Well, the company has pooled the data from the trials and somehow managed to eek out some level of statistical significance, and demonstrated a 7% reduction in recurrence. It’s this 7% that Spectrum Pharmaceuticals, Inc. (NASDAQ:SPPI) is basing its application on. There’s an additional kicker, but it’s a long shot: the company has stated that the drug can be used in patients that have a perforation in the bladder – something that the current off label drugs aren’t suitable for. It suggests in the application that a large number of physicians don’t administer the current off label chemo agents because of this perforation related potential setback, and that an approval for apaziquone would offer a solution for these patients and – in turn – increase intravesical chemotherapy usage. However, in a single, third party, study that recorded the reason immediate intravesical chemotherapy was not given, a deep resection (and therefore possible perforation) was reported in just 9% of patients. That Spectrum is using this 9% as a potential reason for approval is a real straw clutch in our opinion.
These numbers aside, there’s an even more important (and damning) point.
The vast majority of physicians don’t use this sort of treatment (by way of the above discussed off label drugs) because they don’t deem 12% to be a worthy clinical benefit. That’s a 12% reduction potential. Even in the pooled analysis, tacked together by way of an ad hoc, post analysis hypothesis, Spectrum has only managed to demonstrate a 7% reduction. As such, even if the FDA were to approve the drug in this indication, there’s a very low chance of physicians actually using it. To put this another way, if they don’t use a drug that creates a 12% reduction benefit, what would make them use a drug that creates a 7% reduction benefit?
So this brings us to the advisory panel review. As mentioned, the panel voted against approval, on the back of the above mentioned points. Here’s what the agency said to the panel heading in to review day:
The Agency’s primary concern is whether the Applicant has demonstrated substantial evidence of efficacy. Substantial evidence ensures, through well controlled and well-conducted clinical trial(s), that a treatment effect has been identified and is not due to variability in the underlying disease, bias, or chance alone.
- VOTE: Has substantial evidence of a treatment effect for apaziquone over placebo been
demonstrated?
- DISCUSSION: For those who voted “yes” to question 1 that an effect has been demonstrated, please discuss the clinical meaning of the results of studies 611 and 612 (these are the numbers used to reference the trials we’ve already looked at.
All 14 members of the panel voted against the approval of the drug, which renders the second element of the FDA’s questionnaire, the DISCUSSION element, moot. Essentially, the panel said that there was no evidence that underpins an efficacy hypothesis, and that to replace the current off label treatments with a drug that is – at best – two thirds as effective, doesn’t make any sense.
Spectrum Pharmaceuticals, Inc. (NASDAQ:SPPI) is conducting a Special Protocol Assessment right now, aiming to demonstrate the impact of two doses, but the chances of this affecting the outcome are very slim, if not nonexistent.
We probably don’t need to stress our opinion on this one, but for the sake of drawing a conclusion, here’s our take:
Apaziquone is not going to get approved. It’s ineffective and unnecessary, and the kicker of perforation related usage (which wasn’t even brought up as part of the panel questions) is nowhere near a strong enough point to influence the FDA’s decision.
Readers can check out the documentation at the following links:
