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Amicus Therapeutics, Inc. (FOLD) Message Board

  • A Yahoo! User Dec 24, 2012 5:32 PM Flag

    Trial Composition

    I looked up the previous phase 3 trails for the IV Enzyme Replacement phase 3 studies and both the studies used all males in the treatment and placebo group. None of the placebo patients showed any improvement in those trials.
    Does anyone know why FOLD decided to have twice as many women as men in their trials. It seems clear this is what is responsible for the improvement in placebo patients as women are heterozygous and so have more variability for this X linked chromsomal defect.

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    • I have to think that they did know how the trials would be. First placebo, and then advanced to acquire comparisons in last 6 mo data. I do not have a background in science but common sense
      tells me that the horse goes before the cart. I am holding tight and hoping for a smoother ride. I didn't like how this traded the last two days before they released the data. They either had a badly
      designed trial or it was purposely designed to be questionable. The lack of clairity from management also has me confused. A statement as to why, would not comprimise their presentation in Feb., or their results. I do believe we will prevail, and this will turn out well, but there are going to be issues along the way, as we have encountered.

      Sentiment: Hold

      • 1 Reply to paveneerlogs
      • I agree with you; I did not like the way the stock traded the two days before release of data; they can hold onto the data for 48 hours before releasing it as per Sec rules and I am sure insiders were selling. I thought of selling too but ACAD traded similarly and did well (I was in it ) so I held on. In hindsight it was a mistake.

        Regarding trial design; this is identical to what was used before for the ERT trials and was approved by the FDA so there did not seem to be a reason to deviate from the pattern. As they say hindsight is everything.

        I agree with your asessment; we will prevail ( at least in some fashion ) and sooner than most people expect but it will be a bumpy ride.

    • I appreciate your position and agree with all that you say, but it brings me back to your first post as to why they would include twice as many women, as they knew it could be a game changer. I am confused as to their intention. The 6 mo data should have been analyized and released at the end of the 6 month trial, not nearly 6 months later. I see this as a bad decision made by some very smart people, unless they had some unforseen reason. I'm sure you have thought about it also. It would be hard to consider that the trial was set up in this manner, knowing they could devistate the
      pps as it has.

      Sentiment: Hold

      • 2 Replies to paveneerlogs
      • They did not have any control on when they could look at the data; I believe it was dictated andagreed to with the FDAas part of the design protocol. Most studies like this are set up similarly. Dont forget the placebo group is not only being compared to the treatment group in the first six months but also to itself in the last sixmonths. Its important for them not to know theyare in the placebo group so as not to influence results.

        As to why they used women and in fact hada 2:1 bias for them; I dont know; their other trial comparing migalstat to ERT also has women in it. Interestingly enough it does not evn bother to estimateGL3. Primary endpoint is GFR and whole host of secondary endpoints looking at function in diferent organs and QOL issues. My best guess is that they think migalastat will be more effective in women. For migalstat to function there has to some amount of enzyme being produced. women being heterozygote have more chancesof having some enzyme. This is purely a guess. I think one thing the management can be faulted for is not thinking of the variabilty this would introduce in the placebo and control group particularly in regards to GL3.

      • This is why I think something's cooking!!!

        Sentiment: Strong Buy

    • Thank You for your reply. My question then to you, Do you believe as I do, that the results for the 6mo trial, had been Presumed by management to be what it is, and that the data would be, {could be} negative? I am leaning toward 12mo positive, and almost confident that if Pompe trial is positive, then 12mo will be also.

      Sentiment: Hold

      • 2 Replies to paveneerlogs
      • I think Management and GSK both got blindsided. At the end of six months they looked at the blinded data and saw 22 (13 plus 9 ) patients responding. They assumed most were from the treatment group as there is no reason to expect a significant no. of placebo patients with a disease like Fabrys to respond. The trial was set up that a difference of 9 additional resonders in the treatment group would make it statistically significant. This is why they were able to bargain with GSK and get US rights as both FOLD and GSK thought they were on a homerun. Hence the heavy insider buying.

        The thing to remember is the drug works! Fabrys patients if they are not on ERT get lot of pain in their hands and feet apart from other complications. The fact that you have several of these patients staying on migalastat for years now means it is working. My best guess is that the six month data will show a trend towards improvement in all parameters; if we are lucky it will be statistically significant. I am almost certain that the twelve month data will show a clear clinically meaningful and statistically significant improvement.

        With Pompes its a different situation, they are giving the drug with ERT ; similar to the Fabre Trial with ERT. All data has been positive so far (for both) and I am fairly confident it will be positive. The issue is that it has to be clinically meaningful i.e. you get much better clinical response in some fashion or you can decrease the no. of infusions these patients have to get. The jury is still out on that one. If they proceed to stage 3 that means there is some clinical benefit as they will not take a risk; particularly now.

        These are my guesses FWIW. Good Luck!

    • I have questioned in my mind, why did they wait to release the data for 6 mo. trial. I never implied that management was stupid. But now that I am thinking about these trials, I believe that they knew all along what outcome to expect. BIG P is here to make money. The trial design was this way for a reason. The presentation of failure was delivered without an explaination. A short, " this is why," would not have comprimised their future presentation in Feb. on results at 6mo. or 12mo.

      Sentiment: Hold

      • 1 Reply to paveneerlogs
      • I did not mean to imply that you thought management was stupid; it is that we question management when they are doing exactly what they said they would do. If you look at their previous presentations they said they would remain blinded to the six month results till the trial was complete. The trial completed in December and that is when they unblinded the results.
        I might be wrong but someone on the board suggested that they did not want GL3 as the primary endpoint but rather kidney function but the FDA insisted on GL3. Their head to head comparison trial with ERT has only Kidney function as the primary endpoint. I think they did not say anything because they do not want to offend the FDA by saying GL3 is not as relevant as kidney function

    • kartallaryuksektenucar kartallaryuksektenucar Dec 26, 2012 12:26 PM Flag

      I still think the drug works. It is the trial design that made the results look bad. There is of course the possibility that the 12 month data achieve statistical significance but don't be surprised if they require to do another PIII this time by men only. The stock will be trading (down-to-flat) purely based on technicals until further clarification is released.

    • whats your take on a release of pompe study results as far as when and what?

      • 1 Reply to makemy2005
      • As to the release I do not think they will do it before people at wall street return to work; earliest in my opinion is the 3rd of january. As for the results for Pompe they are releasing results of two separate studies as I understand it. One is the Phase Two Study and another a study on immunogenecity. If in the phase two they can show an increase in enzyme activity in the muscle biopsy on both day two and seven and on the second study if they can show a decrease in immumnogenecity with Co administration; we are on a homerun. The phase two study has just shown a trend in increased enzyme activity but far from conclusive.

        Thse are only my opinions FWIW.

    • I agree, but I am also wondering if there could be a problem with the data, not the trial. Management is not forthcoming with enough info. Longs have every right to question their integrity. Why haven't they given an explanation? Is this another way to get us to sell our shares for big P, before final data released.

      Sentiment: Hold

      • 1 Reply to paveneerlogs
      • You can call the management whatever you want but they are not stupid. They had said they would only release the topline data and save the rest for release at the conference in Feb and this is what they have done.
        Fabrys treatment is not given to females usually as they are heterozygotes unless it can be proven they have a significant enzyme deficiency insurances will not pay for treatment. To do a trial with prepondernec of women in this case would be to expand the label but these kind of trials are usually done after the FDAapproves the primary label. There were around ten males in each (controland placebo group). I am no statistician but if the variablity was confined to the females and males could be statistically calculated as a subgroup and all subjects showed improvements at twelve months they might be able to get away with it. Maybe they already hava an agreement with theFDA to do something like this. Dont forget they also have a another trial with head to head comparison with IV enzyme replaecement reporting in 2014.

        As you said something here is not allright and I plan to hold on to my shares. It might be dead money for a while but I think in the end we might do OK

    • This was a monumental error, and there should be separate class action suits, one from the Fabry sufferers who will never have access to the drug, the other from investors who lost money in the stock. They should never have allowed even one woman into the trial. Everyone suffers from that one idiotic mistake.

      The other mistake (using random unreliable biopsies rather than urine tests) is owned by the FDA, I believe.

 
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