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  • Genervon ALS drug shows encouraging results [View news story]
    I am not adverse to using historical control, but there are uncertainties. The statistical significance suggested in this case is based on the difference in the downward slope of the ALSFRS-r lines for the drug group and the historical control group. There is great subjectivity involved in coming up with the slope of historical controls; this can be highly variable depending on the patient characteristics of drug group versus historical control and the time interval over which the slope is determined. Also, in the BENEFIT-ALS trial there is strong evidence of a placebo effect. I know that some KOLs are saying that the time frame for judging the true slope of the ALSFRS-r data should be done over a one half year to one year time frame. If this is true, the drug group in this trial which was followed for three months could gave benefited from a placebo effect. I readily admit that this is all conjecture on my part. However, in a clinical trial that is randomized, the company should first report results for the drug versus control and then if they want to show the results versus historical controls fine. Based on the data they have presented I think that we can only say at this point the drug was safe in this trial. I am curious to see all of the results and I am particularly interested to see if there is stability or improvement in the control group which would signal that there is a placebo effect. My guess is that there is.
    Oct 23, 2014. 05:24 PM | 1 Like Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    I suggest that you read my report that goes into issues for the possible phase 3 trial.

    http://bit.ly/1yplkPq
    Oct 23, 2014. 09:20 AM | Likes Like |Link to Comment
  • Genervon ALS drug shows encouraging results [View news story]
    I see that this is the first time that you have ever made a comment on Seeking Alpha. I suggest that you go back and look at my prior comments on CUR to to understand the research that I have done. See this link http://bit.ly/1yp6mJb
    I readily admit that I make lots of mistakes. That is inevitable when researching pardigm changing technologies. However, I don't think that you can accuse me of "making statements off the handle without doing your own research."

    Oct 23, 2014. 08:01 AM | 2 Likes Like |Link to Comment
  • Genervon ALS drug shows encouraging results [View news story]
    I have no intelligent reply at this point.
    Oct 22, 2014. 07:22 PM | 1 Like Like |Link to Comment
  • Genervon ALS drug shows encouraging results [View news story]
    I spoke with them in detail about their technology. In the conversation we had, they explained it as a master regulator of transcription factors that control gene expression throughout this central nervous system, According to the Company. this master regulator peptide can correct malfunctioning of genes in the CNS and therefore have a direct effect on any disease that occurs in the CNS, not just ALS. This is the first time that I have heard of this biology and the attempt to harness it. In doing further research based on this conversation, I have found some academics who are working in the area and hope to have a conversation with them. As you may know, I have a keen interest in ALS through extensive work I have done on Neuralstem and Cytokinetics and I am fascinated by new ideas. At this point, I have no opinion on whether this has the potential to be developed into a commercial product.

    In addition, I was curious about the decision of the company to compare the results of 8 ALS patients treated with their drug to an historical control rather than the four patients who were randomized in the trial. To say the least, I found this strange. They gave me no information on these four patients other to say that there was no statistically significant difference on the ALSFRS-r scale between drug and control. They would not confirm whether results were the same, slightly better or slightly worse for the drug,just that there was no statistical significance. This was a small part of the conversation although important. Everything else in my website article is based on the press release. The link to my article is http://bit.ly/1tclESj
    I am not adverse to using historical controls as they can be important. However, it is difficult to find data that might suggest how placebo patients in other ALS trials might perform over a three week period on the ALSFRS-r scale. The ALSFRS-r scale is highly subjective and subject to placebo effect in the short term. Some key opinion leaders have suggested that the ALSFRS-r scale might be best used to measure therapeutic effect at one year or greater intervals because of this. I have suspected that this might have played a role in the failure of the Cytokinetics" BENEFIT-ALS trial.
    The Company has also pointed to results in some biomarkers that were tracked in the trial and which the Company pointed to in their press release as being predictors of outcomes in ALS. There are no validated markers for ALS that I am aware of. Given this and my lack of understanding of the biomarkers they were using, I spent no time on biomarkers. However, the FDA is extremely keen in finding markers for ALS and if this company has done so, it would be important. Also the principal investigator in this trial, the distinguished Merit Cudkowitz of Mass General, is very keen on coming up with biomarkersfor research. Again, this is something that I am interested in looking into.
    Oct 22, 2014. 02:15 PM | 3 Likes Like |Link to Comment
  • Genervon ALS drug shows encouraging results [View news story]
    Doug. In this trial the four placebo patients did as well or better on the ALSFRS-r scale than those on the drug. The company faced with this disappointing result that showed GM640 was no better than placebo searched the literature and compared the drug results in these 8 drug treated patients to an undisclosed group of historical controls. This must be viwed with great caution. Also, the numerical improvement in FVC was not statistically significant and could well have occurred by chance. In your bullet points, you suggest that this drug produced statistically significant improvements in ALSFRS-r and is disease modifying. The correct interpretation is that there is no difference between GM640 and placebo on the ALSFRS-r scale, there is no evidence of a clinical benefit and there is certainly no evidence of a disease modifying effect. The only thing that can be clearly stated about the trial is that in this small 12 patient trial there were no safety concerns and no clear clinical evidence of a therapeutic effect.
    Your article seems to have been the cause of a decrease in the price of Neuralstem from $3.05 on the close on October 17th to and intraday low of $2.12 on the next trading day October 20th and the stock is now trading at $2.69. Would you consider issuing a retraction or clarification of your article in line with the analysis I have made.
    Oct 22, 2014. 10:20 AM | 2 Likes Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    Valid point.
    Oct 21, 2014. 08:21 PM | Likes Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    Absolutely correct.
    Oct 21, 2014. 02:43 PM | Likes Like |Link to Comment
  • Genervon ALS drug shows encouraging results [View news story]
    In the press release, it said that in the ALS trial that there were 8 patients randomized to drug and 4 to placebo. However, the press release stated that the drug treated patients were compared to historical controls rather than the four placebo patients randomized to the trial. This is very strange. Also, we have only aggregate data on the 8 patients and no baseline or endpoint data on the 8 patients in regard to ALSFRS-r or SVC. This makes it very difficult to interpret the data.
    Oct 21, 2014. 10:15 AM | 3 Likes Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    Obviously, tirasemtiv will not cure ALS which is a syndome, not a distinct disease, that may have hundreds of different causes. However, I think that a very significant percentage of drugs treat symptoms of disease. I would offer blood pressure lowering drugs, cholesterol lowering drugs and protein pump inhibitors for ulcers and GERD as interesting examples. The last I checked, these products seem to enjoy widespread usage.
    Oct 21, 2014. 10:06 AM | 1 Like Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    I understand your cynicism. However, it is not a universal rule that once a drug has failed a phase 2 or 3 trial that that there is no hope. Consider Acadia's pimavanserin and Puma's neratinib.
    Oct 21, 2014. 07:02 AM | 2 Likes Like |Link to Comment
  • Cytokinetics Is Planning New Phase 3 Trial For Tirasemtiv In ALS Using New Endpoint [View article]
    The mode of action of tirasmetiv is to increase muscle contracility. Its function in maintaining or improving respirations is to increase contractive force of muscles involved in respiration. It does not affect the steady deterioration of the motor neurons that are dying and that result in the decrease in muscle contractility. Given the same amount of neuronal stimulation, there is increased contractility. It is treating symptoms and not the cause of the disease.
    Oct 20, 2014. 01:33 PM | 1 Like Like |Link to Comment
  • Discovery Laboratories: Collaboration With Battelle Is Validation Of Aerosurf's Potential By A Sophisticated Third Party [View article]
    You are correct that many phase 3 trials fail after apparently successful phase 2. However, in the case of Aerosurf we know that lucinactant is safe and effective because it is the active pharmaceutical in Surfaxin. The issue is whether the device can deliver sufficient amounts of lucinactant throughout the lung, As I mentioned earlier, this is more of an engineering than a drug development issue. Also, we know that the capillary aerosol generator drug device combination has been successful in lamb and pig models. All of this suggests to me that if it is established in phase 2b that adequate amounts of drug are delivered that the chances for a successful phase 3 following a successful phase 2b are much, much higher than for a new therapeutic entity. Obviously, nothing is for sure in biology.
    Oct 18, 2014. 06:23 PM | 4 Likes Like |Link to Comment
  • Discovery Laboratories: Collaboration With Battelle Is Validation Of Aerosurf's Potential By A Sophisticated Third Party [View article]
    Phase 2b will show proof of concept and, if successful, believe me that will move the stock. Why do you believe otherwise?
    Oct 17, 2014. 10:05 PM | 3 Likes Like |Link to Comment
  • Discovery Laboratories: Collaboration With Battelle Is Validation Of Aerosurf's Potential By A Sophisticated Third Party [View article]
    I can think of no greater insult than being likened to AF.
    Oct 17, 2014. 04:58 PM | 3 Likes Like |Link to Comment
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