It's a wonder any new drug ever makes it to market. The excerpts below reveal that the FDA is an incompetent bureaucracy at best or a bureaucracy tainted by outside influences at worst. It is disturbing that the FDA is going to such lengths to STIFLE new drug development.
The FDA was WRONG in EVERY assumption they made in the three meetings with Provectus described below. In this case the FDA has singlehandedly added 4 years to the approval process for this drug. How many people have died and will die because of this FDA generated clusterfu*k? And yet they still seek to delay bringing this drug to market. UNBELIEVEABLE!
From the conference call...
Why did it take four years from the end of phase two study to arrive at this point?
I think it is good to start back in May of 2010 when the last patient completed the phase two study. Shortly before that point, we held our first type A meeting with the Agency. That was in April of that year when we had interim data from the first 40 patients in the study. And what was interesting to me as the study progressed, we had interim analyses scheduled at N equals 20 patients, N equals 40 patients, and then a final analysis when the total of 80 intent to treat patients, or ITT population was enrolled. And by the time we got to N equals 40 patients, the numbers were looking better than what we had seen in phase one, which we expected based on a more aggressive treatment of the patients, despite the fact that we had, uh, a larger number of stage four patients in the patient population. I'll comment that as we finally matured the data to N equals 80 patients, the response metrics remained roughly the same over time. And at this time in April of 2010, the melanoma landscape was beginning to change very rapidly with ipilimumab and vemurafenib approvals approaching on the horizon. This meeting established that what we proposed at the time for phase three study in patients with a patient population and end point similar to studies underway at that time under special protocol assessment for two other investigational intralesional therapies for melanoma would not be appropriate going forward. The Agency told us that they did not like our proposed patient population nor our end points, and also cast tremendous amount of doubt on the relevance of the drug in melanoma, a disease that they noted was systemically malignant and would be difficult to treat with a local therapy. We matured the data from the phase two study further and held a second meeting finally in March of 2011 after completing our initial analysis of data from the full 80 patient data set from the phase two study. We went into the meeting with proposed end points and patient population modified based on guidance from the first meeting. That study design was proposed to evaluate response in patients with, uh, Stage IIIB to IVM1A disease. These are patients with cutaneous or nodal disease, uh, and where all disease would be accessible by intralesional injection. In addition, we tightened the definition of dermal response that we had proposed, uh, in that first meeting in light of the Agency's advice. At this meeting, the Agency made it clear that a time to event end point would be required and expressed concern about our proposed modifications to RECIST that we felt were relevant to treatment of local recurrence. We met with our advisors further and finally scheduled and held a third type B meeting in October of 2011. At that meeting, we proposed modified end points in the patient population, once again based on prior guidance. This study was proposed to evaluate response in patients with cutaneous or subcutaneous recurrent or metastatic melanoma. Okay. That's a lot to digest, the cutaneous or subcutaneous recurrent metastatic melanoma that had no active nodal or visceral disease. These were patients, for example, with a history of nodal disease that had undergone nodal resection and would be candidates because their nodal disease had been surgically removed. They had no active nodal disease, similarly a case for patients that might have had limited lung mets, for example, that had been successfully treated somehow surgically, radiation, or some other therapy. Progression free survival versus DTIC was proposed for our RCT. We proposed a time to event end point in a randomized controlled trial. The Agency at that point expressed continued concern about enrolling patients with any history of visceral disease based on the concern I mentioned earlier, that there was inadequate support for use of PV-10 intralesionally in patients with systemic disease, so local therapy for patients with systemic disease. They also expressed concern about our proposed effect size, which we were willing to address. At the conclusion of the meeting, we agreed to develop a revised RCT design in patients with no history of visceral disease and no active nodal disease, and to submit this for SPA. ... Finally, by October of 2013, we had become sufficiently frustrated by the difficulties posed by design of a study based on the third type [B] meeting and the discussions leading up to that third type [B] meeting, and also encouraged with the emerging immunologic mechanism data, such that we requested an additional meeting with the Agency in the fall of 2013. ...
AI
