As Vaccine Trials End, Where Do Covid-19 Treatments Stand?

New Delhi, 24 Nov 2020:

Vaccine developers have been racing against time to find a shot that offers immunity against the coronavirus disease (Covid-19). The University of Oxford announced on Monday that its vaccine against the viral disease was up to 90% effective in preventing infection, Pfizer Inc. filed for emergency use authorization in the US for its vaccine that showed 995% efficacy last Friday, Moderna said its vaccine was 94.5% effective, even as Hyderabad-based Dr Reddy’s Laboratories got ready to begin late stage trails of Russia’s Sputnik V in India this week. Parallelly, major treatment protocols are being revised following results from several global trials that cleared the air on which Covid-19 therapies work better than others.

Most Covid-19 treatments fall under three broad categories, antivirals that prevent the virus from multiplying, immune-modulators that regulate the immune response, and combinations that use multiple mechanisms of action.

Antiviral remdesivir

The antiviral remdesivir was suspended from the World Health Organization prequalification list that developing countries use as a benchmark for procurement. The suspension followed the health agency’s guidance on Friday against the use of remdesivir in hospitalized patients, regardless of disease severity, after an international guidelines development group found no evidence that the drug improves survival rates, reduces the need for mechanical ventilation, or boosts recovery and other patient outcomes. The group, however, recognized that more research was needed, and supported continued enrolment in trials evaluating remdesivir.

“The guidelines group of WHO is separate from Solidarity Trial group as it reviews all evidence, including the WHO trial. They have concluded that there is no evidence of benefit from (remdesivir) in any group of hospitalised patients and that available evidence is inadequate if there is a benefit in non-hospitalised patients. As such, corticosteroids are the only class of drugs with demonstrated benefit on reducing deaths in hospitalised patients. The search for other effective modalities of treatment goes on,” said Dr K Srinath Reddy, president, Public Health Foundation of India.

Aspirin and other anti-coagulants

On the upside, the ubiquitous painkiller and blood-thinning drug aspirin was added to the UK’s Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial in early November. “Clotting is a big problem [in Covid-19]. Aspirin is a widely available, cheap drug which, if it were to work, would be a huge boost,” Peter Horby, the chair of the RECOVERY trial and professor of emerging infectious diseases and global health at the University of Oxford, told joint inquiry committees from the House of Commons in the UK.

“We’re [also] seeing better use of anticoagulants — heparin and others — to prevent clotting, and one would anticipate that the introduction of dexamethasone has also had an impact. That would be something that would reduce fatality rates,” said Horby.

Monoclonal antibodies

The US Food and Drug Administration this month issued an emergency use authorisation for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate Covid-19 in adult and paediatric patients who are 12 years of age and older weighing at least 40 kg who are at high risk for progressing to severe disease and/or hospitalization. Bamlanivimab is not authorized for patients who are hospitalized or need oxygen therapy as it may worsen clinical outcomes.

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight harmful antigens, such as viruses and bacteria. Bamlanivimab is directed against the spike protein of Sars-CoV-2, the virus that causes COvid-19, and works by stopping the virus from entering human cells.

The US National Institute of Allergy and Infectious Diseases’ ACTIV-5 Big Effect Trial also began trials of the monoclonal antibodies risankizumab and lenzilumab last month to determine whether they helped hospitalized patients recover faster.

Some trials fell short. In October, Eli Lilly and Regeneron Pharmaceuticals suspended their trials of monoclonal antibodies in hospitalised patients on the grounds of lack of efficacy and potential safety concerns.

Monoclonal antibodies are approved for Covid-19 treatment in India. “Monoclonal antibodies have some role in early disease, but not in patients who are on oxygen or ventilator support. Since they have a limited role in mild disease, and we know a large number of patients recover on their own, they may not really benefit that much,” said Dr Randeep Guleria, director, All India Institute of Medical Sciences (AIIMS) Delhi at HT Leadership Summit on Thursday. “We also have to consider whether we will have enough doses to offer everyone, whether the cost can be met as they are expsnsive, and whether they will be needed once the vaccines come,” said Guleria.

Anti-parasitic ivermectin

Studies have shown that the affordable and widely available drug ivermectin used to treat parasitic infections has antiviral action against the Sars-CoV-2. The use of ivermectin in doses ranging from 200 to 1200 mcg/kg body weight, for a duration of three to seven days, is showing promise in symptomatic relief and viral load reduction.

Two studies of ivermectin alone or in combination with doxycycline, found ivermectin-doxycycline combination therapy had a better success of symptomatic relief, shortened recovery duration, reduced adverse effects, and superior patient compliance compared to the hydroxychloroquine-azithromycin combination in mild to moderate cases of Covid-19 disease. A retrospective study of 280 patients treated with ivermectin against standard of care found fewer deaths in the ivermectin group.

In India, ivermectin is part of at least five ongoing trials, according to Clinical Trials Registry India, and its benefits are under review.Hindustan Times