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The press release from AstraZeneca states that their long acting antibody combination, AZD7442, reduced risk of developing severe COVID-19 or death compared to placebo in non-hospitalised patients with mild-to-moderate symptomatic COVID-19.
Dr Kovilen Sawmynaden, Principle Scientist, LifeArc, said:
“It is really positive news that this antibody-based drug is able to both prevent and treat COVID-19 infections. With respect to therapy, it certainly adds new weaponry to our arsenal (after the recent approval of Ronapreve). However, it would be interesting to know if patient stratification is required. For example, how many patients were antibody-positive (or negative) prior to use of this antibody treatment?
“Direct-acting antivirals (such as Molnupiravir) may have some future advantage in the therapy space, particularly in terms of cost, route of administration and viral resistance. However, potent antibody combinations such as these do provide valuable tools for those patients in need of ‘instant immunity’ and/or in high-risk groups, who haven’t responded to vaccines. The modification of this antibody to provide a long-lasting effect is particularly welcome.”
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“I commented recently on the announcement about Merck’s molnupiravir therapy for Covid-19 infection.
“While the mechanism of action of antibodies, such as ZD7442, and antiviral agents like acyclovir, oseltamivir, or molnupiravir is different, they all act by attacking the virus. They therefore need to be given early, as they only work early in the early phase of the illness, while viral replication is still driving disease. If given later – when the virus has been eradicated and the illness is caused by an immune overreaction triggered by previous viral replication, they are unlikely to be of value: treatments (like dexamethasone) to control the inflammation and immune overreaction – are more important, as I have described elsewhere.1 2
“Because of this, such treatments have to be given not only early in the course of the disease, but – as severe disease is a late feature – before you know if the patient will be seriously ill or not. Indeed, ideally, so early that you may not have had time to confirm the diagnosis. As with molnupiravir, ZD7442 is most likely to be of value in people known to be at high risk who can be given the treatment early in the course of their illness.
“This means that any such treatments must also be:
“Whether all of these qualities apply to ZD7442 is not yet clear to me.”
References
Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at Kings College, London, said:
“Interesting data from the TACKLE trial using AZs combination monoclonal antibody IM injection AZD7442 to treat patients with symptomatic COVID and at least one factor making them at higher risk of severe disease. One IM injection of AZ7442 given within 7 days of symptom onset reduced the incidence of severe disease or death by 50%, and given within 5 days by 67%, once again confirming that treatment with an effective antiviral given as soon as possible after first onset of symptoms can reduce the risk of hospitalisation and death with effectiveness being inversely related to duration of symptoms prior to treatment.
“It is considerably simpler to give an IM injection than an IV infusion making this a suitable product for community deployment to reduce the burden of hospitalisations due to COVID on the NHS. Unlike oral medications monoclonal antibody treatments do not interfere with other medicines a patient may need to take for other conditions, which may potentially make administration simpler for these patients than some of the oral antiviral medicines which have more complex pharmacokinetics; the once and done approach is also attractive in ensuring that patients complete the course of treatment. This monoclonal antibody construct provides long lasting protection against reinfection/disease for up to 12 months and thereby may be a useful addition for immune-suppressed individuals whose response to vaccination is suboptimal.
“Although all patients with COVID could benefit from treatment, patients at particular risk of more severe disease including the elderly, those with cardiac and respiratory disorders, diabetes, cancer and immune suppression. Such a treatment may also help pregnant women who are at particular risk of more severe disease should they become infected. Well done to AZ – another significant contribution to the management of COVID and more help in making it a manageable disease.”
Declared interests
Dr Kovilen Sawmynaden: “LifeArc is a medical research charity. We were part of the BIA Antibody Taskforce to identify potential neutralising antibodies for Sars-Cov-2, donating our time and efforts on this project.”
Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody). These are my personal views and do not reflect those of either institution.”
None others received.