From Frank on YMB provided good summary on how the FDA evaluates potential candidates for approval.
Everybody who has at least some limited knowledge and experience on how the FDA, the EMA (European Medicine Agency), the British or other drug authorities assess medicines know how at the end the decision is made:
it is based on a RISK (possible side effects) versus (clinical) BENFIT analysis. And this assessment takes also into account the risk-benefit of existing drugs against the disease and the disease itself. For example: if there is no or little effective treatment against a certain cancer: then a drug which offers some benefit may also be accepted despite severe side effects (as we all know for most of the anti- cancer drugs). If there is already an effective drug with little side effects, then a new drug should not have a worse risk (= side effects) - benefit (=efficacy) profile.
Now leronlimab:
1) Safety first: we have more than 800 patients from the phase III HIV trial, plus the perfect safety from the M&M trial. And also the DSMC review on the ongoing S/C phase 2b/3 (phase III !) Trial confirmed: zero safety issue for leronlimab. Cannot be any better.
2) Now the second element: efficacy:
In the M/M trial we had less than half of the adverse events of the placebo group - statistically significant (p< 0.05) Placebo is water, inert without any effect. Now if anything is reducing adverse events by more than half that means that it must have an effect, by either strengthening the immune system or any other effect that is strengthening the overall health to make the body more resistent to adverse events (adverse events include also events caused by the virus, e.g. required ventilation, cardiac failure, kidney failure, thrombosis, stroke....). It is true: normally this endpoint „adverse events“ are put to the safety section of the dossier, BUT: normally „adverse events“ are never reduced by drug“ (rather increased by the drugs side effects). That is why it is normally in section“safety“. Somebody said in more than 300 trials he had conducted he never saw such reduction. I did not conduct any clinical trial, but I have assessed an even higher number of clinical trials for the drug authority of an European Member State and the European Medicine Agency. I also cannot recall any such result. The only logic explanation is that the drug is efficient. It works. Other elements for the efficacy assessment: ideally also one or another endpoint (primary or secondary does not matter here in Covid - see Remdesivir approval) is positive or at least show non-statistically improved or better figures as compared to placebo. A lot of scientific weight is also given to the mode of action. Is it plausible? Has it been shown (changes in cytokines, T-helper cells, viral load in the blood? - Ideally in those patients which shown also clinical improvement. That would be also strong evidence for the efficacy of a new drug. I am confident that this is shown for leronlimab.
And finally the 54 IND patients from the uncontrolled trial will also be considered. Alone it would not be enough - but such data is usually considered „supportive“.
At the end the FDA, EMA, the British and other authorities will do this risk-benefit analysis. Risk of leronlimab is almost if not totally zero. For the benefit we have some strong evidence from the clinical trials supported by a reasonable mode of action and the 54 IND patients.
The last step is then the FDA and other drug authorities will compare that with the approved therapies: we have very little here:
Remdesivir: Little if any effect on a minor secondary endpoint, and side effects on liver and kidney. Theoretical mode of action (antiviral) but could not reduce viral load in COVID patients.
Dexamethason (strong cortison with all the side effect of cortison including immunosupression. We do not need an „Atombombe“ immunosupression here, we need a targeted effect on the immune system to calm the devastating cytokine storm.
FDA, EMA etc will consider all the above in much more detailed way, but eventually there is only one outcome here: approval of leronlimab.
BTW: the same applies for HIV where we even have the full phase III data (non-pandemie Standard). Leronlimab is by far better than all other current anti-HIV drugs. It will be the new standard. Now you know why I invest in leronlimab (CYDY).
Everybody who has at least some limited knowledge and experience on how the FDA, the EMA (European Medicine Agency), the British or other drug authorities assess medicines know how at the end the decision is made:
it is based on a RISK (possible side effects) versus (clinical) BENFIT analysis. And this assessment takes also into account the risk-benefit of existing drugs against the disease and the disease itself. For example: if there is no or little effective treatment against a certain cancer: then a drug which offers some benefit may also be accepted despite severe side effects (as we all know for most of the anti- cancer drugs). If there is already an effective drug with little side effects, then a new drug should not have a worse risk (= side effects) - benefit (=efficacy) profile.
Now leronlimab:
1) Safety first: we have more than 800 patients from the phase III HIV trial, plus the perfect safety from the M&M trial. And also the DSMC review on the ongoing S/C phase 2b/3 (phase III !) Trial confirmed: zero safety issue for leronlimab. Cannot be any better.
2) Now the second element: efficacy:
In the M/M trial we had less than half of the adverse events of the placebo group - statistically significant (p< 0.05) Placebo is water, inert without any effect. Now if anything is reducing adverse events by more than half that means that it must have an effect, by either strengthening the immune system or any other effect that is strengthening the overall health to make the body more resistent to adverse events (adverse events include also events caused by the virus, e.g. required ventilation, cardiac failure, kidney failure, thrombosis, stroke....). It is true: normally this endpoint „adverse events“ are put to the safety section of the dossier, BUT: normally „adverse events“ are never reduced by drug“ (rather increased by the drugs side effects). That is why it is normally in section“safety“. Somebody said in more than 300 trials he had conducted he never saw such reduction. I did not conduct any clinical trial, but I have assessed an even higher number of clinical trials for the drug authority of an European Member State and the European Medicine Agency. I also cannot recall any such result. The only logic explanation is that the drug is efficient. It works. Other elements for the efficacy assessment: ideally also one or another endpoint (primary or secondary does not matter here in Covid - see Remdesivir approval) is positive or at least show non-statistically improved or better figures as compared to placebo. A lot of scientific weight is also given to the mode of action. Is it plausible? Has it been shown (changes in cytokines, T-helper cells, viral load in the blood? - Ideally in those patients which shown also clinical improvement. That would be also strong evidence for the efficacy of a new drug. I am confident that this is shown for leronlimab.
And finally the 54 IND patients from the uncontrolled trial will also be considered. Alone it would not be enough - but such data is usually considered „supportive“.
At the end the FDA, EMA, the British and other authorities will do this risk-benefit analysis. Risk of leronlimab is almost if not totally zero. For the benefit we have some strong evidence from the clinical trials supported by a reasonable mode of action and the 54 IND patients.
The last step is then the FDA and other drug authorities will compare that with the approved therapies: we have very little here:
Remdesivir: Little if any effect on a minor secondary endpoint, and side effects on liver and kidney. Theoretical mode of action (antiviral) but could not reduce viral load in COVID patients.
Dexamethason (strong cortison with all the side effect of cortison including immunosupression. We do not need an „Atombombe“ immunosupression here, we need a targeted effect on the immune system to calm the devastating cytokine storm.
FDA, EMA etc will consider all the above in much more detailed way, but eventually there is only one outcome here: approval of leronlimab.
BTW: the same applies for HIV where we even have the full phase III data (non-pandemie Standard). Leronlimab is by far better than all other current anti-HIV drugs. It will be the new standard. Now you know why I invest in leronlimab (CYDY).
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