Treatments

U.K. Drug Regulator Approves First Drug to Treat Coronavirus

The first drug which effectively treats coronavirus has been approved by the U.K.’s medicines regulator and is being introduced “as soon as possible” on the NHS. No, it’s not ivermectin. It’s Ronapreve, the same drug, or combination of drugs, used to treat Donald Trump last year. The Times has more.

Ronapreve uses man-made antibodies and prevents the worst symptoms of the virus. The drug is either injected or given through a drip and acts at the lining of the respiratory system where it binds tightly to the virus and prevents it from gaining access to cells.

In June, a large U.K. trial involving nearly 10,000 people found the drug cut the risk of death by about 20% in hospital patients whose bodies were not making antibodies to fight coronavirus.

Donald Trump hailed the treatment as a “cure” and a “blessing from God” after he received an experimental drug cocktail in October last year. It was given emergency authorisation in the US the following month and is thought to cost between £1,000 and £2,000 per person.

Martin Landray, Professor of Medicine and Epidemiology, at Nuffield Department of Population Health, University of Oxford, said: “It combines two antibodies that bind to different places on the coronavirus spike protein, preventing uptake by cells and accelerating clearance of the virus. The rationale for combining two different antibodies is that if a viral variant prevented one drug from binding to the spike protein, the other would still be effective – a ‘belt and braces’ approach.

“This licensing decision is an important step forward. There have been a number of trials in the out-of-hospital setting, each with positive results – reducing viral clearance and reducing the risk of hospitalisation. There have been no major safety concerns.

“The challenge going forward will be in determining which patients should be prioritised for this treatment.”

The Medicines and Healthcare Regulatory Agency (MHRA) said Ronapreve may be used to prevent infection, promote resolution of symptoms of acute COVID-19 infection and reduce the chances of being admitted to hospital.

Worth reading in full.

“Open a Window”: How Many Are Dying Because This is Still the Best ‘Treatment’ the NHS Offers to Those Suffering With COVID-19 at Home?

The highly recommended HART bulletin this week has a piece on how the NHS is failing Covid patients by not offering any adequate early treatment, despite the now plentiful evidence of the clinical effectiveness of a number of safe, repurposed drugs.

Nearly a year and a half after the country was locked down to protect the NHS, how is the NHS performing in managing the very condition that so threatened it?

If you suspect that you or a member of your household is suffering from COVID-19 the advice is to get a test and contact NHS 111 for advice. When you do this you are asked a series of questions designed to ascertain how seriously ill you are. If you report “red flag” symptoms such as severe breathlessness or oxygen saturations below 90% quite rightly you are advised to call 999. But what about the less severe cases? The National Institute for Health and Care Excellence (NICE) has issued guidance to clinicians on how to assess and manage patients with COVID-19. Patients not severely ill and requiring hospital admission are managed in the community. The guidance advises symptomatic treatment such as a teaspoon of honey or linctus or even morphine sulphate tablets to suppress coughing. This in itself is bizarre advice, given that the British National Formulary (BNF) only recommends morphine for treatment of cough in palliative care with a ‘reminder of the risk of potentially fatal respiratory depression’.  Paracetamol or ibuprofen is recommended for fever. For breathlessness it advises to keep the room cool and open a window. For agitation and anxiety it even recommends a trial of a benzodiazepine (a tranquiliser medication) despite this potentially leading to respiratory depression.

What does not feature in the guidance is early treatment of COVID-19 in the community. Drug treatments such as dexamethasone and remdesivir are recommended for hospital patients. There are a number of established medicines such as ivermectin, hydroxychloroquine, zinc and famotidine which have been advocated for early treatment. The evidence in favour of ivermectin, in particular, is growing rapidly as this meta-analysis by HART member Professor Norman Fenton and his colleague Professor Martin Neil shows.

Similarly, early administration of inhaled budesonide (an asthma drug) has been shown to reduce the likelihood of needing urgent medical care and reduced time to recovery while a peer-reviewed study in the USA showed fluvoxamine (a common antidepressant drug) prevented clinical deterioration in outpatients with clinical COVID-19.

The U.K. has been quick to roll out COVID-19 vaccines that are still undergoing their clinical trials yet seems reluctant to explore the possibility of cheap treatments with long established safety records. Surely this begs the question why?

Read the bulletin in full here and sign up to receive the next one here.

“100% Effective in Preventing Hospitalisation and Death”: Repurposed Drug Fluvoxamine Shows Promise for Treating COVID-19

Steve Kirsch at TrialSiteNews has written an excellent new overview of the evidence on three COVID-19 treatments that have been unfairly overlooked or maligned by health authorities including the World Health Organisation and the U.S. National Institutes of Health. They are hydroxychloroquine, ivermectin, and fluvoxamine, and despite consistently good evidence of their effectiveness in early treatment, Western and global health authorities have remained either neutral about them or recommended against their use. Kirsch goes in some detail through the evidence on each and suggests governments should set aside the guidance of the WHO and NIH and “independently evaluate the evidence”.

The whole piece is worth reading in full, but I particularly want to highlight here the section on fluvoxamine, which is a promising drug that has not received the prominence the emerging data on it should warrant even among many with their ear to the ground on repurposed treatments.

Fluvoxamine, which is commonly used as an anti-depressant though has more general anti-inflammatory effects, is not acknowledged by the WHO at all in connection with COVID-19. However, Kirsch notes that the NIH is more up-to-date on this one.

The NIH is better; it is listed on the NIH’s Covid Treatment Guidelines, and the NIH  knows that there have been two quality randomised trials done by top US researchers (one trial was a DB-RCT, the other was quasi-randomised which the NIH categorises as “observational” but that’s a debate for another op-ed), both were published in peer-reviewed journals, and both papers were given a prestigious “Editor’s Choice” designation.

In other words, fluvoxamine has something that ivermectin and HCQ both lack: two quality studies, done by highly respected researchers associated with top-quality institutions, published in top peer-reviewed journals, both studies had statistically significant results on a critical clinical endpoint (hospitalisation), both were an interventional trial, both were randomised, and both studies were highlighted by the editors. It is for these reasons that the mainstream scientific community believes that the case for fluvoxamine is superior to the case for ivermectin and HCQ. 

Of the most respected scientists I know, 100% would choose fluvoxamine in a heartbeat over the other two drugs if they got Covid and had to pick a treatment based on the evidence available today. A top medical school looked at fluvoxamine and other options and the consensus was that the case for fluvoxamine was clearly the strongest. I also know of a DB-RCT study, not yet published, which compared the efficacy of fluvoxamine against ivermectin and fluvoxamine had the greater benefit by far.

The consistent superior rating by mainstream scientific experts is important because if a country adds ivermectin and/or HCQ to their treatment recommendations, then adding fluvoxamine should be a “no brainer.” Unfortunately, this isn’t the case today, anywhere in the world. However, the FLCCC did add fluvoxamine to their early outpatient treatment guidelines based on the evidence and the experience with doctors all over the world with the combination.

Fluvoxamine’s safety record is also known and good, Kirsch says.

Ivermectin: Cheap Covid Treatment Shown to be Highly Effective in New Peer-Reviewed Study

A new peer-reviewed study by Dr Pierre Kory and colleagues on Ivermectin has been published in the American Journal of Therapeutics. Entitled “Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19“, it provides a new authoritative overview of the evidence to date and calls for the widely available drug to be “globally and systematically deployed in the prevention and treatment of COVID-19”.

The study summarises the impressive evidence base for the use of Ivermectin.

1. Since 2012, multiple in vitro studies have demonstrated that Ivermectin inhibits the replication of many viruses, including influenza, Zika, Dengue, and others.
2. Ivermectin inhibits SARS-CoV-2 replication and binding to host tissue through several observed and proposed mechanisms.
3. Ivermectin has potent anti-inflammatory properties with in vitro data demonstrating profound inhibition of both cytokine production and transcription of nuclear factor-κB (NF-κB), the most potent mediator of inflammation.
4. Ivermectin significantly diminishes viral load and protects against organ damage in multiple animal models when infected with SARS-CoV-2 or similar coronaviruses.
5. Ivermectin prevents transmission and development of COVID-19 disease in those exposed to infected patients.
6. Ivermectin hastens recovery and prevents deterioration in patients with mild to moderate disease treated early after symptoms.
7. Ivermectin hastens recovery and avoidance of ICU admission and death in hospitalised patients.
8. Ivermectin reduces mortality in critically ill patients with COVID-19.
9. Ivermectin leads to temporally associated reductions in case fatality rates in regions after ivermectin distribution campaigns.
10. The safety, availability, and cost of ivermectin are nearly unparalleled given its low incidence of important drug interactions along with only mild and rare side effects observed in almost 40 years of use and billions of doses administered.
11. The World Health Organisation has long included ivermectin on its “List of Essential Medicines.”

The quality of the evidence for Ivermectin has been challenged, leading many countries including the U.K. and U.S. not to recommend its use for COVID-19. The study takes this criticism head-on.

Although a subset of trials are of an observational design, it must be recognised that in the case of ivermectin (1) half of the trials used a randomised controlled trial design (12 of the 24 reviewed above) and (2) observational and randomised trial designs reach equivalent conclusions on average as reported in a large Cochrane review of the topic from 2014. In particular, OCTs that use propensity-matching techniques (as in the Rajter study from Florida) find near identical conclusions to later-conducted RCTs in many different disease states, including coronary syndromes, critical illness, and surgery. Similarly, as evidenced in the prophylaxis and treatment trial meta-analyses as well as the summary trials table, the entirety of the benefits found in both OCT and RCT trial designs aligns in both direction and magnitude of benefit. Such a consistency of benefit among numerous trials of varying sizes designs from multiple different countries and centres around the world is unique and provides strong, additional support.

A hint of the politics around Ivermectin can be gleaned in the discussion section, where the authors wonder how much more evidence a cheap, safe drug like Ivermectin needs in an international emergency before it can be approved.

The continued challenges faced by health care providers in deciding on appropriate therapeutic interventions in patients with COVID-19 would be greatly eased if more updated and commensurate evidence-based guidance came from the leading governmental health care agencies. Currently, in the United States, the treatment guidelines for COVID-19 are issued by the National Institutes of Health. Their most recent recommendation on the use of ivermectin in patients with COVID-19 was last updated on February 11th, 2021, where they found that “there was insufficient evidence to recommend for or against ivermectin in COVID-19”. For a more definitive recommendation to be issued by major leading public health agencies (PHA), it is apparent that even more data on both the quality and quantity of trials are needed, even during a global health care emergency, and in consideration of a safe, oral, low-cost, widely available and deployable intervention such as ivermectin.

Boris Warns of Third Wave – as He Finally Gets Round to Looking at Treatments for Covid

Boris told the country yesterday that, despite the vaccines, there is going be “another wave of Covid” at some point this year. Speaking at a Downing Street press briefing, he said:

As we look at what is happening in other countries with cases now at record numbers around the world, we cannot delude ourselves that Covid has gone away. I see nothing in the data now that makes me think we are going to have to deviate in any way from the roadmap, cautious but irreversible, that we have set out. But the majority of scientific opinion in this country is still firmly of the view that there will be another wave of Covid at some stage this year and so we must – as far as possible – learn to live with this disease, as we live with other diseases.

The warning came as he announced a task force to find new ways of treating COVID-19 before winter, with the aim of developing a tablet that can be taken at home to provide crucial early treatment. He said:

This means for example that if you test positive for the virus that there might be a tablet you could take at home to stop the virus in its tracks and significantly reduce the chance of infection turning into more serious disease.

The task force is welcome, of course, but the question is why is it only just being set up, when we first knew of this virus in January of 2020? Why wasn’t finding effective treatments a priority from the start? Why did none of the journalists at the press conference ask this question? Treatment should always be the first solution reached for when faced with a disease, as unlike lockdowns and vaccines they provide a way of making sick people better.

While the idea of learning to live with the disease, including through the use of treatments, should be reassuring, what the politicians mean by the phrase in the past year has typically turned out to be quite different to what most of us mean by it. We mean getting back to normal. They mean setting up a new “normal” of vaccine coercion, biometric ID passes, permanent screening programmes, face masks, closed borders, and restrictions on social contact and basic freedoms that loosen and tighten depending on the questionable results of mass testing. No thanks.

So why now? Is the Government only turning to treatments at this point because its fears are growing about variants that can escape the vaccines (for which there is some evidence)? Is this a further sign that the Government and its scientists are losing confidence in the vaccines?

In fact, as Professor Philip Thomas argues, there is unlikely to be a “third wave” now that we have the vaccines to top up our acquired and pre-existing immunity (and I doubt there would be a “third wave” without the vaccines). The remarkably low Covid hospitalisation rate for people who’ve been vaccinated that was reported yesterday adds to that hope. However, there is always going to be a winter flu season, and Covid and its potentially immunity-stretching variants are always going to be around. Who knows what the future will bring? Certainly not SAGE and its discredited modelling teams, whose alarmist predictions have consistently fallen flat. (Even in winter they predicted a much bigger surge and failed to anticipate that it would peak before lockdown.)

The question that has never been answered in this crisis is how safe do we need to be from Covid before we can go back to normal? Actually, it was answered once. In the Government’s original Pandemic Preparedness Strategy we know that a death toll of up to 315,000 within a few months from a pandemic virus was envisaged as being acceptable – still far more than we have seen with the (PCR-inflated) Covid death toll of the past year. That scale of mortality was not deemed to warrant any of the unprecedented measures we have experienced since March 2020 (which in any case were, correctly, judged not to be effective).

But since that sensible, science-based plan was ditched, the key question of when we can return to normal – the old normal, not the new normal – has never been answered. Is it because to do so would mean the politicians and scientists would have to grow a spine and endorse an acceptable level of risk and bring the emergency – and their status in it – to an end?

What’s the Truth About Budesonide?

Since Lockdown Sceptics reported on Sunday about the remarkable effectiveness of the common asthma treatment Budesonide against COVID-19 – cutting serious disease by 90% according to a study published in the Lancet – a new study has appeared underlining its effectiveness as a Covid treatment.

The first study was part of the STOIC trial at Oxford University and found that 10 of the 73 symptomatic Covid patients in the control group required urgent medical care (e.g. hospitalisation) compared to just one of the 73 symptomatic Covid patients who inhaled Budesonide twice a day. This translates to 87% effectiveness in preventing serious disease. One limitation of the study was that few of the participants were high risk or elderly, with an average age of 45; another was that it was small.

The new study is from the PRINCIPLE trial, also based at Oxford, and uses a larger group (751 using Budesonide, 1,028 in the control group), all of whom are either over 65 or over 50 with a risk-increasing underlying health condition. It found that Budesonide reduced a patient’s time to recovery by an average of three days (11 days compared to 14), and also reduced the chances of a relapse within 28 days.

Disappointingly, however, those who took Budesonide were only slightly less likely to be admitted to hospital – 8.5% compared with 10.3% – and this result was not statistically significant (though the trial is to be expanded which may address this issue).

Professor Richard Hobbs of Oxford University, who co-leads the trial, said: “For the first time we have high-quality evidence of an effective treatment that can be rolled out across the community for people who are at most risk of developing more severe illness from COVID-19. Unlike other proven treatments, Budesonide is effective as a treatment at home and during the early stages of the illness. This is a significant milestone for this pandemic and a major achievement for community-based research.”

On Monday, an alert was sent to the NHS saying the drug can now be used off-label for the treatment of COVID-19 for the over-65s and at-risk over-50s, the Telegraph reports.

This is good news. However, not everyone is convinced. The ‘Swiss Doctor’ notes that the trials have financial ties to Budesonide manufacturer AstraZeneca, and that the results are not as impressive as the newspaper reports might suggest. For example, they use “soft” rather than “hard” endpoints.

In both trials, Budesonide achieved no significant improvement in any “hard endpoint”: in the PRINCIPLE trial, there was no significant difference in hospitalisations, deaths, hospital assessment without admission, oxygen administration, and ICU admission. In the Oxford [STOIC] trial, there was no significant difference in the proportion of people and days with an oxygen saturation below 94%, PCR cycle threshold increase, and FluPRO-measured symptom resolution.

The “soft” endpoints were “self-reported recovery” in PRINCIPLE and “urgent care visits” in STOIC, of which only one patient was actually hospitalised and required oxygen.

The ‘Swiss Doctor’ does concede that there was some indication of benefit to the high-risk in the PRINCIPLE trial: hospitalisation/death risk was lower (8.5% vs 10.3%), oxygen requirement was lower (5.8% vs 8.4%), and ICU admission was lower (1.2% vs 2.2%). However, the trial will need to expand if these differences are to gain statistical significance.

The positive results for Budesonide are certainly welcome, as is the news that the NHS has been given the green light to prescribe it for high-risk groups. Though why not for the low risk under-65s as well? In the STOIC trial it cut the need for urgent care to close to zero in that group. Is that not a worthwhile medical intervention, particularly with all the worry about ‘long Covid’?

It’s fair to say that the 17% reduction in hospitalisation/death among the high risk is disappointing when compared to the impressive 87% reduction in urgent care among the low risk. But it’s still an improvement, and the other indicators – shorter recovery time, reduced need for oxygen and intensive care – are also encouraging.

I should add that what we’re really waiting for are high quality results on the highly promising Ivermectin that are deemed acceptable to the health regulators so that drug can become generally available. No rush, guys. Not like people are dying or anything.

Cheap, Safe Treatment Cuts Serious COVID-19 by 90%, Oxford Study Shows

A study from Oxford University has confirmed the remarkable effectiveness of common asthma treatment Budesonide for treating COVID-19.

First published as a pre-print in February and now as a peer-reviewed paper in the Lancet, the STOIC phase 2 randomised study found that inhaled Budesonide given to patients with COVID-19 within seven days of symptom onset reduced the relative risk of requiring urgent care or hospitalisation by 90%. It also resulted in a quicker recovery time for those who experienced fever and other symptoms and fewer persistent symptoms after 28 days, suggesting it could help to reduce the incidence of ‘long Covid’ in those given it as an early treatment.

Budesonide is a corticosteroid used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD). The study, which is supported by the Oxford Biomedical Research Centre (BRC) and AstraZeneca, involved 146 people, half of whom took 800 micrograms of the medication twice a day while half were on usual care. It was confirmed to be safe (unsurprising for an established medicine), with only five (7%) participants reporting self-limiting adverse events.

Professor Mona Bafadhel of Oxford’s Nuffield Department of Medicine, who led the trial, said: “I am heartened that a relatively safe, widely available and well studied medicine such as an inhaled steroid could have an impact on the pressures we are experiencing during the pandemic.”

The trial came into being because clinicians noted early on in the pandemic that patients with chronic respiratory disease, who are often prescribed inhaled steroids, were significantly under-represented among those admitted to hospital with COVID-19, despite the condition being a likely risk factor.

Budesonide is unusual because, unlike Vitamin D, Hydroxychloroquine and Ivermectin, it has not (yet) been (unfairly) rubbished in the mainstream press and medical literature. For those other potential treatments you can see the studies for yourself here and read a fair overview here.

If a highly effective early outpatient treatment for COVID-19 becomes available then that may change everything in terms of vaccine programmes and exit strategies. The COVID-19 vaccines are currently authorised not under ordinary marketing licences but under temporary emergency approval. This approval is conditional on there being a current medical emergency. In the EU emergency approval can only be for an “unmet medical need”, and the approval is reviewed annually. In the US there must be no “adequate, approved, and available alternatives”. In the UK a disease must be a “serious risk or potentially serious risk to human health”, though there is no requirement to review the temporary approval.

An efficacy in reducing serious disease by 90% would rival the reported efficacy of the vaccines. The trial did not include many in high risk groups such as the elderly or those with underlying conditions, but vaccine effectiveness is also reduced in these groups.

As proven effective treatments like Budesonide come online, will the Government’s case for draconian interventions and coerced vaccinations, even on its own twisted terms, fall away?