Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial

‘This is, to the best of our knowledge, the first large, randomised controlled trial to test the efficacy of fluvoxamine for acute treatment of COVID-19. We found a clinically important absolute risk reduction of 5·0%, and 32% RR reduction, on the primary outcome of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19, consequent on the administration of fluvoxamine for 10 days. This study is only the second study to show an important treatment benefit for a repurposed drug in the early treatment population.13 Our findings represent the complete analysis of the trial after the DSMC recommended stopping the active fluvoxamine group and all 28-day follow-up of randomly assigned patients. Given fluvoxamine's safety, tolerability, ease of use, low cost, and widespread availability, these findings might influence national and international guidelines on the clinical management of COVID-19.’

Read here (The Lancet, Oct 27, 2021)

DCGI approves anti-Covid drug developed by DRDO for emergency use

‘The Drugs Controller General of India (DCGI) has granted permission for emergency use of anti-COVID-19 therapeutic application of the drug 2-deoxy-D-glucose (2-DG) developed by Institute of Nuclear Medicine and Allied Sciences (INMAS), a lab of Defence Research and Development Organisation (DRDO), in collaboration with Dr. Reddy’s Laboratories (DRL),Hyderabad. 

‘In a release issued on Saturday, the Ministry of Defence said that as per the order, emergency use of this drug as adjunct therapy in moderate to severe COVID-19 patients is permitted. It added that being a generic molecule and analogue of glucose, it can be easily produced and made available in plenty in the country. 

‘The drug comes in powder form in sachet, which is taken orally by dissolving it in water. It accumulates in the virus infected cells and prevents virus growth by stopping viral synthesis and energy production. Its selective accumulation in virally infected cells makes this drug unique.

‘Clinical trial results have shown that this molecule helps in faster recovery of hospitalised patients and reduces supplemental oxygen dependence, noted the release.’

Read here (The Hindu, May 8, 2021)

Revealed: How a single pill home cure for Covid could be available this year

‘At two anonymous Pfizer buildings, one in the US and one in Belgium, a remarkable experiment is under way. Up to 60 volunteers, all clean-living adults aged between 18 and 60, are being given the first pill specifically designed to stop SARS-CoV-2.

‘If the trial is successful, it is just possible that a home cure for Covid-19 will become available later this year. The Prime Minister, who announced the formation of a UK Antivirals Taskforce last week specifically to invest in such products, will no doubt be scanning his text messages for early updates.

‘The molecule being tested is a bespoke antiviral codenamed PF 07321332. Classed as a "protease inhibitor", it has been formulated to attack the "spine" of the SARS-Cov-2 virus and stop it replicating in our noses, throats and lungs. It was protease inhibitors that turned the tide on the spread of HIV in the UK and around the world. Now researchers hope they may be on the brink of a similar pandemic-busting breakthrough.’

Read here (The Telegraph, Apr 24, 2021)

Large clinical trial to study repurposed drugs to treat Covid-19 symptoms

‘The National Institutes of Health will fund a large, randomized, placebo‑controlled Phase 3 clinical trial to test several existing prescription and over-the-counter medications for people to self-administer to treat symptoms of COVID-19. Part of the Accelerating COVID‑19 Therapeutic Interventions and Vaccines (ACTIV) public–private partnership, the ACTIV-6 trial aims to provide evidence-based treatment options for the majority of adult patients with COVID-19 who have mild-to-moderate symptoms and are not sick enough to be hospitalized. NIH will provide an initial investment of $155 million in funding for the trial.

‘Several drugs currently are recommended for the treatment of hospitalized patients with moderate to severe COVID-19, including the antiviral drug remdesivir, the anti-inflammatory baricitinib, and corticosteroids. Additionally, the U.S. Food and Drug Administration authorized emergency use of intravenous monoclonal antibodies in non-hospitalized patients with mild to moderate COVID-19 who are at high risk for severe disease. However, medications that can be self-administered at home to reduce COVID-19 symptoms are critically needed.’

Read here (NIH, Apr 19, 2021)

Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

‘The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.’

Read here (Nature, Apr 16, 2021)

The race for antiviral drugs to beat Covid — and the next pandemic

‘Despite dire warnings, a stockpile of ready compounds to fight viral pandemics was sorely lacking. Can drugmakers finally do the right thing?...

“What we will hopefully find”, he [Alejandro Chavez, a bioengineer and antiviral drug researcher at Columbia University Irving Medical Center in New York City] says, “are inhibitors that work on, if you’re really lucky, an entire family.” That would make the best-case scenario a pan-coronavirus inhibitor. But a more reasonable goal might be developing a drug for a subset of coronaviruses, such as alphacoronaviruses, which currently cause non-lethal infections in humans, and having a different drug for betacoronaviruses, the group responsible for SARS, MERS, and COVID-19.

‘Once the viral lineage is identified, “the same principles of drug discovery apply”, says Marnix Van Loock, head of emerging pathogens at Johnson & Johnson’s global public-health unit in Beerse, Belgium. As he explains, researchers need to find ‘druggable pockets’ on the surface of essential enzymes that are conserved between related viruses and can be used to design active molecules.’

Read here (Nature, Apr 14, 2021)

With great caution, scientists seek Covid treatments in old drugs

‘After two small studies, a cheap drug shows promise. But scientists still feel burned by hydroxychloroquine.

‘Repurposing is a long shot, yet compared to creating drugs and vaccines, the approach has clear advantages during a fast-moving pandemic. “If it works and it’s on the shelf, you don’t have any development time,” said Lisa Danzig, a specialist in infectious diseases who consults with companies, investors, government and philanthropies. One of the best treatments in the Covid arsenal — the common steroid dexamethasone — is a repurposed drug. But it is recommended only for hospitalized patients who are seriously ill.

‘Danzig was “very excited” last April by news that a team led by University of California-San Francisco researchers had identified 69 possible drugs that, when used early on, might counteract infections with SARS-CoV-2, the virus that causes Covid. “I’m thinking, if we can rapidly test some of these in clinical trials, we can have answers by October.”

‘Yet these studies struggled to get off the ground...’

Read here (Undark, Mar 30, 2021)

Molnupiravir: A new hope for prevention and treatment of Covid-19 and other dangerous viruses

‘The positive results of Molnupiravir represent an emerging hope for more Covid-19 therapies to come. Its oral administration indicates a potential drug that could come before hospitalization and perhaps even prevent severe symptoms. Were a pill-based treatment for Covid-19 available, many lives would be easily saved and many hospital beds could be opened for those who need them. 

‘In addition to its reduction of Covid-19 transmission, Molnupiravir is likely to be useful against influenza, ebola, and a large swath of other viruses as well. Its development appears to be a major advancement in virus control and should be active against Covid-19 variants and variants of other viruses. However, we caution Molnupiravir should be administered in conjunction with other therapies to avoid viruses rapidly developing resistance, which all these viruses are well-equipped to do. 

‘Though, as these results are preliminary, we eagerly await the full release of the phase two data and the drug’s eventual full trial outcomes. This could be a real winner.’

Read here (Forbes, Mar 16, 2021)

UK clinical trial confirms SaNOtize’s breakthrough treatment for Covid-19

• Patients with a self-administered nasal spray application found to have reduced SARS-CoV-2 log viral load by more than 95% in infected participants within 24 hours of treatment, and by more than 99% in 72 hours
• Trial concluded that treatment accelerated clearance of SARS-CoV-2 by a factor of 16-fold versus a placebo
• Randomized, double-blind, placebo-controlled trial evaluated 79 confirmed cases of COVID-19, the majority heavily-infected with the UK variant
• No adverse events were recorded in the group
• Submission for Emergency Use in the UK and Canada for the treatment and prevention of COVID-19 is planned immediately

Read here (Business Wire, Mar 15, 2021)

Covid: Asthma drug 'speeds up recovery at home'

‘A cheap drug, commonly used to treat asthma, can help people at home recover more quickly from Covid-19, a UK trial has found.

‘Two puffs of budesonide twice a day could benefit many over-50s with early symptoms around the world, said the University of Oxford research team.’

Read here (BBC, Mar 12, 2021)

Oral Covid-19 treatment yields promising trial data: Drugmakers

‘German pharmaceutical giant Merck and a US partner reported promising results on Saturday (Mar 6) in trials of a drug administered orally to fight COVID-19, saying it helps reduce patients' viral load...

‘In January, Merck halted work on two COVID-19 vaccine candidates but has pressed on with research into two products to treat the disease, including a pill-based one called molnupiravir, which it has developed with Ridgeback Biotherapeutics.

‘This drug caused a significant drop in patients' viral load after five days of treatment with it, Merck said at a meeting with infectious disease experts. This Phase 2A test - drug trials have three stages before a product can be approved - was carried out among 202 non-hospitalised people with symptoms of COVID-19.’

Read here (Channel News Asia, Mar 7, 2021)

The raging evolutionary war between humans and Covid-19

‘Fighting the pandemic isn’t only about vaccines and drugs. It’s about understanding how viruses mutate and change inside us, and among us...

‘The major change to the immunity of all the hosts SARS-CoV-2 is likely to try to infect will be, of course, vaccination. That’s human ingenuity fighting viral expertise, but it can also exert a kind of direct adaptive pressure on the virus. History has examples of so-called leaky vaccines—those that aren’t effective enough to prevent all infections or all transmission, and allow better-adapted variants of whatever bug they’re trying to squish to live to fight another day.

‘In fact, one group of researchers has a model that suggests that could even happen with the new batch of vaccines against Covid—especially those that require two doses and seem to confer different levels of immunity depending on how far apart they’re administered, or whether someone skips the second one. Here's how: If one extreme is a population totally naive to a new virus, completely vulnerable and with no immunity, and the other extreme is a population with perfect sterilizing immunity, what happens to a population in between? If a vaccine allows infection but no transmission, the virus doesn’t have a chance to evolve.

‘But if a vaccine or vaccination strategy allows some infection and some transmission? “The ones that are the best at getting around the host’s defenses are the ones that are most likely to persist,” says Caroline Wagner, a bioengineer at McGill and one of the people working on the model. If that’s all true, a leaky vaccine or leaky vaccination strategy could actually drive antigenic drift and create even worse variants. Wagner and her colleagues acknowledge that they don’t have enough data to put bounds on their model yet, but they worry about strategies like one proposed in the UK to abandon second doses as a way of speeding the process and husbanding scarce vaccine, or the way some countries are hoarding vaccine while others go without (potentially letting the virus, and variants, circulate and evolve freely).’

Read here (Wired, Mar 1, 2021)

To beat Covid, we may need a good shot in the nose

‘Intranasal vaccines might stop the spread of the coronavirus more effectively than needles in arms...

‘Although injected vaccines do reduce symptomatic COVID cases, and prevent a lot of severe illness, they may still allow for asymptomatic infection. A person might feel fine, but actually harbor the virus and be able to pass it on to others. The reason is that the coronavirus can temporarily take up residence in the mucosa—the moist, mucus-secreting surfaces of the nose and throat that serve as our first line of defense against inhaled viruses. Research with laboratory animals suggests that a coronavirus infection can linger in the nose even after it has been vanquished in the lungs. That means it might be possible to spread the coronavirus after vaccination.

‘Enter the intranasal vaccine, which abandons the needle and syringe for a spray container that looks more like a nasal decongestant. With a quick spritz up the nose, intranasal vaccines are designed to bolster immune defenses in the mucosa, triggering production of an antibody known as immunoglobulin A, which can block infection. This overwhelming response, called sterilizing immunity, reduces the chance that people will pass on the virus.’

Read here (Scientific American, Mar 1, 2021)

FLCCC to Merck: The data shows ivermectin's strong efficacy against Covid-19

‘The Front Line COVID-19 Critical Care Alliance (FLCCC) has issued a public statement in response to a press release recently issued by Merck.

‘The FLCCC Alliance reports that the Merck release of February 4, 2021— which concluded that there was no meaningful evidence for the clinical efficacy of ivermectin in patients with COVID-19 disease — did not provide any scientific data or analyses by Merck to support their conclusion.

‘Dr. Pierre Kory, President and Chief Medical Officer of the FLCCC said that, "The company's disregard for the most current medical evidence is an evidentiary indictment of their uncorroborated position. Merck's press release will cause governments, health authorities, medical providers, business leaders, and citizens to retreat from pursuing a medical agent that, according to our recent peer-reviewed and accepted publication to the highly regarded Frontiers in Pharmacology, has been proven to be an effective and globally available agent to prevent and treat every phase of COVID-19 disease."

Read here (PRWeb, Feb 16, 2021)

Common asthma drug cuts Covid-19 hospitalisation risk, recovery time: Oxford study

‘A commonly used asthma treatment appears to reduce the need for hospitalisations as well as recovery time for COVID-19 patients if given within seven days of symptoms appearing, researchers at the University of Oxford said on Tuesday (Feb 9).

‘The findings were made following a mid-stage study of the steroid budesonide, sold as Pulmicort by AstraZeneca and also used for treating smoker's lung.

‘The 28-day study of 146 patients suggested that inhaled budesonide reduced the risk of urgent care or hospitalisation by 90 per cent when compared with usual care, Oxford University said.’

Read here (Channel News Asia, Feb 10, 2021)

Four principles for urgent pharma action to combat Covid-19

‘Collaboration is needed between pharmaceutical companies and governments to combat the spread of COVID-19 and accelerate access to tests, treatments and vaccines. Norway, which co-chairs the Facilitation Council of the ACT-Accelerator, is committed to ensuring the global vaccination effort is managed effectively. Here are four principles which could ensure equitable access to COVID-19 tools and health products, particularly for low and middle-income countries:

• Principle 1: File for registration rapidly, widely and on the basis of the most rigorous standards
• Principle 2: Price health technologies fairly
• Principle 3: Expand production and supply capacity
• Principle 4: Transparency

Read here (World Economic Forum, Feb 9, 2021)

Inhaled budesonide in the treatment of early Covid-19 illness: A randomised controlled trial

Background Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness.

Methods We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.

Results 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care.

Conclusion Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.

Evidence before this study The majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed.

Added value of this study In this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care.

Implications of all the available evidence The STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.

Read here (Medrxiv, Feb 8, 2021)

Approve Ivermectin as Plan B for vaccination

‘On Jan 22, it was announced that the Ministry of Health (MOH) would be conducting clinical trials for two medicines, Ivermectin and Favipiravi, to determine their efficacy in treating Covid-19. Health Director-General Tan Sri Dr Noor Hisham Abdullah has acknowledged that Ivermectin "is cheap, easily available and safe for use." But in Malaysia, it is only licensed for use in animals...

‘In view of the worsening case on Covid-19 infections in our country, many unanswered questions and lack of data on the long term safety aspects of the Pfizer experimental mRNA vaccine (which our country has already been ordered) and the current production problems faced by vaccine manufacturers overseas (with the possibility of delays), the government here should have a "PLAN B".

‘It should quickly approve Ivermectin to provide a safe, cheap and effective "weapon" against Covid-19. The clinical trials by MOH on the efficacy of Ivermectin can continue but we should not need to wait (and let many more people suffer and die from Covid-19 in the meantime) since Ivermectin has ALREADY been PROVEN to be VERY SAFE over the last 30 years or so.

‘What have we got to lose by approving Ivermectin today in Malaysia as an option for doctors to prescribe against Covid-19?’

Read here (New Straits Times, Feb 7, 2021)

Experimental cancer drug could help hospitalised coronavirus patients recover within five days, Israeli trial claims

‘An experimental cancer drug could help hospitalised coronavirus recover quicker, researchers believe. Israeli academics today claimed 29 of 30 patients with moderate to severe case of Covid treated with EXO-CD24 made a full recovery within five days. 

‘Further human trials are now needed to prove that the inhaled drug - designed as a medication to fight ovarian cancer - actually works. The study did not compare the drug to a placebo, meaning scientists cannot say for certain that the medicine was behind the patients' speedy recovery.’

Read here (The Mail Online, Feb 5, 2021)

Merck statement on ivermectin use during the Covid-19 pandemic

‘Merck, known as MSD outside the United States and Canada, today affirmed its position regarding use of ivermectin during the COVID-19 pandemic. Company scientists continue to carefully examine the findings of all available and emerging studies of ivermectin for the treatment of COVID-19 for evidence of efficacy and safety. It is important to note that, to-date, our analysis has identified:

• No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies; 
• No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and; 
• A concerning lack of safety data in the majority of studies.

We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.

Read here (Merck press statement, Feb 4, 2021)