With all the bad news about the pandemic across Europe, some good news is welcome.
While I recently lamented the lack of effective and accessible treatments for COVID19, it’s now all change with a flurry of anti-viral agents going though the process of trials and applications for authorisation which, with vaccines, could shift the balance of the pandemic.
Will this be the game changer for the pandemic? It is certainly very good news!
Despite waning effectiveness, vaccines remain good at prevention of severe illness, and in the UK, boosters will certainly make a big difference; but up till now we have few really practical direct anti-viral treatments for those at risk of serious illness who get infected.
Remdesivir was first off the block, having already been developed as a treatment of Ebola. However, results varied regarding its effectiveness, which was in any case severely limited by the need for inpatient intravenous infusion and its hideous cost of about £2000 per patient. Convalescent serum was also highly inconvenient with only marginal effectiveness. Repurposed drugs showed some promise, though all with limited effectiveness, such as Fluvoxamine, which reduced the risk of admission by an impressive but not earth shattering 30%.
Astra Zeneca also developed a treatment called AZD7442, consisting of two long acting antibodies derived from the B (white blood) cells of COVID survivors. When taken within three days of symptom onset it cut the risk of severe illness or death by 88%. It is given by injection, again a disadvantage, as well as the cost rumoured again to be about an impractical £2000 per patient. Despite this price tag, the US have bought 700,000 doses, but with cheaper oral treatments in the pipeline, they will send them back?
Molnipiravir was the first giant leap forward, reducing the need for hospitalisation by a more than worthwhile 50%.
The five day course of pills works by inserting the wrong sequences of building blocks into viral RNA, thus making replication impossible. Rather like changing random letters in a sentence which then doens’t make sense.
There are, however, some concerns about its ability to create mutations which may lead to new variants, particularly as treatment would be targeted at people with less effective immune systems. Concerns too about potential change in the DNA of sperm cells. Indeed in their trials those potentially pregnant were excluded and advice given to avoid sex for a month after treatment.
This may not be a problem in the real world when most patients who need treatment will be well past reproductive age. Other experts are not so worried, but there are issues of concern.
Almost immediately, it was overtaken by the latest innovation off the production line.
Paxlovid is significantly better at reducing serious illness with reduction in the need for hospital of 89% if treated in the first three days of symptoms and 85% within five. The trial included 1200 patients with COVID, with the 10 deaths all in the placebo group. It reduced the risk of admission from 6.7% to 1%.
Paxlovid contains two anti virals, one called PF-07321332 which is a specific Sars-Cov2 viral protease inhibitor, knocking out the enzyme responsible for duplication of viral proteins and thus prevents infections from progressing. The other, ritonavir, inhibits its breakdown so the active drug hangs around longer.
Factories are tooling up in Ireland and Germany to increase output.
Paxlovid is a tablet taken twice daily for five days.
Although the full results are still to be published, the trial outcomes seem very exciting and the company has applied for Emergency use with the FDA. Having said that, it is very unlikely to be on the shelves this year, though not long after. Governments of the wealthier nations are queuing up to stockpile the drugs, with the US buying up 10 million courses, with the UK and EU nations in hot pursuit.
Problems and solutions
Both Paxlovid and Molnipiravir look like costing about $700 a course, though this has yet to be officially announced. While pricey, it is a drop in the ocean when compared to the hospital costs saved by reductions in admissions. Nonetheless we in UK were first to give it official approval to Molnipiravir and started stockpiling it We have purchased 450,000 doses and have ordered 250,000 doses of Paxlovid. I am optimistic that the Tamiflu fiasco, (where governments spent billions stockpiling an influenza drug which basically did not work), will not be repeated as the trial data is so encouraging.
These new antivirals look like tipping the balance against Sars-Cov-2.
The drug companies have designed tiered pricing mechanisms so the drug can be made available to poorer countries and agreed to relax its license to allow for production of cheap generics – at least partially. It needs to be made available globally to enable health systems to cope and this at least represents some progress.
As with all antibiotics, there is the problem of the development of resistant variants. If this is the case with these antivirals, it can be worked around by offering combination medications rather like the incredible success in treatment for HIV. We may well see developments in this area soon as new antivirals emerge.
Meanwhile, across the pond, some of the most energetic proponents of Ivermectin as an effective COVID19 treatment are having an interesting time….
Ivermectin’s latest ding dongl!
Earlier this year the FLCCC, a group of American doctors led by Pierre Kory who are keen on early and aggressive treatment called the MATH+ protocol published results which showed huge benefits from their cocktail of medications and vitamins. The halving of mortality they found was sung from the rooftops and became a big driver of the Ivermectin craze fuelled by emotive appearances in the media and in Congress hearings. Some aspects of the protocol made sense – steroids have become standard treatment after clear benefits emerged from quality trials, but many others have fallen foul of evidence, and now there are big questions about their results.
Sentara hospital, whose patients were used in the study, raised concerns that the data published by Kory and others were not accurate.
The journal then looked more closely at the study and found errors so huge it is hard to avoid the accusation of fakery. When they checked the hospital data, they found the mortality of patients treated was not reduced to half that of the untreated, as claimed, but in fact those patients who received all four MATH+ therapies had a mortality of 28% compared to 10% in those treated conventionally.
In other words, those treated with the full protocol died at nearly three times the rate of than those not subjected to the the protocol. Sentena have prohibited doctors they employ from prescribing much of the protocol, including Ivermectin.
The high profile publishing doctors, it seems to me, must be in hot water over what seems to be such clear evidence of falsification of data. Disciplinary measures against some nutty US medics has so far, been administered with a gentle velvet glove. However, this is the USA, so off we go to the courts….
What seems certain from this saga is that the doctors should agree to immediately STOP using the protocol. Yet Paul Marik, one of the leading proponents of the MATH+ protocol is now suing Sentena hospital for preventing him from doing so – despite the results suggesting the reason they have done this it to prevent demonstrable harm. As usual he modestly announces himself as the “World’s Leading ICU Doctor….” In the litigious American culture it seems the courts rather than science, will decide who is right. This is fraught with danger.
Marik’s lawsuit, filed in Norfolk Circuit Court, does indeed not ask the court to reach a scientific judgment. (I wonder why) Rather, it claims that Sentara’s ban “violates patients’ right to informed consent”. In other words, patients have the right, they argue, to be prescribed drugs that don’t work if they so choose
Whatever the outcome, I doubt the Ivermectin fanatics will reflect. There have even been insane claims that Pfizers new drug is simply rebranded Ivermectin: Pfizermectin they say! It will be hard for some to let this Ivermectin idea go and Im sure another conspiracy theory will emerge from all this, irrespective of the judges verdict, expected in late November.
There are people in the UK now buying and selling Ivermectin as a potential cure for COVID19. I get a bit narked by this. Not only is this illegal, but also assumes the seller has the background needed to prescribe the drug sensibly. Dishing it out to anyone who wants it is one thing – safe prescribing another.
Knowledge and understanding of the particular patient, dosages, interactions with other drugs, potential side effects and harms as well as follow up are all part of the jigsaw which needs to be assembled for safe prescribing. It is dangerous if prompt, effective treatment is delayed by a belief that Ivermectin will keep anyone out of hospital. It won’t.
Back on Earth
The new antivirals drugs are not a magic bullet, but will be a giant leap forward.
They will not resolve the need for time off work or school for those infected, nor will they have much of an impact on long Covid, with which so many people struggle. Yet the availability of effective anti-virals will potentially make a big difference to hospital admissions and deaths. This will take the pressure off the acute health sector struggling all over the world.
With effective antivirals, restrictions being introduced across the world in the face of increasing infections could be relaxed, vaccine mandates replaced by more gentle persuasion and health resources concentrated on dealing with the backlog of patients and day to day consequences of our unhealthy societies
They will cost money too, not as much as a ITU full of COVID patients, but will add to the need for the government to increase their borrowing and income. Of course, this will be in addition to the investment needed to transform transport, energy, consumption, urban planning and waste we desperately need and soon.
The bigger, more expensive threats loom large – climate change is evident in day to day life now. I have poppies germinating and flowering in my polytunnel in November without there being any chance of pollination. Cowslips in November too. Not worth a call to 999, but small signs of problems ahead which will dwarf the impact of COVID, both in human and financial cost.
For now, stay as well as you can. I have just had my booster and so approach the winter knowing my changes of infection have been reduced by 95%. However it is clear the increased infectiveness of the virus means it will spread to everyone, and immunity from vaccination or previous infection will be really useful. More on the details of that in my next post.
Staying well too, and using the effective public health measures which the government seem so reluctant to embrace.
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