April 30, 2021

expert reaction to press release from Synairgen announcing data from their phase II trial of inhaled interferon beta in COVID-19 patients

Synairgen have published a press release today announcing the data from their phase II trial of inhaled interferon beta (IFN-beta) in COVID-19 patients.

Dr Penny Ward, Faculty of Pharmaceutical Medicine, Visiting Professor in Pharmaceutical Medicine, Kings College London, said:

“It’s tough doing community trials in viral respiratory illness and all too easy to make a potentially great drug look ineffective, as I know only too well!  The company have conducted a small study including older patients most of whom seem to have had pretty mild illness.  However the fact that the two subjects hospitalized were both in the placebo group suggests that a larger trial might be able to demonstrate some protection from disease deterioration, hospitalisation and death if treatment is started promptly.

“Regrettably, the press release does not provide sufficient data to enable an assessment of the baseline characteristics or the outcomes in the patient group as a whole or of the minority for whom more data is provided.  Inhaled beta interferon has previously shown prompt antiviral effect and protection of airways function in asthmatics with respiratory viral illness without impact on symptom severity due, potentially, to side effects from the treatment, some of which might have confounded the symptom scores used in this trial (ref: Am J Respir Crit Care Med. 2014 Jul 15;190(2):145-54. doi: 10.1164/rccm.201312-2235OC).

“As it stands, this study shows that patients can readily use the therapy at home and tantalisingly suggests that its use might reduce the frequency of hospitalisation after COVID infection.  We pressingly need additional community therapies for this disease as a ‘second string’ to vaccination.  Inhaled beta interferon could be one of these, but further work in a larger population, recruited earlier post first onset of symptoms and including additional evaluation of viral load as well as pattern of oxygen saturation and incidence of hospitalisation in the comparator and treatment groups will be needed to document/refute its potential.”

Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“The numbers are small.  Very small in the “post hoc analysis of” [a subgroup].  We are old that because the findings weren’t significant for the 120 patient cohort “We therefore decided to analyse the subset of patients with most severe symptoms.”

“Given the small numbers in the trials, the findings do not convince me.

“The natural history of Covid-19 disease is that viral replication is only a cause of illness in the initial stages; after that, severe illness is caused by an immune over-reaction initiated by the virus, but which continues well after the virus is no longer present.  The virus is seldom present for more than 10 days (often much less); and the breathing difficulties usually kick in at about 10 days.  Patients “with the most severe symptoms” are likely to be in the immune over-reaction phase of disease, which is not driven by the virus.  This means that the plausibility of benefit from an antiviral treatment (or one, like interferon-beta which enhances the antiviral response) is low.  Such treatments are unlikely, if the model of disease I’ve described is correct, to be of benefit in this stage of illness.

“Proving unlikely hypotheses requires much stronger evidence.

“Interferon-beta may possibly be of benefit at this stage of the illness, but given the lack of an obvious mechanism, given that at this stage the disease is no longer driven by the virus, I would prefer to see much data from a much larger study; and I would like to understand better the proposed mechanism of action.”

https://www.synairgen.com/umbraco/Surface/Download/GetFile?cid=299a7ec5-83b8-4b37-802a-0b55bcdc00e6

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

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.  Until July 2019 I was Chief Medical Officer of Virion Biotherapeutics, which was a company developing broad spectrum RNA therapy for the treatment/prevention of respiratory virus infections.  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).”

Dr Peter English: “No conflicts of interest.”