On Tuesday, April 12, 2011 the FDA Oncology Advisory Committee will discuss Pfizer‘s application for the use of SUTENT in patients with unresectable pancreatic neuroendocrine tumors. SUTENT has 2 approved indications, including use in patients with advanced renal cell carcinoma.
Based on the issues raised in the FDA Briefing Document, Pfizer might want to spend some time explaining their regulatory/development strategy. Specifically, the FDA seems to have challenged the company’s choice of a single Phase 3 study using Progression Free Survival as the end point instead of Overall Survival, especially since Pfizer chose not to avail themselves of an End of Phase 2 meeting with the FDA. It doesn’t appear that Pfizer got FDA agreement through an SPA either.
The Advisory Committee will probably focus on the conduct of the study though and the role the DMC had in the decision making process other than safety. The major issue seems to be the halting of the trail with only 28% of the subjects enrolled and the predictive value of this limited number of PFS patients from a single study.
One study with limited enrollment, PFS instead of OS – I think the discussion will be short and predictable. The recommendation will be negative.
On Tuesday, April 12, 2011, the FDA Oncology Advisory Committe will hear Novartis and the FDA discuss the application for AFINITOR (everolimus) in the treatment of patients with advanced neuroendocrine tumors of GI, lung and panreatic origin. The drug is already approved for the treatment of advanced renal cell carcinoma and after the Advisory Committee meeting, I think that Novartis will have to settle for retaining that indication for the time being.
The FDA has raised questions about the value of progression free survival in predicting overall survival as it usually/always does with oncology drugs, as well as questions concerning the censoring of certain patients and whether the 2 Phase 3 trials support each other. Novartis will argue that the terms of the Special Protocol Assessment allowed for progression free survival as a valid endpoint. And, here is where they lose the argument. FDA will point out as they did at the Pre-NDA meeting that Novartis protocol amendments have made the SPA invalid. It is unlikely that the FDA will give in on the sanctity of the SPA contract. It is a contract between industry and the FDA, binding on both. In fact, the value of the SPA to the industry is the binding of the SPA. If the FDA bends on this, Novartis will win the approval and FDA will be able to say in the future that FDA can invalidate their agreements made under the SPA.
This is not the drug, nor the indication to test the contract. AFINITOR is on the market already and patients have access to it if their physicians feel it necessary for their treatment.
On Tuesday April 5, 2011 the FDA’s AntiInfective Advisory Committee will discuss Optimer Pharmaceutical’s (OPTR) drug DIFICID (fidaxomicin) for the treatment of adult Clostridium difficile. The sponsor seems to have conducted adequate studies demonstrating that the disease and the organism are both present at the start of the study and the disease and organism are not present after treatment. The FDA Briefing Document seems to pose no threat to the approval of this drug. The company has shown that the drug is both safe and effective in the indicated population. While the FDA reviewer took issue with some of the outcomes, the conclusion is identical to that of the sponsor.
There are really only 2 issues which will warrant discussion. The first is the second question posed to the Advisory Committee related to recurrence. If this question is intended to provoke a discussion on resistance, the result can only be – the bug will eventually win. Bacteria have always found a way to become resistant and they always will.
The second discussion topic might be the non-inferiority analysis. I think this will be academic, brief and in favor of the sponsor.