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Wednesday, June 7, 2017. Could AUPH phase 3 trial be terminated early because of GOOD results?

Yes. 


This is a preview for tomorrow's discussion where we will explore a number of key questions, including:

  • Why is the Phase 3 protocol almost identical to phase 2, and what does this suggest?
  • What do we learn from 2017 FDA report that describes 22 P3 trials that had different outcomes from P2?
  • The odds of for all autoimmune treatments succeeded in P3 is in fact 62%. So what is the statistical basis for the case the odds are much higher for Voclosporin?
I clearly don't have all the answers here, and will need your help so we can all improve our understanding of these issues. Doing so will allow us to improve our risk/reward assessments.

All the best,

TC 





Comments

  1. UnknownJune 7, 2017 at 4:30 AM

    It has been done before but who could stop it if the trial is double blinded. If even the management is not privy to the data how can it be done unless only the FDA is allowed to see the data. That is why I ask the merit of the blind design of the trial especially that you have only one drug and the length of the trial is over two years. Could the design have been changed after they found out the results data of P2? Unless they have multiple surprise catalysts in the next two years, I guess us longs are resigned to see the shorts manipulation in these next two years which really doesn't matter if you believe in the drug. Does anyone know how the trial could be stopped under these double blinded trials?

    ReplyDelete
    Replies
    1. Trading CyclistJune 7, 2017 at 4:41 AM

      Hey Jess, thanks for your note! All of these trials have independent, third party monitoring boards. They can stop trials for a variety of reasosn, incluring exceptionally good results or poor results that put patients at risk. I found a 2017 review of trials that were stopped, and 12% of the terminated results were the result of efficacy data (both good and bad). In the case of "good" results, the ethical I that patients in the control arm are unnecessarily being denied a treatment which has proven to be effective. More on all this shortly!

      Delete
    2. UnknownJune 7, 2017 at 4:47 AM

      Good! So it's not all blinded anyway. Ok, in this case they are the ones that can recommend to the FDA if the trial should be stopped due to great or poor results data. Thanks Blondie. Hey, if you don't like this name, say so.😉😉😉

      Delete
    3. NeilJune 7, 2017 at 5:08 AM

      I went down the early termination rabbit hole last week and what I think I learned is that DSMBs can only stop the trial for efficacy if prespecified thresholds are met. To my knowledge, no prespecified interim analyses have been planned for this trial, therefore they have no mechanism for a positive early termination. If this is not correct, please set me straight, I would love to be wrong on this!

      Delete
    4. Trading CyclistJune 7, 2017 at 5:18 AM

      Thanks Neil! From my reading last night, the DSMB does their own analyses. I'll post the source material for my claim here as soon I get a moment this morning..
      In the meantime, I promise I'm not making this up! :-)

      Delete
  2. Trading CyclistJune 7, 2017 at 5:23 AM

    Lunacy, any chance we could as you to weigh in on why we expect the probability of Voclosporin being successful in P3 is higher than the average of 62% for autoimmune treatments? I assume this is a messy story because one would have to compare the strength of prior P2 results with those for Voclosporin.

    ReplyDelete
  3. Lunacy aka John GaltJune 7, 2017 at 6:19 AM

    One good way to look at the probability of a company replicating mid-stage trial success to late stage is to take a look at P-values. Auph's 48wk data showed a P-Value of <.001, which is as good as we could've asked for. After the 24wk data, the FDA told Auph just do a single phase 3 trial with our support and easier endpoints. At the time when designing the Phase 3 neither Auph or the FDA had any idea the results were only going to get better as more time went on. Auph ended up settling on basically a repeat of Ph2b to satisfy both EU & Japan along with US with a single trial rather than going for the easier endpoints and just US approval. What that tells me is that Glickman and team are extremely confident they can produce great results again. With P-values as good as they are and almost identical endpoints, there is a very high likelihood that we will see very strong results again. On a separate note, they will have better study sites enrolled this time around and do a better job with patient selection which should help eliminate some of the issues that were seen in the low-dose arm in Ph2b.

    ReplyDelete
    Replies
    1. Trading CyclistJune 7, 2017 at 6:28 AM

      Thanks for that super quick and thoughtful response!! Now my annoying question (2). :-( First, and off the top of your head how does this compare to other Phase 2 trials that may or may not have been successful in P3? Put differently, to the best of your knowledge, are there other P2 trials that have had similar P-Values that were not successful?

      Second... (!), is it your view that, given the trial design, there would be sufficient data at 24 weeks to halt the trial (if successful) to declare victory?

      Thanks again for chiming in here!!

      TC

      Delete
    2. Lunacy aka John GaltJune 7, 2017 at 6:56 AM

      The promising Ph3 trials I've seen fail are either when the Ph2 had successful but not great P-values and then the larger Ph3 had significantly more patients enrolled. Or, Ph3 preventative vaccine trials are often very difficult to reproduce results. Or, they deviated to much in the Ph3 design from the Ph2. All of which aren't an issue here.

      I can't really speak to if/when/why/how they would stop Auph's Ph3 early due to promising results, but the issue would then be if the data available was sufficient enough for EU & Japanese approval as well. They wouldn't want to jeopardize that.

      Delete
    3. Trading CyclistJune 7, 2017 at 7:09 AM

      Thanks Lunacy! Here's the link to the recent FDA study on 22 p3 trials that didn't replicate the P2 results:

      https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UCM535780.pdf

      I have only skimmed this, so am unable to say anything insightful about it... (!).

      Cheers,

      TC

      Delete
  4. Lunacy aka John GaltJune 7, 2017 at 12:45 PM

    Making headlines again...

    https://lupusnewstoday.com/2017/06/07/lupus-nephritis-investigational-therapy-voclosporin-benefits-demonstrated-by-clinical-trial-aurinia-says/

    ReplyDelete
    Replies
    1. Trading CyclistJune 7, 2017 at 1:50 PM

      All good. This stock will most certainly require a lot of patience!

      Delete
  5. Trading CyclistJune 7, 2017 at 2:30 PM

    Fyi only, our site is now getting about 1,000 hits per day (950 or so).

    ReplyDelete
    Replies
    1. Trading CyclistJune 7, 2017 at 6:46 PM

      943 for the day. About the same as yesterday. I think this traffic is probably every bit as LieHub...but without all their bullshit.

      Delete
  6. vidpok45June 7, 2017 at 5:34 PM

    Just wondering if anyone has any thoughts on tomorrow's testimony by Comey as regards its effect on the market in general and our stock in particular. If the testimony is as damaging as I suspect it may be, I think we will see the markets use this as an excuse for a significant decline. Having said that, I think the effect on our sp will be negligible or slightly positive as AUPH has plenty of COH and doesn't currently have a product whose earnings will be affected by a downturn in the economy. The markets have been looking for an excuse for a major correction for a long time. Comey's testimony may be the impetus for that selloff if it looks like an impeachment may be forthcoming imo.

    ReplyDelete
    Replies
    1. Trading CyclistJune 7, 2017 at 6:44 PM

      If the old adage that markets don't like uncertainty is true, we may well be in for a ride. That said, not of the drama of Trump's first term has had any impact . So my bet is there's no response from Wall street, generally, and nothing to derail AUPH specifically. But we shall see!

      Delete

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