I responded to AFs Jan 31st blog where he dissed apaziquone. He’s not going to respond since he didn’t respond to anyone else but it felt good and made the case for provisional approval. Here’s what I posted.
Adam, you are correct in that if you only submit one study (or combining the 2 studies) to the FDA you need a p value of 0.01 and if we left it there you’d be right. But we also know that the FDA, in looking at the data, is willing to have an Advisory Committee meeting to review a potential NDA for apaziquone. And we know that SPPI has agreed to another P3 study for single instillation. And with almost absolute certainty, the 3rd study will have a p value of less than .05 since SPPI clinicians and statisticians know that 800 patients won’t cut it and 1600 patients will do the trick in order to get the appropriate p value of under .05. Will it be 1100 patients? 1200? 1300? They surely know the answer to this. Or if they don’t, just run a 1600 patient study to get a p value of ~.0178 which is way better than .05. That’s why I believe the FDA will give provisional approval since the 3rd P3 study will come in with a p value of under .05 and Eoquin meets the criteria of having 2 studies with a p value of under .05 ( i.e. .0178 and .05). Why else run this study without getting conditional approval if in all likelihood the 2 P3 multiple instillation studies SPPI is running will be finished and submitted to the FDA before the single instillation P3?
The provisional / conditional / accelerated (all indicating the same thing) approval is not a stretch. A conditional approval model already exists, in the FDA’s accelerated approval process for serious, life-threatening diseases. Some examples include Genentech’s Avastin which was conditionally approved for breast cancer but did not show a benefit in the newer trials so the F.D.A. removed the approval for breast cancer and AstraZeneca’s Iressa that also had been given accelerated approval based on its ability to shrink tumors but the FDA curtailed its use when trials showed it did not prolong survival.
You state (and let’s ignore the bad sentence structure) “Bad news, except in the alternative reality where Spectrum and its diehard supporters reside”. It seems to me that with regards on how apaziquone fate will turn out its more apt to say “GOOD news, except in the alternative reality where SHORTS reside”. But you are absolutely correct in your statement “For everyone else not wearing clown hats, let's do some truth telling about apaziquone”. Adam, it’s not too late to do so!
just wondering.............based on data from multiple instillation tria on apaziquone by sppi....... i take note that the trial population is not sizable. wonderring , in light of the previous 2 apaziquone trials that did not meeet primary endpoints. was"nt the reason for the fail said to be because each trial of 800 patints each was too small to generate significant p -value ? it was poste that the fail was due to poor trial design/cost savings to sppi............QUESTION,, will this same probleem arise with the new multiple instillation trial ? again look at qty of patients being used for such trial. is trial design ok ?? just wondering how more knowledgeable folks feel on this issue.
Thanks all for the good discussion. Just to clarify, the reason I don’t see final approval is based on combining the 2 existing studies with a p value of .0178 (better than .05) is as per Sharon’s comment that the Credit Suisse report (available on Etrade) mentioned that if you only submit one study you need a p value of .01. I wouldn’t take Adam's word but CS is saying it also. My reasons for provisional approval are discussed in my original message and I still believe in that. We’ll see. I will also look at some of the links/comments you provided when I have some time.Thx.
"Adam, you are correct in that if you only submit one study (or combining the 2 studies) to the FDA you need a p value of 0.01 and if we left it there you’d be right." Are you sure that you need p value less than 0.01? AF could not provide any reference for that. He made a mistake.
Dear Antihama, I think I had made a strong case for FDA approval. It would be terrific not only for Spectrum, but all those who have waited for nearly a quarter of a century for something better than repeat surgeries and damage to other organs. If there are questions why this drug should not be approved, why not send a questionnaire to those with bladder or surviving family members.
Do not forget Apaziquone has no competition. Also, one instillation of a radioactive drug beats 10. Did you read my 10 year plan? This is a huge improvement. Even Apaziquone can not cure a new cancer, but what if a "booster" instillation every year is given? That could prevent new cancers and because there is so much less radiation used , there may not be new cancers.
Bladder cancer is more frequent in men and large amounts of radiation could increase risk for prostate cancer or any cancer since radiation causes cancer. Maybe it's just me, but I cannot find a compelling reason for the FDA not to approve it simply because it is safer. Recently, the FDA changed Vicodin 750 with750 mg. of Tylenol to 3.50 mg. of Tylenol. Why? It is safer since high amounts over time is toxic to the liver.
Could be wrong, but isn't radiation not good for you? Of the two, I think I'd take my chances with Tylenol. . So, the FDA has approved three drugs on pooled data and they have cut the amount of Tylenol 50% with Vicodin. How could they not approve it ?
I see a lot of people getting too excited about apaziquone's future, but in my humble opinion, everybody should keep their expectations low... There is no doubt that apaziquone works, and that it is safe. But if efficacy was good enough, the trials would have shown a p-value statistically significant.
What I read in the Apaziquone PR is that the quality of the trials is enough to sustain a New Drug Application, not that the FDA is willing to accept one. There is clearly no anticipation of any outcome, in fact, the need of an advisory committee means that the approval is far from being an slam dunk. A third phase III trial is required, whose design will be established by(or at least agreed with) the FDA. This fact might limit its chances of success(a similar trial to the two already conducted would likely fail again).
Apaziquone is not the treatment for bladder cancer, transurethral resection is. So, the way I see it, there is not such thing as an "unmet medical need" in this case. Apaziquone aims to reduce recurrence rate and extend the time to recurrence, sort of the same thing that zevalin does in the consolidation setting for follicular lymphoma, but not so well as zevalin does.
Apaziquone right now is a lottery ticket, and it is more likely than not that we don't win, but with the recently readquired rights, the potential price is bigger.
I'm with you on Eoquin. For those who think its an "unmet medical need", please do further research. TURB is the standard of care.
As to safety, not sure how much safer it is than standard treatment after TURB; ie. mitomycin. no detail data reported by SPPI.
What if Eoquin did n't have the opportunity to be efficacious enough merely due to "math"? Population was too small for both trials. TURB was just more effective now with new technology/technique than in the 1990's and as such failure rate was too low? We had this discussion almost a year ago.
"But if efficacy was good enough, the trials would have shown a p-value statistically significant. "
With new trial, it better not be the same trial end point of 2 yrs. we can't be waiting 5 yrs from now for results. that is ridiculous don't you think? Its merely doing a large study with intent to enroll 1,600 patients. But 5 yrs for results? And FDA better NOT request a head to head against mitomycin or current approved drugs; else eoquin will fail immediately!
Sentiment: Strong Buy
If you put in: Tafamidis Meglumine NDA 202737, You will find this is a FDA publication on an evaluation of a NDA. On page 4 it states: "study positive only if P-value for both
Sentiment: Strong Buy