Pfizer new antiviral

well welcome to today's talk it's sunday evening the 7th of november now i don't want to be melodramatic because i get told off for that but this this one really is a potential game changer because this new anti-viral medication from pfizer they are claiming at the moment that there's an 89 reduction in hospitalizations and a 89 reduction in deaths so that means if this was rolled out globally if it's affordable if it's affordable this could be a massive massive thing all over the world really really could so um we'll be looking at this now this is the paper here well it's a press release actually now i've put the link in of course if you want to read it it is actually fairly uh intelligible um it took me about sort of maybe two two two and a half hours to uh to work out what it was uh what it was getting at all together so quite quite uh quite accessible really but of course it's science by press release which of course we're not that keen on but anyway let's just give a quick bit of background before we look at the detail on this new uh antiviral now uh protection from hospitalization the story so far so what these are these are all medications basically they would be given as soon as someone becomes symptomatic and they will be given to prevent people from deteriorating and needing hospitalization and therefore hopefully preventing severe illness and preventing death so that's a really good idea of course so that's what it's about now malnour pirovia has already been approved by the the hmra the regulatory authorities uh the medicine healthcare products regulatory agency in the uk and the government were refusive about how brilliant this is um the anti-virals found to be safe and effective following a stringent review of available evidence that they are saying in this direct government paper public domain data though which concerns me we have a merc press release from the company that's making it that's all we have and to me that is not enough because there are theoretical reasons why this drug could have side effects and we need peer-reviewed we need all the world scientists to peer-review this data before we are so effusive in our pro certainly on this channel as well as that it's 700 for a five-day course at least that's the price in the usa the uk price of course we don't know we haven't been told and it's just under a 50 reduction in uh i think i've spent that wrong in deterioration okay so it prevents about 50 people going to hospital which of course is is great so that's that one but um as we say waiting for peer review data because um you know we're dealing with a basically a new drug here um that there are reasons why it could cause problems um merck and the government are saying it doesn't but we want the world scientists to agree with them first before we go head over heels with that one this one on the other hand fluvoxamine that we looked at a few days ago this is part of the together trial public domed main data here is a peer-reviewed trial in the lancet which of course is much more a power street links there adults with a risk factor so uh age heart disease renal disease immunocompromise uh that they were given that as soon as soon after symptoms developed as possible this is four dollars for a course so not seven hundred four dollars for a course 32 protection against hospitalization 32 protection against death it's approved by the food and drug administration and the authorities in the uk and around about the world as an anti-depressant of course it's one of the selective serotonin you're taking inhibitor antidepressants so doctors already seem to be prescribing it off label using their clinical judgment according to that article there at least in the in the states and um given that uh fluvoxamine is is a as a known drug with a known safety profile i would be more than happy to take a 10-day course of it uh without too much hesitation so so that's that one um the next the next one that we've talked about on this channel is ivamectin now ivamectin is actually part of the together trial the together trials actually said ivormectin is not affected but they haven't released any data yet so i'm not going to risk talking about that further at the moment we'll wait and see what their data says although on this channel we have looked at data let's just say we've looked at data on either mectin before but we'll leave that there for now so this is the new trial here pfizer's novel covered 19 aural now this is the key thing these all these medicines that i've talked about here are all oral so the the flu voxamine is all the mole new piravir is oral you just take a tablet you don't have to go into hospital or a special facility as you do with a monoclonal antibodies which we know are affected but they have to be given intravenously so these could be given to anyone who's considered at high risk of deteriorating or being hospitalized or dying basically as soon as they get symptoms and it looks like the sooner after symptom onset they get these medications the better but more detail on that in a minute so this is their candidate reduced risk of hospitalizations or death by 89 i mean this is just wow this is a blow your socks off number way way better than you apparently yeah way way better than uh the the flu vox for flu voxamine although we don't know how much it's going to cost yet so we'll just put a question mark on that how much is fires are going to charge um my suspicion is it will not be cheap but we will see we might be pleasantly surprised public domain data so far fires a press release well that's it um that's all we've got at the moment so this is this is what we've got at the moment um but i think we can assume that what's in it is is valid they're not going to make things up in a press release uh pax lovid i guess that says pax lovid now this is the experimental name of the drug now it's called retinovir here now this confuses me because pfizer is saying this is a completely new drug but retinovir is an anti-retroviral drug that we've been using for hiv for years so is is this retinovir or is it a different molecule i think it's a slightly different molecule that must have jiggled around with it a bit so i guess it's based on retinovir but that's the experimental name of the drug and it's now called it's now called uh pax pax love it that's the trademark for it found to reduce the risk of hospitalization death by 89 direct quote compared to placebo in non-hospitalized but high-risk adults with covered 19 so again much in the same way as they did with the mole new peruvia trial they've taken patients who are at risk of deteriorating and they've followed them through so the follow through here is through to 28 days now headline here uh pax lovely group no deaths placebo group 10 deaths well that would be more than an 89 difference wouldn't it but but that's that's what they're saying here uh fizer plans to submit data for regulatory authorization asap of course and this is going to be everywhere so this press release doesn't say this it talks about the us fda but i think we can assume that pfizer have applied for licensing agreements everywhere at least everywhere that can afford to pay for it so it's phase two three epic hr so evaluation of protease inhibition that so this is this is a protease inhibitor for covid19 and heart in high-risk patients so that's the name of the trial so it's a protease inhibitor now i first use pr i've been trying to think about this i'm pretty sure that i first used protease inhibitors way back in 96 in in in india um as an antiretroviral treatment i think they came out in 95 protease inhibitors so what protease inhibitors do is to make a new virus the virus needs uh proteins particular proteins of particular proteins and to break long proteins up into shorter proteins it uses uh proteases enzymes that break down proteins so these drugs are protease inhibitors so that the the drugs the protease and hip inhibitors are inhibiting the proteases so the proteases can't chop the proteins up into the right length so you end up with proteins that are too long to be able to make the virus so the basic building blocks for the virus are denied at the virus that's that's how these things work protease inhibitors yeah and and yeah i'm pretty sure it was 1996 i first used these so so that is that is um that is pretty good safety profile so i actually feel much more comfortable about this personally uh because we've been using it for all these years rather than mold new piravir which is not been um extensively used before this this is a familiar if it's not an exact molecule it's a familiar group of drugs just like through vaccine it is a familiar group in the selective serotonin reuptake inhibitor category that i've taken myself and many others have taken so this this anyway but getting back to the pfizer study randomized double blind study of non-hospitalized patients adult patients with covered 19 high risk of progressing to severe illness now this is what you call a scheduled interim analysis so like halfway through the trial up yeah a bit more than halfway through this they stop and say well how are we getting on here if it's killing people that would stop the trial if it's curing people that would stop the trial because it would be unethical to continue 89 reduction in the risk of covered not in opposite dos from any cause compared to placebo so very efficacious and as a result of that as we'll see the trial was actually stopped because it because given that people were dying who received the placebo and people were living who received the uh pax love it it would be unethical to continue giving people a placebo um now more specifically in patients treated within three days of symptom onset so within three days of symptom onset uh in in the pax lovid group so this is the paxologic group here um 0.8 of patients were hospitalized three out of 389 patients no deaths so that's one group there here's the placebo group to compare it to uh so there's the placebo group because we like to compare groups with groups is exactly what we do there's the placebo group seven percent of what patients hospitalized that was 27 out of 385 tragically seven uh subsequent deaths and the probability that the difference between the paxlovid group and the placebo group arose by chance was p equals 0.0001 which is a one in ten thousand chance that that result could arise by chance in other words we're pretty certain that this is a genuine difference between the two groups greatly in favor of the pak slovad group i mean that is a clear cut slam dunk as far as clinical trials are concerned it doesn't get much clearer than that so it's looking it's looking remarkably uh amazing really at the moment in patients treated within five days of symptoms uh one percent of patients in the pax lobby group were hospitalized six out of 607 so clearly well not clearly but this is intimating quite strongly that the earlier the treatment started the better placebo group it was a 6.7 percent of patients hospitalized or died for 21 out of the 612 10 subsequent deaths i'm afraid and again the the p value one in 10 000 that this result arose by chance so again we've got the comparison between the two groups there and it's clear this is what clinical trials are all about comparing the placebo group with the intervention group and the result is clear so at the recommendation of the independent data monitoring committee and in consultation with the us food and drug administration the fires that will cease uh continued enrollment so basically the data monitoring committee which is independent and genuinely independent uh no cynicism there at all uh and the fda at us that they said no we're happy with this you don't need to carry on experimenting this data is good enough and given the numbers we've got on those p values it is good enough i agree completely in fact it's really quite impressive due to overwhelming efficacy of the results demonstrated um now that got as far as enrolling 1219 adults they were scheduled to do three thousand now if the results had been more subtle if they'd been more subtle you might have needed 3 000 to differentiate if there was a benefit or if there was a adverse effect but the the effect is so obviously massively beneficial that 1219 patients were more than enough more than enough um these patients uh were recruited in north and south america quite a few from the united states actually europe africa and asia so international cohorts which is always good to see enrolled individuals all had a deborah confirmed diagnosis of um pcr diagnosis confirmed they were all definitely infected they all had early moderate mild to moderate symptoms which of course virtually everyone does at the beginning so this listen is not really excluding many people which is exactly what we want of course and they had at least one underlying comorbidity or increased age randomized one-to-one or placebo or really every 12 hours for five days so as simple as taking a pill which is what it is now safety this is crucial now with the mullen or peruvia there is a reason and i don't know yet i stress i don't know and i stress that the regulatory authorities don't seem to be worried about it but there's a reason why that this might cause problems a few years down the line because it's got the potential well we know it works by mutating viral rna and i want thorough reassurance that it doesn't mutate human rna and dna before i can comment further and we simply haven't got that data yet we're just at the stage of taking people's word for it and there's a theoretical reason why i'm uncomfortable with that the antidepressant one the selective serotonin uptake in here but i'm more than happy with that i've taken a course we've been using them for for years and years we've got millions and millions and probably a billion people around the world have taken them more than a billion um and and likewise with this new drug uh we've been giving them out since 1995 these protease inhibitors so i feel pretty comfortable that there's nothing that's going to come back to bite us in the ankle in years to come with this so so what we're not what i'm not worried about is the longer term side effects so what we need to look at is is the shorter term side effects and that's what this data gives us information on now they got safety data on 1881 people so slightly more than the number of people in the trial so more people had obviously taken the medication and actually reported the results emergent adverse events so the pax lovid group uh 19 of people complained of uh adverse events in the trial the placebo group 21 complained of adverse effects now people are always asking me how can if placebo is just a sugar pill or just a pill that contains nothing active how on earth can people get any effects from it at all well the answer is that if they can get beneficial effects called placebo effects or if they believe that they're of course these people don't know whether they're taking the active drug or or or not a placebo they know the one or the other they don't know which is which but if they're taking the placebo they know there's a 50 chance they're taking the real drug and they can actually develop side effects from that because they believe they could develop side effects and this is called the nocebo effect so it's like an inverse or negative placebo effect so the placebo effect makes people better because they believe they're going to get better the nocebo effect makes people feel worse and generates clinical symptoms because they believe that they might so that is what is happening uh there so we see that again very very nice comparison this is what clinical trials are all about we actually see no real significant difference between the groups um most most of which were mild in intensity so so most of most of people just carried on taking the medicine as a result of this um nothing particularly to raise alarms there not surprising because we're very familiar with protease inhibitors we've been using them for years there are recognized side effects on fat distribution and things like that but these are all well known and well recognized now fewer serious adverse events in the uh in the uh pax lovely group now um for serious adverse events in the pax loving group 1.7 of patients complained of serious adverse events in the placebo group 6.6 percent complained of serious adverse events so again looks like quite a few people had a no sibo effect but again we see that it's not showing it's any more dangerous than placebo in fact that's indicating that it's i would imagine statistically significantly safer than placebo which is a bit weird but you know in terms of getting the drug rolled out it's a good it's a good sign um so that's good now who what what about patients who had to discontinue um did discontinue use of the study drug due to adverse events well the pax lovely group um 2.1 percent of people who took it felt they had to discontinue because of side effects and adverse events in the placebo group 4.1 believe they had to stop taking it because of adverse events they couldn't carry on so again straight comparison and we see um it's looking pretty pretty impressively good surprisingly good data i know fizer themselves were taken aback by how amazing this data is of course we want peer review we want a lot more information but so far right just a few more things to round off pharmacology now they say this drug specifically designed so so that means it must be a variation size coronavirus 2 3cl so 3cl is the subclass of protease inhibitors so it's a bit it's a bit like you turn up to your building site with lots of long pieces of wood these are your big proteins and you need to cut these pieces of wood to put them into a window frame to make your building but uh someone's got hold of your saw and uh sabotaged your saw and made it all blunt so you can't saw the pieces of wood up therefore you can't fit them into the into the building that's the same thing these long proteins that are synthesized by the virus must be trimmed down into precise lengths to fit into the viral structure the proteases that trim the proteins the the proteases of the sores or the knives or the scissors that trim the proteins take those away the proteins are too long to fit into the virus therefore you can't you don't get viral replication it's a well-known well-known uh pharmacodynamic effect so this is an enzyme that uh coronavis need to replicate of course to cut the proteins into the right length now they're actually talking about co-administering a low dose of retinovir which is another which is another one of these similar drugs to help slow the metabolism of the neutrogena that's fine giving two drugs together it's very common to have uh we call this pharmacokinetic interactions so um that that's quite common it will prolong the half-life of the drug meaning you can give a lower dose which is fine um inhibits viral replication a stage known as proteolysis so proteins lysis means to break up in other words chopping the proteins up to the right length and that occurs before rna replication preclinical studies did not demonstrate evidence of mutagenic dna interactions which i agree with and it's not that i'm particularly happy with these uh with these uh pre-clinical studies what i am happy with is that i've personally been giving this drug out since uh well not all the time depends where i've been working but as i say i'm pretty sure i first gave this out in 1996. so this is a drug we are very uh or a group of drugs a group of drugs we're very familiar with um now include most of the patients who took this one vaccinated but include some vaccinated patients who've had an acute breakthrough of symptoms and who've had uh who also have risk factors for cov19 because we know that people that have been uh vaccinated who are older or have co-morbidities or it's been a while since they've been vaccinated we know that um they're still at risk of breakthrough infections which can result in hospitalization so it looks like it's good for those people as well it could be prescribed more broadly at home to help at a home treatment to help reduce illness severity which is good reduce hospitalizations reduce deaths as well as reduce the probability of infection following exposure amongst adults they're saying in other words what they're saying is this could be used as a prophylaxis now there's a trial that started in september that is looking at this specifically and we haven't got the results from that yet but if it's going to inhibit the pro if it's going to inhibit the formation of the virus then someone who's been going to be exposed isn't going to make the virus as normal and if you can't make the virus as normal you can't pass it on to other people and they're not going to get the illness so it's a prophylaxis as well which means you could you could actually take an area where there was an outbreak and kind of put a firewall around about it by giving this medication to stop the spread for example of a new variant this is how dramatic this this could potentially be um so um anyway anyway so the prophylactics studies the trial results should be out in that in a few months but they are being done demonstrate a potent antiviral in vitro activity against circulating variants of concern in other words in vitro at least not in vivo so in experiments in the lab it seems to work against all vocs which is good as well as other known coronaviruses so we haven't got um um sars coronavirus one now that's been eliminated from the world but we do have a lot of common colds we have four common colds caused by uh corona viruses so it might be potentially an anti-cold medication and of course we get a few hundred cases a year of the middle east respite syndrome which is very nasty from camels mostly in the middle east and it would be a treatment for that as well and would be interesting to see if this does have antiviral properties in groups of viruses outside coronaviruses don't know yet but it will be interesting to find that out i'm sure they're looking at that um potential as a therapeutic for multiple types of chronic virus infection yeah okay we'll just say a little bit about what the boss is saying chairman chief executive pfizer today's news is a real game changer now if all this checks out i agree with him on this occasion it is a real game-changer in the global effort to halt the devastation of this pandemic i agree um these data suggest that our oral antiviral candidate if approved or authorized by regulatory authorities has the potential to save patients life given on what we've read today yes reduce the severity of infections yes eliminate up to nine out of ten hospitalizations from this data yes um fulfilling our responsibility to help health healthcare institutions around the world he says while ensuring adequate and broad access to people everywhere now i'm hoping this is going to include people in uganda for example who can't afford basically hardly anything or they can't afford anything i'm hoping this is going to improve include people in the very poorest parts of the world to whom a dollar is a daily income now if if he maintain if he means this people everywhere means this has to be at a price which those people can afford which means it needs to be priced in the sense not in the dollars tens or hundreds of dollars we will see but i'm going to get a bit of tick because i'm going to give him the benefit of the doubt if he wants to come on and talk about that is more than welcome of course so there we go uh it is it is a potential amazing game-changer really quite staggering and as i say i feel much more comfortable about you know you know when you're talking about drugs you always want to go with familiar preparations and things that you you know about drugs that you have experienced with or if you can't have drugs that you're experienced with at least drugs that you're familiar with the group of drugs and again with the antidepressants with the with the flu voxamine and with these protease inhibitors we are already very familiar with them so um and we know how long is it since 1996 that's what 20 25 years ago or something so you know we've already got 25 years of safety data and it is pretty good so um there we go pretty pretty interesting uh and exciting and uh interesting to see which way the regulatory authorities jump um if they jump fairly quickly like the british authorities did with the uh mumbo pura via that would be more understandable than i'm not quite understanding why the british authorities jumped so equipped with normal periphery but with this one if regulatory authorities on both sides of the pawn jump fairly quickly i would find that much more comprehensible and feel much more comfortable with that sorry i've gone a bit longer but thank you for watching

Channel: Dr. John Campbell

Views: 426,070

Keywords: physiology, nursing, NCLEX, health, disease, biology, medicine, nurse education, medical education, pathophysiology, campbell, human biology, human body

Id: EMfjtgli55Y

Length: 26min 2sec (1562 seconds)

Published: Sun Nov 07 2021