The Phase2 trial will have limitations due to its
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Posted On: 02/07/2021 4:25:26 PM
The Phase2 trial will have limitations due to its size. We can expect the phase 3 trial to be much larger and more statistically accurate.
One undeniable factor in Brilacidin's favor is how mediocre the Covid19 antiviral competitors have been. Below is listed some of the concerns with Remdesivir, Regeneron's antibody therapy and Bamlanivimab.
Remdesivir is the Covid19 antiviral of choice at many hospitals in spite of its widely criticized early trial.Its "adaptive trial" was changed in mid course when it became obvious it did not improve mortality. Its only treatment benefit was a shorter hospital stay which was not an initial end point of the trial.The control group was eliminated.
"The study found that on day 11, patients in the five-day remdesivir arm were 65% more likely to achieve better clinical scores than the standard care arm. Using the same yardstick, there was no benefit with 10 days of remdesivir. Also, there was no reduction in hospitalisation, mortality or reduced duration of oxygen requirement. They concluded that patients receiving five days of remdesivir had a significantly different clinical status than those receiving standard therapy, with uncertain clinical importance.
As with previous COVID-19 related clinical trials, there are several red flags we need to address before interpreting the results. Of note: the sponsor of the trial is Gilead Sciences Inc., a major manufacturer of remdesivir. Additionally, the end-point is an unimpressive one: odds of a better clinical status is quite vague relative to other, more clinically meaningful measurements like mortality, hospital stay, duration of oxygen requirement, etc. None of the authors’ own exploratory end-points, such as time to recovery or time to improvement in clinical status (by 1, 2 or 3 points) were significantly different with remdesivir.
Of the patients included, 80-85% had a clinical score of 5 (hospitalised, not requiring supplemental oxygen but requiring ongoing medical care). It is unclear how the same end-point – change in clinical status – that was used by the trial group for their previous trials involving severe COVID-19 patients can be applied to patients with moderate disease.
At the outset, the premise of this trial is questionable at the least. Remdesivir costs Rs 5,000 per dose, implying a cost of Rs 30,000 or Rs 60,000 for a five- or 10-day course respectively. In people with moderate COVID-19, where the mortality was 1%, it is impossible to justify remdesivir’s use without evidence of concrete clinical benefit. There is nothing objectionable about negative trials – which are those trials that fail to achieve their desired end-point. However, the fact that this trial was allowed to report its result as positive, in favour of remdesivir, is highly suspect.
Also read: Remdesivir – a Drug in Search of a Disease
In a nutshell, this trial encapsulates the issues with trials funded by the pharmaceutical industry in the context of the COVID-19 pandemic. By applying an ambiguous end-point to a patient population that may not have needed any treatment other than supportive care or supplemental oxygen, this trial bears all the hallmarks of bad science. Another difficult concept to grasp is why patients receiving 10 days of remdesivir had no difference in clinical status compared to standard treatment, while those receiving five days of treatment did. Considering that all three arms had comparable characteristics and were randomised, the benefit from remdesivir should have been apparent in both arms, not just one.
By consistently allowing poorly designed trials to make their way in to prestigious journals – JAMA is the third highest rated medicine journal in the world – the medical fraternity is doing itself a great disservice. Research can only be considered reliable when it is scientifically sound and can withstand the scrutiny of rigorous peer review. Once trust in science is eroded, the after effects will be felt long after the pandemic has abated."
https://science.thewire.in/the-sciences/remde...d-science/
https://jamanetwork.com/journals/jama/fullarticle/2769870
https://jamanetwork.com/journals/jama/fullarticle/2768397
Regeneron's antibody treatment is still under review. Regeneron has tightly controlled the little data that has been released. Regeneron claims treatment given early can reduce the viral load and reduce "medically supervised visits". I can find no data on mortality, complications, reduced ventilator or oxygen usage.
The best summary I could find of the data is below describing both Regeneron's antibody and Lily's Bamlanivimab.
".. the monoclonal antibody products I'll be discussing have had studies that have not shown benefit or have been associated with worse outcomes for hospitalized patients, especially those on high-flow oxygen or in the intensive care unit (ICU)."
"This kind of strategy for early treatment is going to be a minor contribution from a prevention standpoint before we have widespread, effective vaccines. Studies remain in progress where it might have a larger role (although a very expensive one) in preventing disease in patients who might be at [higher] risk — especially, for example, in congregate living facilities or nursing facilities. Unfortunately, we will need to wait for data to see if this is effective.
So, we have some newer therapies. Nothing is a home run... "
https://www.medscape.com/viewarticle/941830
New data released suggested a use for monoclonal antibodies and Remdesivir for preventative care.
https://www.medscape.com/viewarticle/945136#vp_2
GLTA Farrell
One undeniable factor in Brilacidin's favor is how mediocre the Covid19 antiviral competitors have been. Below is listed some of the concerns with Remdesivir, Regeneron's antibody therapy and Bamlanivimab.
Remdesivir is the Covid19 antiviral of choice at many hospitals in spite of its widely criticized early trial.Its "adaptive trial" was changed in mid course when it became obvious it did not improve mortality. Its only treatment benefit was a shorter hospital stay which was not an initial end point of the trial.The control group was eliminated.
"The study found that on day 11, patients in the five-day remdesivir arm were 65% more likely to achieve better clinical scores than the standard care arm. Using the same yardstick, there was no benefit with 10 days of remdesivir. Also, there was no reduction in hospitalisation, mortality or reduced duration of oxygen requirement. They concluded that patients receiving five days of remdesivir had a significantly different clinical status than those receiving standard therapy, with uncertain clinical importance.
As with previous COVID-19 related clinical trials, there are several red flags we need to address before interpreting the results. Of note: the sponsor of the trial is Gilead Sciences Inc., a major manufacturer of remdesivir. Additionally, the end-point is an unimpressive one: odds of a better clinical status is quite vague relative to other, more clinically meaningful measurements like mortality, hospital stay, duration of oxygen requirement, etc. None of the authors’ own exploratory end-points, such as time to recovery or time to improvement in clinical status (by 1, 2 or 3 points) were significantly different with remdesivir.
Of the patients included, 80-85% had a clinical score of 5 (hospitalised, not requiring supplemental oxygen but requiring ongoing medical care). It is unclear how the same end-point – change in clinical status – that was used by the trial group for their previous trials involving severe COVID-19 patients can be applied to patients with moderate disease.
At the outset, the premise of this trial is questionable at the least. Remdesivir costs Rs 5,000 per dose, implying a cost of Rs 30,000 or Rs 60,000 for a five- or 10-day course respectively. In people with moderate COVID-19, where the mortality was 1%, it is impossible to justify remdesivir’s use without evidence of concrete clinical benefit. There is nothing objectionable about negative trials – which are those trials that fail to achieve their desired end-point. However, the fact that this trial was allowed to report its result as positive, in favour of remdesivir, is highly suspect.
Also read: Remdesivir – a Drug in Search of a Disease
In a nutshell, this trial encapsulates the issues with trials funded by the pharmaceutical industry in the context of the COVID-19 pandemic. By applying an ambiguous end-point to a patient population that may not have needed any treatment other than supportive care or supplemental oxygen, this trial bears all the hallmarks of bad science. Another difficult concept to grasp is why patients receiving 10 days of remdesivir had no difference in clinical status compared to standard treatment, while those receiving five days of treatment did. Considering that all three arms had comparable characteristics and were randomised, the benefit from remdesivir should have been apparent in both arms, not just one.
By consistently allowing poorly designed trials to make their way in to prestigious journals – JAMA is the third highest rated medicine journal in the world – the medical fraternity is doing itself a great disservice. Research can only be considered reliable when it is scientifically sound and can withstand the scrutiny of rigorous peer review. Once trust in science is eroded, the after effects will be felt long after the pandemic has abated."
https://science.thewire.in/the-sciences/remde...d-science/
https://jamanetwork.com/journals/jama/fullarticle/2769870
https://jamanetwork.com/journals/jama/fullarticle/2768397
Regeneron's antibody treatment is still under review. Regeneron has tightly controlled the little data that has been released. Regeneron claims treatment given early can reduce the viral load and reduce "medically supervised visits". I can find no data on mortality, complications, reduced ventilator or oxygen usage.
The best summary I could find of the data is below describing both Regeneron's antibody and Lily's Bamlanivimab.
".. the monoclonal antibody products I'll be discussing have had studies that have not shown benefit or have been associated with worse outcomes for hospitalized patients, especially those on high-flow oxygen or in the intensive care unit (ICU)."
"This kind of strategy for early treatment is going to be a minor contribution from a prevention standpoint before we have widespread, effective vaccines. Studies remain in progress where it might have a larger role (although a very expensive one) in preventing disease in patients who might be at [higher] risk — especially, for example, in congregate living facilities or nursing facilities. Unfortunately, we will need to wait for data to see if this is effective.
So, we have some newer therapies. Nothing is a home run... "
https://www.medscape.com/viewarticle/941830
New data released suggested a use for monoclonal antibodies and Remdesivir for preventative care.
https://www.medscape.com/viewarticle/945136#vp_2
GLTA Farrell
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