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)

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)

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)

Sinovac Covid-19 vaccine appears safe, triggers antibodies in trial in children: Researcher

‘Sinovac Biotech's Covid-19 vaccine appears to be safe and able to trigger immune responses among children and adolescents, according to preliminary results from early and mid-stage trials, the company said late on Monday (March 22). The preliminary data was from Phase I and II clinical trials involving over 500 people between the ages of three and 17 who received two shots of either medium or low dosage of vaccine, or a placebo. Most adverse reactions were mild, Zeng Gang, a researcher with the company, told an academic conference in Beijing.’

Read here (Straits Times, Mar 23, 2021)

Why you can't compare Covid-19 vaccines

‘In the US, the first two available Covid-19 vaccines were the ones from Pfizer/BioNTech and Moderna. Both vaccines have very high "efficacy rates," of around 95%. But the third vaccine introduced in the US, from Johnson & Johnson, has a considerably lower efficacy rate: just 66%.

‘Look at those numbers next to each other, and it's natural to conclude that one of them is considerably worse. Why settle for 66% when you can have 95%? But that isn't the right way to understand a vaccine's efficacy rate, or even to understand what a vaccine does. And public health experts say that if you really want to know which vaccine is the best one, efficacy isn't actually the most important number at all.’

View here (Vox, Youtube, Mar 20, 2021)

Moderna begins study of Covid-19 vaccine in kids

‘Moderna Inc has begun dosing patients in a mid-to-late stage study of its COVID-19 vaccine, mRNA-1273, in children aged six months to less than 12 years, the company said on Tuesday (Mar 16). The study will assess the safety and effectiveness of two doses of mRNA-1273 given 28 days apart and intends to enrol about 6,750 children in the United States and Canada.’

Read here (Channel News Asia, 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)

As the world vies for vaccines, Cuba’s making its own

‘Cuba may be on the verge of a coronavirus vaccine breakthrough and not a moment too soon, as deaths and cases spike on the communist-run island.

‘Starting in March, two of the island's four homegrown vaccine candidates will begin their third and final trials, the Cuban government has announced. While other developing countries compete with richer nations for a limited supply of doses, Cuba has gambled everything on producing their own vaccines, as much an exercise in national pride as a response to a public health crisis.’

Read here (CNN, Mar 3, 2021)

US National Institutes of Health launch new initiative to study “Long Covid”

Some of the initial underlying questions that this initiative hopes to answer are:

• What does the spectrum of recovery from SARS-CoV-2 infection look like across the population?
• How many people continue to have symptoms of COVID-19, or even develop new symptoms, after acute SARS-CoV-2 infection?
• What is the underlying biological cause of these prolonged symptoms?
• What makes some people vulnerable to this but not others?
• Does SARS-CoV-2 infection trigger changes in the body that increase the risk of other conditions, such as chronic heart or brain disorders?

These initial research opportunities will support a combination of ongoing and new research studies and the creation of core resources. We anticipate subsequent calls for other kinds of research, in particular opportunities focused on clinical trials to test strategies for treating long-term symptoms and promoting recovery from infection.

Read here (NIH, Feb 23, 2021)

Why kids need their own Covid-19 vaccine trials

‘Adolescents are being tested now. Younger children will be next. Why did vaccine manufacturers wait to study them?...

‘The U.S. Food and Drug Administration requires that new vaccines be independently studied in children. Children’s immune systems are still maturing and are unpredictable, so they might react to the coronavirus differently or have side effects that don’t occur in adults. “They might respond better or worse,” says James Campbell, professor of pediatrics at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health. “Until you do the study with the vaccine, you don’t know what will happen.”

Read here (National Geographic, Feb 20, 2021)

Oxford University to test Covid-19 vaccine response among children for first time

‘The University of Oxford has launched a study to assess the safety and immune response of the Covid-19 vaccine it has developed with AstraZeneca in children for the first time, it said on Saturday (Feb 13).

‘The new mid-stage trial will determine whether the vaccine is effective on people between the ages of 6 and 17, according to an emailed statement from the university. Around 300 volunteers will be enrolled and first inoculations are expected this month, Oxford said.’

Read here (Straits Times, Feb 13, 2021)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘It is important to note that all the severe Covid-19 cases were in the placebo group, which suggests that mRNA-1273 is likely to have an effect on preventing severe illness, which is the major cause of health care utilization, complications, and death. The finding of fewer occurrences of symptomatic SARS-CoV-2 infection after a single dose of mRNA-1273 is encouraging; however, the trial was not designed to evaluate the efficacy of a single dose, and additional evaluation is warranted.

‘Overall, the safety of the mRNA-1273 vaccine regimen and platform is reassuring; no unexpected patterns of concern were identified. The reactogenicity associated with immunization with mRNA-1273 in this trial is similar to that in the phase 1 data reported previously. Overall, the local reactions to vaccination were mild; however, moderate-to-severe systemic side effects, such as fatigue, myalgia, arthralgia, and headache, were noted in about 50% of participants in the mRNA-1273 group after the second dose. These side effects were transient, starting about 15 hours after vaccination and resolving in most participants by day 2, without sequelae.’

Read here (New England Journal of Medicine, Feb 4, 2020)

Efficacy of colchicine in non-hospitalized patients with Covid-19 (pre-print)

Background Evidence suggests the role of an inflammatory storm in COVID-19 complications. Colchicine is an orally administered, anti-inflammatory medication beneficial in gout, pericarditis and coronary disease.

Methods We performed a randomized, double-blind trial involving non-hospitalized patients with COVID-19 diagnosed by polymerase chain reaction (PCR) testing or clinical criteria. The patients were randomly assigned to receive colchicine (0.5 mg twice daily for 3 days and once daily thereafter) or placebo for 30 days. The primary efficacy endpoint was the composite of death or hospitalization for COVID-19.

Results A total of 4488 patients were enrolled. The primary endpoint occurred in 4.7% of the patients in the colchicine group and 5.8% of those in the placebo group (odds ratio, 0.79; 95.1% confidence interval (CI), 0.61 to 1.03; P=0.08). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 4.6% and 6.0% of patients in the colchicine and placebo groups, respectively (odds ratio, 0.75; 95% CI, 0.57 to 0.99; P=0.04). In these patients with PCR-confirmed COVID-19, the odds ratios were 0.75 (95% CI, 0.57 to 0.99) for hospitalization due to COVID-19, 0.50 (95% CI, 0.23 to 1.07) for mechanical ventilation, and 0.56 (95% CI, 0.19 to 1.66) for death. Serious adverse events were reported in 4.9% and 6.3% in the colchicine and placebo groups (P=0.05); pneumonia occurred in 2.9% and 4.1% of patients (P=0.02). Diarrhea was reported in 13.7% and 7.3% in the colchicine and placebo groups (P<0.0001).

Conclusion Among non-hospitalized patients with COVID-19, colchicine reduces the composite rate of death or hospitalization. (COLCORONA ClinicalTrials.gov number: NCT04322682)

Read here (Medrxiv, Jan 26, 2021)

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe Covid-19: A pilot, double-blind, placebo-controlled, randomized clinical trial

Added value of this study: ‘This pilot, randomized, placebo-controlled, double blind trial failed to show a reduction in the proportion of PCR-positive patients seven days after ivermectin treatment; yet it shows a reduction in the self-reported anosmia/hyposmia and a (non-statistically significant) tendency to lower viral loads and lower IgG titers which presumably reflect milder disease.’

Implications of all the available evidence: ‘The positive signal found in this pilot together with emerging evidence from animal models and other clinical trials warrants the conduction of larger trials using ivermectin for the early treatment of COVID-19.’

Read here (EClinicalMedicine, The Lancet, Jan 19, 2021)

A second Chinese coronavirus vaccine is said to be effective

‘Brazilian officials said Thursday that a coronavirus vaccine made by a Chinese company was effective, bolstering the chances of approval for a second Chinese inoculation that could be rolled out in much of the developing world. Officials in the state of São Paulo, where a prominent medical research institute carried out a large study of the vaccine made by the Beijing-based Sinovac, said the inoculation had an efficacy rate of 78 percent.

‘The vaccine prevented all participants from developing serious and mild complications from the virus, officials said, calling it a highly effective preventive tool. Sinovac Biotech has sold more than 300 million doses to the developing world, filling a gap left by Western countries.’

Read here (New York Times, Jan 7, 2021)

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

‘Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

‘Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

‘Results: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

‘Conclusions: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19.’

Read here (NCBI-New England Journal of Medicine, Jan 6, 2021)

India’s push to use untested vaccine rings alarm bells

‘India’s need for speed in providing a Covid-19 vaccine and attempts to push a locally-produced version through for use before a required phase 3 trial was finished has raised doubts and protests from politicians, scientists and academicians.

‘The Drugs Controller General of India (DCGI) approved the Oxford-AstraZeneca vaccine that’s being produced locally by the Serum Institute of India as Covishield. The world’s largest vaccine manufacturer based in Pune said it can readily provide 50 million vaccines to the government for immediate use and can roll out full production to start supplying the population by March.

‘The DCGI also approved a vaccine produced by Bharat Biotech Ltd along with the Indian Council for Medical Research and the National Institute of Virology named Covaxin for emergency use on a trial basis.’

Read here (Asia Times, Jan 4, 2020)

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data

Peter Doshi: Pfizer and Moderna’s “95% effective” vaccines—we need more details and the raw data 

‘Five weeks ago, when I raised questions about the results of Pfizer’s and Moderna’s covid-19 vaccine trials, all that was in the public domain were the study protocols and a few press releases. Today, two journal publications and around 400 pages of summary data are available in the form of multiple reports presented by and to the FDA prior to the agency’s emergency authorization of each company’s mRNA vaccine. While some of the additional details are reassuring, some are not. Here I outline new concerns about the trustworthiness and meaningfulness of the reported efficacy results...’

Read here (BMJ, Jan 4, 2021) 

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine (Pfizer clinical trial)

BACKGROUND: ‘Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.’

METHODS: ‘In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.’

RESULTS: ‘A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.’

CONCLUSIONS: ‘A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 31. 2020)

Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

‘This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.

‘The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline... 

‘The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427. opens in new tab.)’

Read here (New England Journal of Medicine, Dec 30, 2020)