This is my first post here. Couple of observations. Wait for the subgroup analysis, these results do not make sense and partly its because the sites were dispersed over US and EU and they included NYHA Class two patients who rarely go to the hospital as they are less sick. Mydicar has a different mode of action for AV fistula maturation which is a huge unmet need. As per last CC they were planning phase two trials this year for this indication. Those trials are not very expensive and if memory serves right should not take more than three months.
Thank you, that is helpful. I have also read your previous posts and its rare to find someone knowledgeable and articulate.
" I expect they have already dug deeply into sub-groups in search of something positive to put into their press release."
In the post disaster conf. call the CEO stated they had not done so and would do it as soon as possible. So in your estimation if we don't hear anything about it in the next two weeks there is likely nothing positive there? They did state they would publish the full results and present them at a conference.
I am hopeful something might come of the subgroup analysis. I think there are three potential factors affecting the delta between the placebo and the sick patients. Firstly including the NYHA Class Two patients makes no sense, they do not require hospitalization ! Adding them decreases the magnitude of the percent difference between the two groups(assuming they are equally distributed in both groups). Secondly there is a lot of variability in health care between here and Europe. A Class three hospitalized in the US is likely to be managed at home in Europe where Primary Care Physicians shoulder a lot of this kind of care unlike the US.
Thirdly the role of antibodies to Mydicar adds more variability.
I am hoping they might be able to identify a small group say Class IV patients in the US who were antibody negative and showed a strong statistical difference. This might be the basis for their next clinical trial and the FDA might allow them to sell the drug for this particular indication in this group as these patients really have no alternatives except LVAD or transplant.
The good thing is only Class three and four NYHA patients. We will know the answer by the end of the first phase in 2016 Dec.
I agree with you, "Big Pharma" is out and onto the next minnow.
" hope she is wrong when she says no-subgroup review had been done; because I wonder why on God's earth would you call a news conference about a global result only, when sharply differing sub-group responses may washing each other out and thus giving you an uninteresting global statistic? If her statement is true, then I suppose no one in her company has had Statistics 101."
I think by law they are allowed to hold onto material information only for 48 hours before they have to disclose them to the public. The longer they hold onto the information, the more risk they run of someone in the know acting on it and compounding the problem with a SEC investigation on top of a dismal result.
They have a phase two on AV fistula maturation which is a huge unmet need in dialysis. Uses different therapeutic action from Mydicar. As per the CEO they plan a phase two trial on it this year. Should not take much cash and not more than three months.
The problem partly I think is that they are still blinded; this is standard protocol in case they need to do something else. The FDA is very strict about this. Once they get the data the questions go back to the committee guiding the study and they run the statistics and get back to them.
You are welcome! I am cautiously optimistic about the subgroup analysis for stage four NYHA category. Examine the data from Cupid 2 at 3 yrs (survival).
Placebo- 13 deaths out of 14-93%
The high dose was the one for this trial and if my recollection is right the one patient who died in the high dose was the one with antibodies so mydicar would not be effective.
IMO they would not permit that. That's statistics101.
I think a big part of the problem is including class Two patients; in the original protocol they had included only class Three and Four NYHA. I am not sure what made them include Class Two. I suspect there were not enough subjects in Class Three and Four as there is intense competition for those patients with multiple LVAD trails goings on in the US and Europe.. They have not released the patient details but I bet the majority of them are Class Two, which would explain the small non significant therapeutic benefit.Unless there is a strong subset therapeutic effect for Class Three and Four this trial is doomed.
Could you give me the source for the information you quoted about 16% Class Two patients in the Cupid2b trial. I would also like to understand the basis for your assertion that the dose is not effective in Class Four but effective in Class Three. Thanks.
I believe there was an article by a Mr.Zheng on the seeking alpha site (part which requires a subscription) about abnormal signals from trial analysis. I am not privy to the article but from the title seems to suggest a favorable outcome to possible subgroup analysis IMO.
Since you have not replied to me but have been posting on this message board I assume you have no answers. I think you got the effectiveness in Class three and not four from the last study in which all patients in the high dose were Class three. I still am not sure where you got the 16% Class Two in Cupid 2b from.
I did some more digging and in response to your allegation, stratification in this present Cupid2b trial was by country and walking distance of at least 150 meters. Only patients in Class two can walk that long so I assume they stratified Class two separately and lumped Class Three and Four together.
You are right about it not being naked shorting and most of the majority institutional investors selling out causing the drop. I also think Big Pharma is holding as is pavisa ( and me) till the details are out. By the end of next month we all will know whether the trail failed magically because a drug that improved survival by 90% compared to placebo stopped working or because the trial was poorly designed and failed but the drug still works for a section of the population. To each his own. Good Luck!
I have been reading some of your posts here and on seeking alpha. You are in the biotech industry and I accept your description of patient demographics and I will not ask you to reveal your source. I am trying to model their results and perform some analytics on the 2b trial results. The only info on the net about this trial ( that I could find ) is "Randomization and Blinding
Subjects will be assigned in a 1:1 ratio to MYDICAR® or placebo. Randomization will be stratified by country and the ability to walk between 150 to 425 meters in the 6MWT." In my model if I stratify Class Two as 20% and Three and Four as $40% each and assuming no effect on stage two and four patients and a 50% reduction in hospitalization in 2/3 of the Class Three patients; I get a figure similar to the hazard ratio they got. This is obviously a very simple model and has to be wrong as the information is incomplete. This shows a trend for Class Three but is not statistically significant. Obviously if there is no stratification this model does not apply. Can you give me your thoughts? Thanks.
Thanks again. The only stratification I can find in Cupid 2b is by country and a modified 6 minute walk test where the subject has to walk 150-450 meters. I have been looking at the walk test and its not very sensitive in the short term and does a poor job of stratifying NYHA Class. In the figures you have given above both for Cupid 2 a av. distance was 345 meters and in 2b 326 meters implying that all CHF patients except the very severe Stage four who are dyspnoeic at rest would be able to walk 150 meters. This means stratification was by country and in terms of CHF there were two groups severe stage four and the other group was stage two, three and milder stage four patients. This would definitely lead to uneven distribution of stage two, three and four patients in the two arms. Would you agree with this?
I hope sooner! Its only 250 patients. Its really hard to explain that a 88% risk reduction at one year with a p value of 0.003 would be reduced to a 8% improvement with a p value of 0.8 unless there are serious issues with the trial.
The factors you site were really peripheral to my decision to invest.
I made my decision on two facts which stood out to me. First the One Year Relative Risk reduction for the highest dose which was employed in the 2b tail was 88% at a p value of 0.003 and at three years there was a 90% reduction in mortality at 3 years compared to placebo. These are incontrovertible findings and the fact that on average the mortality and morbidity rate in placebo follows general accepted cardiovascular trial morbidity and mortality curves proved to me the noise about placebo patient patients being less sick was just that noise. I also realized since Mydicar was not improving Ejection fraction it was merely stabilizing the heart but as long as it was reducing hospitalization and mortality it did not really matter to me.
Where I erred was in not realizing the impact that adding two previously untested groups ( Class two and Class Four) and lack of proper stratification would play havoc. This is the opposite of what ACAD did. They had a failed phase two but certain subgroups showed clinical significance and they concentrated their phase three trial on those subgroups and worked hard to reduce the subjectivity by rigorously training the observers and succeeded in their phase three. CLDN in contrast had one
dose work in one group of patients and they messed it up by including other groups of patients and not stratifying properly. Corporate Greed at its finest!
Management is inexperienced and panicked and anounced the topline results which include three groups of which only one group was evaluated in the previous 2a trial. That group showed a 90% efficacy witha p value of 0.003. It is very possible that particular subgroup would show efficacy or a favorable trend on further analysis.
Its not him; the shorts are taking position. Look at the volume.