Some early monoclonal antibody results - Printable Version
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Some early monoclonal antibody results - Goose - 09-16-2020
https://www.prnewswire.com/news-releases/lilly-announces-proof-of-concept-data-for-neutralizing-antibody-ly-cov555-in-the-covid-19-outpatient-setting-301131785.html
Still an early result (phase 2), but encouraging nevertheless. If we can keep people out of the hospital with this kind of treatment we can tolerate a higher case load, and fewer people will die.
RE: Some early monoclonal antibody results - akiddoc - 09-16-2020
(09-16-2020, 07:24 AM)Goose Wrote: https://www.prnewswire.com/news-releases/lilly-announces-proof-of-concept-data-for-neutralizing-antibody-ly-cov555-in-the-covid-19-outpatient-setting-301131785.html
Still an early result (phase 2), but encouraging nevertheless. If we can keep people out of the hospital with this kind of treatment we can tolerate a higher case load, and fewer people will die.
The cost of these drugs will likely make it impractical use them in mildly sick individuals. Side effects are sometimes severe with MOABS as well. Whether they will do much for you once you are really sick is to be determined.
RE: Some early monoclonal antibody results - dabigv13 - 09-16-2020
I share akkidoc's skepticism about these drugs. Hard to imagine they will play a big role in the management of the pandemic at large. Won't be used widely in mild cases, and once a case is severe, most of the damage at that point is done by the immune system not the virus.
In addition to cost, they are administered by IV, which will also limit widespread usage.
RE: Some early monoclonal antibody results - Goose - 09-16-2020
(09-16-2020, 07:00 PM)akiddoc Wrote:Interesting, because that seems to be the patient population they are looking at, people who are positive within the last three days but not really sick yet. Seems that wouldn't make sense if this drug was going to be real expensive for exactly the reason you cite. It wouldn't be given to people who were not in great need if the cost is high.(09-16-2020, 07:24 AM)Goose Wrote: https://www.prnewswire.com/news-releases/lilly-announces-proof-of-concept-data-for-neutralizing-antibody-ly-cov555-in-the-covid-19-outpatient-setting-301131785.html
Still an early result (phase 2), but encouraging nevertheless. If we can keep people out of the hospital with this kind of treatment we can tolerate a higher case load, and fewer people will die.
The cost of these drugs will likely make it impractical use them in mildly sick individuals.
Quote:Side effects are sometimes severe with MOABS as well.True, but they are saying that so far at least they have no treatment-related SAEs. We will obviously have more data at the end of the study.
Quote:Whether they will do much for you once you are really sick is to be determined.True, and this study isn't really targeting those individuals. This study is done on an outpatient basis, so you get the IV and go home. They are claiming pretty significant reductions in hospitalizations.
RE: Some early monoclonal antibody results - BostonCard - 09-17-2020
Quote:These biomarker data correlated with LY-CoV555's positive impact on the prespecified endpoint of COVID-19-related hospitalization or ER visit. This endpoint occurred in 1.7 percent (5/302) of LY-CoV555 patients, pooled across dose groups, as compared to 6 percent (9/150) of placebo patients, which corresponds to a 72 percent risk reduction in this limited population.
The numbers are small and the confidence interval is wide, but if you used the point estimate, you would need to treat 23 patients with COVID-19 to prevent one COVID-19-related hospitalization on ER visit. Whether it is worth it might depend on whether most of those are hospitalizations or ER visits.
BC
RE: Some early monoclonal antibody results - Goose - 09-17-2020
(09-17-2020, 09:57 AM)BostonCard Wrote:Indeed this is another example of the "relative benefit" making a treatment look more useful than it actually is. Since only 6% of the control group was hospitalized, you would need to treat a lot of people to have any real benefit (1 in 23). Obviously the ability to do that depends greatly on the cost of the therapy, which we don't know. It may be that a sub-fraction of the subjects benefited more significantly, like possibly the people over 50 years old. The phase 2 study probably isn't large enough for this kind of analysis, so we won't know for a while.Quote:These biomarker data correlated with LY-CoV555's positive impact on the prespecified endpoint of COVID-19-related hospitalization or ER visit. This endpoint occurred in 1.7 percent (5/302) of LY-CoV555 patients, pooled across dose groups, as compared to 6 percent (9/150) of placebo patients, which corresponds to a 72 percent risk reduction in this limited population.
The numbers are small and the confidence interval is wide, but if you used the point estimate, you would need to treat 23 patients with COVID-19 to prevent one COVID-19-related hospitalization on ER visit. Whether it is worth it might depend on whether most of those are hospitalizations or ER visits.
BC
I would also assume that there is a trial going on with patients that are already hospitalized. In those cases lowering the virus titers is only part of the story. The immune system response, secondary infections and a host of other things also become factors. That said, it is not unreasonable to expect that the ability to drive down the virus titers while still suppressing an over-active immune system would be very useful.
An obvious possibility for improvement in effectiveness would be obtained if the ability to predict who would require hospitalization was available. In the clinical trial this was not attempted. I am sure that in the "real world" there is some ability to do this, but in the absence of any real treatment being available it probably hasn't been a priority. If there is an effective treatment available even a modest improvement in predicting who should receive it would be a big force multiplier.
RE: Some early monoclonal antibody results - Goose - 10-14-2020
Somewhat of a glitch. Too soon to know the seriousness of the issue. Hopefully in the placebo group!
https://www.cnbc.com/2020/10/13/us-pauses-eli-lillys-trial-of-a-coronavirus-antibody-treatment-over-safety-concerns.html
RE: Some early monoclonal antibody results - dabigv13 - 10-14-2020
It sounded like the placebo group was doing better than the treatment group so they paused the study. Not ideal.
https://www.nytimes.com/2020/10/13/health/eli-lilly-antibody.html
RE: Some early monoclonal antibody results - BostonCard - 10-14-2020
Man, the communication on that is lousy. Based on the NY Times article, the company says that the trial was being halted "out of an abundance of caution" for a "potential safety concern", but if you look at the text, it really sounds like the study may have met the criteria for futility because patients who were getting the monoclonal antibody appeared to be doing worse than patients getting placebo, a difference that was large enough at this point in the clinical trial that continuing to enroll patients was "futile" because it was very unlikely that, conditional on the data observed by the DSMB to date, it would be highly unlikely that efficacy could be shown even if the trial was fully recruited. Obviously, if your drug is making patients worse, that is both a safety and efficacy issue, but unlike the problems that were being seen with vaccines, where a single patient had an unsual adverse event which might have been due to the vaccine, this looks to be based on an overall imbalance between the treated and placebo groups.
That being said, there was a recent case of a clinical trial in Alzheimer's disease that was halted early due to "futility", but then later the company sponsoring the trial (Biogen) claimed that after more data came in, that the drug actually worked and that they planned to file with the FDA. These claims are hard to evaluate because I don't think the data has been publicly released, but it could be a precedent here.
BC
RE: Some early monoclonal antibody results - dabigv13 - 10-14-2020
The Trump admin is pushing for EUA's for these meds already. The Regeneron one is not the Lilly one, but if this mAb is not helping, I would be surprised if Regeneron's is the "cure" that Trump is selling. And once an EUA comes, we may not know how effective the meds are since we won't be testing it in a controlled trial. Maybe overseas studies would still continue and give us some insight.
RE: Some early monoclonal antibody results - Goose - 10-14-2020
(10-14-2020, 09:30 AM)dabigv13 Wrote: The Trump admin is pushing for EUA's for these meds already. The Regeneron one is not the Lilly one, but if this mAb is not helping, I would be surprised if Regeneron's is the "cure" that Trump is selling. And once an EUA comes, we may not know how effective the meds are since we won't be testing it in a controlled trial. Maybe overseas studies would still continue and give us some insight.I would imagine the vendors will continue clinical trials because an EUA isn't an ideal way to receive compensation for a drug. Insurance companies want "approved" therapies. In some cases the EUA makes it hard to recruit patients because you don't have to be on a trial to get the treatment. In this case I think there are enough patients in the USA that won't be a problem. Could also be a problem if having a "placebo" group is considered unethical, but I would imagine a drug would have to truly and obviously be a "game changer" for that to happen.
RE: Some early monoclonal antibody results - dabigv13 - 10-14-2020
Remdesivir is still on an EUA. If one of the mAbs gets an EUA, I think it's unlikely they will be saving large numbers of doses for a study. Remember the government is already on the hook for a lot of money for these drugs.
RE: Some early monoclonal antibody results - BostonCard - 10-14-2020
(10-14-2020, 11:00 AM)Goose Wrote:(10-14-2020, 09:30 AM)dabigv13 Wrote: The Trump admin is pushing for EUA's for these meds already. The Regeneron one is not the Lilly one, but if this mAb is not helping, I would be surprised if Regeneron's is the "cure" that Trump is selling. And once an EUA comes, we may not know how effective the meds are since we won't be testing it in a controlled trial. Maybe overseas studies would still continue and give us some insight.I would imagine the vendors will continue clinical trials because an EUA isn't an ideal way to receive compensation for a drug. Insurance companies want "approved" therapies. In some cases the EUA makes it hard to recruit patients because you don't have to be on a trial to get the treatment. In this case I think there are enough patients in the USA that won't be a problem. Could also be a problem if having a "placebo" group is considered unethical, but I would imagine a drug would have to truly and obviously be a "game changer" for that to happen.
The issue isn't what the Sponsor wants to do; it is what patients want to do once EUA is available. Given a choice between a clinical trial with a 50/50 (or, at best, a 2:1 odds) of getting the active drug or knowing you are getting the active treatment under an EUA, most patients will elect to get the treatment. The issue is if there is limited availability of the treatment through the EUA, and the choice facing the patient is a clinical trial or nothing.
BC
There is some precedence of monoclonal antibodies failing in clinical trials of respiratory diseases:
https://aac.asm.org/content/64/7/e00352-20
(disclosure: I am one of the authors on that paper)
BC
RE: Some early monoclonal antibody results - DenverCard - 10-14-2020
The doubts about the effectiveness of monoclonal antibodies leaves me all the more perplexed by the clinical course of Donald Trump's infection. As best as I know/remember, he reportedly deteriorated rapidly a Friday morning. Given his risk factors -- age, sex, weight, terrible diet -- I expected he would have a rather tough time. Yet he very quickly improved and was discharged Monday. That evening, he looked out of breath after climbing a flight of stairs, but soon thereafter he looked back to baseline.
I was ready to give the credit to his recovery to the prompt treatment with the monoclonal antibodies that he received, given that Remdesivir's impact has generally not been dramatic, and given that it seemed too early for dexamethasone to have a large effect. So now I'm left wondering how best to account for his outcome. I guess any of the three interventions could be game changers for any particular individual. Perhaps the combination is synergistic. Perhaps he would have had the same clinical course without treatment. Such a crapshoot.
RE: Some early monoclonal antibody results - dabigv13 - 10-14-2020
The study that has been paused was for hospitalized patients getting remdesivir as well, so it's possible that is too late in the disease process for the mAbs to be effective.
Trump's clinical condition has so many open questions and is an n of 1. And even as an old, obese man, a mild case is still more likely than a severe one.
RE: Some early monoclonal antibody results - BostonCard - 10-14-2020
(10-14-2020, 12:32 PM)DenverCard Wrote: The doubts about the effectiveness of monoclonal antibodies leaves me all the more perplexed by the clinical course of Donald Trump's infection. As best as I know/remember, he reportedly deteriorated rapidly a Friday morning. Given his risk factors -- age, sex, weight, terrible diet -- I expected he would have a rather tough time. Yet he very quickly improved and was discharged Monday. That evening, he looked out of breath after climbing a flight of stairs, but soon thereafter he looked back to baseline.
I was ready to give the credit to his recovery to the prompt treatment with the monoclonal antibodies that he received, given that Remdesivir's impact has generally not been dramatic, and given that it seemed too early for dexamethasone to have a large effect. So now I'm left wondering how best to account for his outcome. I guess any of the three interventions could be game changers for any particular individual. Perhaps the combination is synergistic. Perhaps he would have had the same clinical course without treatment. Such a crapshoot.
A three night hospitalization is well within what might be expected for a patient with COVID-19 (even one with multiple risk factors) who doesn't require ICU care or mechanical ventilation.
BC
RE: Some early monoclonal antibody results - Goose - 10-14-2020
(10-14-2020, 11:05 AM)BostonCard Wrote:True about patient preferences if they can get access through the EUA. Doesn't it depend on what the EUA actually allows. If you can only use it in an "Emergency", it would seem that people who are not yet in serious/critical condition (and not predisposed to get that way) wouldn't qualify. I am assuming it works that way, at least in theory. A clinical trial could chose people who are sick but not in a life-or-death situation and still recruit OK.(10-14-2020, 11:00 AM)Goose Wrote: I would imagine the vendors will continue clinical trials because an EUA isn't an ideal way to receive compensation for a drug. Insurance companies want "approved" therapies. In some cases the EUA makes it hard to recruit patients because you don't have to be on a trial to get the treatment. In this case I think there are enough patients in the USA that won't be a problem. Could also be a problem if having a "placebo" group is considered unethical, but I would imagine a drug would have to truly and obviously be a "game changer" for that to happen.
The issue isn't what the Sponsor wants to do; it is what patients want to do once EUA is available. Given a choice between a clinical trial with a 50/50 (or, at best, a 2:1 odds) of getting the active drug or knowing you are getting the active treatment under an EUA, most patients will elect to get the treatment. The issue is if there is limited availability of the treatment through the EUA, and the choice facing the patient is a clinical trial or nothing.
BC
RE: Some early monoclonal antibody results - BostonCard - 10-14-2020
The "emergency" in this case represents the pandemic. As soon as the pandemic declaration is over, the EUAs will expire.
https://en.wikipedia.org/wiki/Emergency_use_authorization
Quote:EUAs end once the Secretary of Heath and Human Services determines that the precipitating emergency has ended (in consultation with the issuer of the appropriate state of emergency as necessary), or once the product or unapproved use is approved through normal channels.[1]
The EUA carries specific language about the patient population; here's the EUA for remdisivir:
https://www.fda.gov/news-events/press-announcements/covid-19-update-fda-broadens-emergency-use-authorization-veklury-remdesivir-include-all-hospitalized
Quote:Today, as part of its ongoing efforts to fight COVID-19, the U.S. Food and Drug Administration broadened the scope of the existing emergency use authorization (EUA) for the drug Veklury (remdesivir) to include treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19, irrespective of their severity of disease.
We will see what the language for monoclonal antibodies says.
BC
RE: Some early monoclonal antibody results - dabigv13 - 10-15-2020
https://www.nytimes.com/2020/10/15/us/politics/chris-christie-face-masks-covid.amp.html
Chris Christie received the Lilly antibody as compassionate use. That antibody trial is currently on hold, possibly for futility, so unclear if it did him much good.
RE: Some early monoclonal antibody results - Goose - 12-18-2020
While these treatments are out there, they haven't been used as much as expected. Probably hard to know how much good they are doing without more numbers. The drugs cost 1.2K per patient, which is not nothing, but if it keeps people out of the hospital it would be a win.
https://www.reuters.com/article/us-health-coronavirus-treatments-antibod/u-s-hospitals-try-mab-squads-infusion-sites-to-boost-use-of-covid-19-antibody-drugs-idUSKBN28Q2WW