‘Molnupiravir has the potential to treat patients with early stages of SARS CoV 2’

A paper by Professor Vyas Shingatgeri, Dean, School of Biosciences, Apeejay Stya University, and Professor Ashok Rattan suggests that the oral anti-viral drug Molnupiravir can be used to treat patients with early stages of SARS CoV 2. However, we must be both cautious and watchful while using the same and should never be used in patients less than 18 years of age. In an interview, Professor Vyas Shingetgeri strikes a note of caution and says that we must be cautious while using Molnupiravir in treating early stages of SARS CoV 2 but at the same time we should not lose sight of the fact that a five-day course of Molnupiravir together with booster doses and Covid-appropriate behaviour has the potential to bring this pandemic to an end. Edited excerpts:

Please tell us how you thought of writing this paper on the use of Molnupiravir in early Covid-19 infection and whether it is a chance to end the pandemic?

First of all let me tell you the idea to write something on Molnupiravir occurred to me during discussions with my ex-colleague in Ranbaxy Laboratories Limited; Dr Ashok Ratan, who is an eminent Medical Microbiologist from AIIMS and has worked as Lab Director CAREC managed by PAHO/WHO, about the apprehensions of use of Molnupiravir to treat Covid-19 by ICMR, especially in their recommendations to Ministry of health.

They did not include this drug in their recommendations to the health ministry for the treatment of Covid on the grounds of its toxicity although it has been approved by USFDA, UK MHRA and DCGI. Based on the clinical trials; though limited and the data that has been published on its efficacy, it seems to be a very effective drug against SARS COV 2 if treated at the early stages (as soon as it is detected). During this time it so happened that I had been going through a lot of messages on WhatsApp by my colleagues and friends about this drug and it being very toxic and why it should not be taken. Some of my family friends who were detected with Covid-19 were also apprehensive about using such a medicine when I discussed with them and asked them to get an appointment with a pulmonologist. Some of the doctors did prescribe Molnupiravir and others did not and hence many of my friends and relatives were apprehensive to consume and some people discouraged them on the basis of what was read by them in the newspapers especially when ICMR submitted their recommendations. We spoke to a few doctors (MD-Internal Medicine) and pulmonologists and discussed with them the data that we perused from the literature and the data that was available through freedom of information on the FDA site and the papers. We felt that it was essential to remove the fear that existed in the mind and rather than entering in to a situation of complication (getting localised in the lungs) if not treated early while it is in the upper respiratory tract, especially the major signs of Omicron was in the upper respiratory tract though few patients did reveal breathlessness. Even some of my close relatives, for instance my brother, sister-in-law, sister and my brother-in-law in Mumbai, who were detected with Covid-19 had similar symptoms. When they spoke to doctors treating them and were prescribed this medicine, followed the instructions of the doctors and hence were asymptomatic within seven days and returned to normal and on 10th day were negative when RTPCR was done. While none had any side effects that were manifested we further believed that awareness must be created and hence we just tried our best to put forth in the best possible way the risk associated versus the benefit and how the pandemic can be tamed. This is our own perspective and we have seen doctors now prescribing it.

Has it been published in any medical or peer reviewed journal?

No, we did not submit it for publication to any journal. The idea was to make people aware and that is why we put it directly on LinkedIn. The timing was crucial. It was also when the ICMR made recommendations to the ministry of health and the apprehension was growing for making use of this drug. Now what I understand and know is that many of the doctors are prescribing it.

According to you, how effective can Molnupiravir be against the fast spreading Omicron variant?

If you are positive and if you begin treatment with Molnupiravir within the first three days of being diagnosed, it is quite effective. Though the efficacy data from the limited clinical trial suggest good efficacy approximately between 3 to 30% but it is better to reduce the viral load in the earlier stages so as to reduce the post-viral complications once it reaches to pulmonary tissue and current usage has shown that people have been showing better results and are getting free of their symptoms and thus reduction in the spread of the disease too. As I’ve said above we have many examples of those who have been treated, in our institute, including my family members and many other friends and colleagues who have been treated with Molnupiravir when given as soon as the disease was detected. Further based on the Phase III clinical trials; the clinical profile of Molnupiravir has demonstrated a significant reduction in the risk of hospitalisation or death with no observed safety concerns when compared to the placebo group. If used among the elderly and unvaccinated individuals with comorbidities immediately after the diagnosis it can certainly help reduce the viral load to a greater extent and thus has greater benefits compared to the risk associated.

Molnupiravir has been authorised for use in more than 10 countries, including the US, UK and Japan for patients who are more than 45 -50 years of age. What is its status vis-a-vis Indian health and drug regulatory bodies?

The CDSCO panel recommends restricted emergency use of Molnupiravir and what this means is they have approved it for the treatment of adult patients with Covid-19, with SpO2 > 93% and who have high risk of progression of the disease including hospitalisation or death and this clearly sounds a cautious approach and hence they are very cautious and as a regulatory body, the toxicity observed in the preclinical studies though at the higher doses cannot be overlooked.

You’ve mentioned the safety concerns of this compound are mainly because of its being mutagenic and having bone and cartilage toxicity. What are your views about its safety and efficacy?

To be specific, we would like to state the following.  During drug development all the safety concerns are being addressed by conducting appropriate preclinical safety/toxicity studies and in these preclinical studies (three months toxicity studies in rats) this drug-induced toxicity in bones and cartilages especially of the long bones was however noticed at very high doses and these doses are actually five times higher than the doses that are being considered in humans and similar toxicity in large animals were noticed at 19 times higher doses than human dose. The drug is definitely teratogenic and hence cannot be given to pregnant women.

Molnupiravir was found to be mutagenic in Ames assay (that’s carried out in prokaryotes- in bacterial cells). However it was neither clastogenic and did not induce the micronucleus and aberrations in any of the In Vitro and In Vivo assays. However, based on the entire genotoxicity data and the duration of the treatment (not more than 5 days), Molnupiravir has low risk for genotxicity as compared to the benefits of being used in the cases where it can save patients. Similar In Vitro toxicities were observed with fluroquinolone group of antibiotics and yet millions of doses have been used of Ciprofloxacin. Thus considering the duration of the treatment, the benefits associated with the treatment versus the risk associated if left untreated and the infection entering the pulmonary tissue we did not feel that this toxicity has much clinical concern.

Is there a trade-off between its efficacy and its safety?

If treated early and in the age group of 50 and above with symptoms its go ahead for the treatment as the efficacy safety window is good. The correct dose will be 800 mg twice a day for five days (4 Tabs of 200 mg tablets in the morning and 4 tabs in the evening ).

Your  write -up says while we must be both cautious while using Molnupiravir in treating early stages of SARS CoV 2 at the same time we should not lose sight of the fact that a 5-day course of Molnupiravir together with booster doses and Covid-appropriate behaviour has the potential to bring this pandemic to an end. What is your view on this?

By cautious we mean we must not use it in the case of youngsters especially below 18 years. We MUST use it for old patients and especially those who have not been vaccinated and have comorbidities.

It is not recommended during pregnancy? What is the reason behind this?

It is not recommended during pregnancy as its Teratogenic can cause birth defects in the foetus in the preclinical studies. No doctor will recommend it and it’s a prescription drug.

Have the ICMR’s safety concerns been addressed?

ICMR’s safety concerns are genuine based on the current data and hence it cannot be used by the patients directly but definitely after prescription by the doctor to the relevant population and the concerns shall gradually be evaded as the more and more data is being generated after its cautious use.