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Lions Gate Entertainment Corp. Message Board

bigsmartsta 601 posts  |  Last Activity: 5 hours ago Member since: Apr 21, 2005
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  • 1- Since 7-months remain in the clinical trial and near 25-months have been completed, the trial span is 32-months.

    2- Therefore data is known for 25 divided by 32 of the patients or 78% of the patients.

    3- With data known for 78% of the patients and the FDA BREAKTHROUGH THERAPY designation is still with us, I see this as GREAT NEWS.

    4- Each month going forward, the known data for more patients will exist, and I find this really great if the BREAKTHROUGH THERAPY is maintained. This would send a clear message of a very successful trial.

  • bigsmartsta bigsmartsta 6 hours ago Flag

    The Time window for the secondary outcome is 52-weeks (ONE YEAR) and that is the largest number a patient can receive for the secondary calculations.

  • bigsmartsta bigsmartsta 6 hours ago Flag

    3- Secondary Outcome Measures: •Time-to-terminal event (all-cause death, heart transplant, LVAD implantation) in the presence of recurrent events. [ Time Frame: From administration up to 12 months ] [ Designated as safety issue: No ]

    4- The way I read the above is:

    Assume that 14-weeks after enrollment, the patient :
    a- Is Dead
    b- Has a Heart Transplant
    c- Has an LVAD implant

    Then that patient is assigned the number '14'. That number is assigned to either the CONTROL arm or the MYDICAR arm, depending on which arm the patient is enrolled in. All the patients' numbers in each arm are added. The Arm with the HIGHEST number is deemed the BEST TREATMENT

  • 1- Primary Event as defined in clinicaltrials gov: "Time to recurrent events (HF-related hospitalizations, ambulatory worsening HF) in the presence of terminal events (all-cause death, heart transplant, LVAD implantation) "

    2- The way I read the above is:

    Assume a patient is admitted to the hospital 12-weeks after enrollment that eventually leads to:
    a- All cause death.
    b- Heart Transplant
    c- LVAD implant.

    Then that patient is assigned the number '12'. That number is assigned to either the CONTROL arm or the MYDICAR arm, depending on which arm the patient is enrolled in. All the patients' numbers in each arm are added. The Arm with the HIGHEST number is deemed the BEST TREATMENT.

  • bigsmartsta bigsmartsta 12 hours ago Flag

    The reason is simple:

    1- No news indicates the BREAKTHROUGH THERAPY designation is still in force.
    2- The hospitalization number has not been reached by May 2015.
    3- Therefore, from 1) and 2) it must be assumed that the hospitalization number for CUPID has not been reached because the efficacy of MYDICAR is truly outstanding without peer. A truly HUMONGOUS positive.

  • If there is no news for CUPID and May 2014 or beyond is reached, CLDN is an enormous BUY.

  • Reply to

    Looking at Cupid 2 trial design

    by cash2go Jul 28, 2014 2:25 AM
    bigsmartsta bigsmartsta 14 hours ago Flag

    Cash

    The longer it takes to reach the hospitalization number, the better for CLDN. For example, if ZERO MYDICAR patients are rehospitalized by early 2015, then it could take years to reach that number if CUPID is not halted by the monitors before that due to outstanding efficacy. I would be happy to see the BREAKTHROUGH THERAPY designation still there and no news into May 2015. CLDN would be a loud-screaming BUY if that happened.

  • At the current illiquidity, the institutions can not buy.

  • The Class 3 and Ambulatory class 4 is HUMONGOUS. BOTH could prosper.

  • Every month that MYDICAR remains with the BREAKTHROUGH THERAPY designation, the distance between it and existing therapies continues to increase. There is a clear view of the finish-line.

  • Remember that BREAKTHROUGH Designation clearly sends the message that at this point in time, MYDICAR is setting RECORD EFFICACY for SURVIVAL with a very LOW MORBIDITY profile:

    Note the FDA definition of BREAKTHROUGH THERAPY includes the words "SUBSTANTIAL Improvement over available therapies." A very important sentence fragment. See below:

    "As defined by FDA, breakthrough product designation is intended for products that treat a serious condition based on preliminary clinical evidence that indicates the drug may demonstrate substantial improvement on clinically significant endpoints over available therapies."

  • bigsmartsta bigsmartsta Jul 27, 2014 5:09 PM Flag

    I happen to be long SSH and CLDN. The POTENTIAL is HUGE.

  • bigsmartsta bigsmartsta Jul 27, 2014 3:20 PM Flag

    To emphasis my conclusion again that EXCLUDING DHF, sharply increased the probability of SUCCESS for CLDN's CUPID trial see the paper's conclusion below again:

    "Although there has been considerable progress in the management of SHF, the management of DHF remains mostly EMPIRICAL because of LACK OF NOWLEDGE of the molecular and biochemical mechanisms which produce myocardial structural and functional changes in this syndrome. Further research and investigations are URGENTLY REQUIRED

  • 1- The main question of why would CLDN choose a clinical trial of just Systolic patients and why would SSH choose a clinical trial using BOTH Diastolic AND Systolic.

    2- The answer lies in the 'Conclusion' section of the following COPY PASTE:

    "Background: Diastolic heart failure (DHF) and systolic heart failure (SHF) are 2 clinical subsets of the
    syndrome of chronic heart failure that are most commonly encountered in clinical practice.

    Methods and Results: The clinically overt DHF and SHF appear to be 2 separate syndromes with distinctive morphologic and functional changes although signs, symptoms, and prognosis are very similar. In DHF, the left ventricle is not dilated and the ejection fraction is preserved. In contrast in SHF, it is dilated and the ejection fraction is reduced. The neurohormonal abnormalities in DHF and SHF appear to be similar. The stimuli and the signals that ultimately produce these 2 different phenotypes of chronic heart failure remain, presently, largely unknown.

    Conclusions: Although there has been considerable progress in the management of SHF, the management of DHF remains mostly empirical because of lack of knowledge of the molecular and biochemical mechanisms which produce myocardial structural and functional changes in this syndrome. Further research and investigations are urgently required. (J Cardiac Fail 2007;13:569e576)

    3- Since there is much more that is known in the treatment & management of SHF, CLDN INCREASED the probability of a SUCCESSFUL clinical trial by ONLY concentrating on SHF, and then after starting a clinical trial of DHF. Since SHF population is HUGE anyway, why not reduce the risk of failure with a largely unknown treatment path by separating the two.

    4- My belief is that SSH opted for an accelerated enrollment by including enrollment in BOTH sets of patients. But this increases the risk of failure

  • bigsmartsta bigsmartsta Jul 27, 2014 10:10 AM Flag

    To reemphasis my conclusion that excluding DHF, sharply increased the probability of SUCCESS for CLDN's CUPID trial see the paper's conclusion below again:

    "Although there has been considerable progress in the management of SHF, the management of DHF remains mostly EMPIRICAL because of LACK OF NOWLEDGE of the molecular and biochemical mechanisms which produce myocardial structural and functional changes in this syndrome. Further research and investigations are URGENTLY REQUIRED.

  • 1- The question is why would CLDN choose a clinical trial of just Systolic patients and why would SSH choose a clinical trial using BOTH Diastolic AND Systolic.

    2- The answer lies in the 'Conclusion' section of the following COPY PASTE:

    "Background: Diastolic heart failure (DHF) and systolic heart failure (SHF) are 2 clinical subsets of the
    syndrome of chronic heart failure that are most commonly encountered in clinical practice.
    Methods and Results: The clinically overt DHF and SHF appear to be 2 separate syndromes with
    distinctive morphologic and functional changes although signs, symptoms, and prognosis are very similar.
    In DHF, the left ventricle is not dilated and the ejection fraction is preserved. In contrast in SHF, it is
    dilated and the ejection fraction is reduced. The neurohormonal abnormalities in DHF and SHF appear
    to be similar. The stimuli and the signals that ultimately produce these 2 different phenotypes of chronic
    heart failure remain, presently, largely unknown.

    Conclusions: Although there has been considerable progress in the management of SHF, the management
    of DHF remains mostly empirical because of lack of knowledge of the molecular and biochemical mechanisms
    which produce myocardial structural and functional changes in this syndrome. Further research
    and investigations are urgently required. (J Cardiac Fail 2007;13:569e576)

    3- Since there is much more that is known in the treatment & management of SHF, CLDN INCREASED the probability of a SUCCESSFUL clinical trial by ONLY concentrating on SHF, and then after starting a clinical trial of DHF. Since SHF population is HUGE anyway, why not reduce the risk of failure with a largely unknown treatment path by separating the two.

    4- My belief is that SSH opted for an accelerated enrollment by including enrollment in BOTH sets of patients. But this increases the risk of failure.

  • The true incidence and prevalence of primary diastolic heart failure is difficult to estimate, as most studies are not prospective and have been performed in referral institutions. In the Study of LV Dysfunction (SOLVD) registry, approximately 30% of patients with the diagnosis of heart failure had preserved LV systolic function.[15-19] In a number of retrospective studies, the reported incidence of diastolic heart failure varied between 20%-40%.[15] The community studies reported an incidence as high as 50%.[18] In all studies, however, it has been observed that the incidence increases with age. In patients less than 60 years old, the incidence is about 15%-25%; between 60-70 years old, it is 35%-40%; and in patients 70 years old or older, approximately a 50% incidence of diastolic heart failure has been observed. The incidence is also higher in elderly women. The reasons for a higher incidence in females than in males are not entirely clear. Why primary diastolic failure is more common in the elderly is also not clear. Age-related changes in the myocardial structure and function and changes in the neuroendocrine profile have been suggested as contributing factors.[20]

  • In animal studies, it has been observed that myocardial cell size increases with age. The collagen content of the myocardium also increases. The sarcoplasmic reticular calcium ATPase activity (SERCA), which is necessary for appropriate calcium reuptake and initiation of myocardial relaxation, has been found to be DECREASED in senescent hearts. The overexpression of SERCA in senescent hearts in transgenic animals has been shown to ENHANCE myocardial relaxation and contractile function.

  • Since there are so many other variables such as blood pressure, organ dysfunction, angina, etc., one methodology may not fit all and therefore both the C-Pulse and MYDICAR will share the MULTI-$$$BILLIONS.

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