication metastatic melanoma (“MM”). Exactly when management hears from the FDA (e.g., 45 days, 60 days, less) is anybody's guess, but perhaps the principals (since Eric and his regulatory affairs team of consultants, all of whom have been working collaboratively and regularly with the Agency according to the company, have direct contact with and visibility to FDA officials).
There is little doubt the company's primary focus, and particularly that of Eric, since, say, around October's ESMO 2012 has been to gain regulatory clarity for PV-10 and MM. With Eric shifting regulatory affairs resources to PH-10 (toxicity and other work appears to have been completed by Rockefeller University) and focusing on PV-10's expanded Phase 1 liver trial (he may travel to China in September, along with Peter, to open a site in Shanghai), one has to presume the BTD application was sent to the FDA so that he might focus his attention on other critical matters and items.
By most accounts, the company began the process (e.g., preparing, collating, writing, etc.) in late-2012 or early-2013. By some accounts, the FDA asked management to apply for BTD in early 2013. If, as many suspect, the application recently was turned in (e.g., around the end of July or the beginning of August), for what was the time (i.e., 4-6 months) taken? Excavating this kind of information isn’t about explanations and excuses. I think it goes to the heart of management’s process and strategy, and does provide some revealing information about the timing of regulatory clarity.
There seems to be two facets of Provectus’ approach. First, answer the FDA’s questions regarding local agent PV-10 and deliver proof of its systemic properties and benefits (safety has been a given for quite some time). Second, prepare, in parallel, efforts should the drug be released for use or when the pivotal Phase 3 trial is undertaken.
In answering to and working with the FDA, it seems Moffitt Cancer Center’s PLoS-published paper, Intralesional Injection of Rose Bengal Induces a Systemic Tumor-Specific Immune Response in Murine Models of Melanoma and Breast Cancer, was critical, with Provectus wanting to wait until the paper either was accepted (end of May) or published (mid-July) before attaching it to the BTD application. The paper of course followed Moffitt’s poster presentation at early-April's AACR 2013 (the paper, however, was submitted at the end of March, prior to the conference itself). The paper, which contained much more information than the poster, seemed to mark the end of substantive questions the FDA had about systemic proof and benefit, very likely paving the way for the application’s submission and the Agency’s decision. There may have been other FDA information requests of less import that had to be complied with, but it strikes me most of the heavy lifting, understanding wise, was completed with the publishing of this portion of Moffitt’s pre-clinical work.
In preparing for the Agency’s decision, however, management prepared for several eventualities, from running a pivotal Phase 3 trial under a special protocol assessment (“SPA”) agreed to with the FDA, to a modified, truncated Phase 3 trial via BTD, to approval of one sort (accelerated approval) or another (outright approval).
Such preparation involved, among other things for example, prepping the CMC section of the NDA filing to approve PV-10. This included, for example, conducting several production runs with the new synthesis process that only received a key patent allowance in June. These production runs subsequently were run, and information from them passed on to the FDA. Whether a Phase 3 trial is run, or whether the drug is approved, the production runs were necessary for the process.
The application clearly is in (and if not, will be very shortly, potentially providing clarity in October, rather than by the end of September) and we await the revelation of the FDA's decision.