On Wednesday, the Indian Council of Medical Research (ICMR) gave thumbs down to Merck’s Molnupiravir, the antiviral drug that, only a fortnight ago, received approval for emergency use by the Drugs Controller General of India (DCGI).
India’s Covid-19 Task Force has not included Molnupiravir in its treatment protocol, further underscoring the differences in opinion between the Task Force and the country’s drug regulator.
ICMR Director General Professor Balram Bharagava, who is part of the Task Force, has been voicing safety concerns over the use of Molnupiravir. The ICMR chief is a part of the Task Force.
“Twelve clinical trials of Molnupiravir have been registered in India, all yet to begin,” Professor Balram Bhargava said.
Twice in two separate press briefings, the ICMR DG has voiced concerns about the drug, saying its harms outweigh the benefits. Professor Balram Bhargava has also said that there could be irrational use of the pill which received the DCGI’s nod on December 28.
‘Demonstrated reduction in risk of hospitalization in phase-3 clinical trial’
MSD/ Merck (Merck is known as MSD outside of the US and Canada) issued a statement on January 7 that read: “We are confident in the clinical profile of Molnupiravir, which demonstrated a significant reduction in the risk of hospitalization or death in our phase-3 clinical trial with no observed safety concerns when compared to the placebo group.
“Based on the strong science behind Molnupiravir – a single oral medicine that interrupts replication of the SARS-CoV-2 virus, with clinical data showing generally consistent efficacy across patients infected with variants of concern, Delta, Gamma, and Mu, and with preliminary preclinical data showing antiviral activity against Omicron – Molnupiravir has the potential to become an important tool for healthcare professionals and appropriate patients.
Molnupiravir has yet to be evaluated against Omicron in clinical studies,” the statement went on to add.
The decision not to include Molnupiravir in India’s Covid treatment protocol has prompted mixed reactions.
‘ICMR’s criticism is justified’
Dr SP Kalantri, Professor of Medicine at the Mahatma Gandhi Institute of Medical Sciences in Sevagram, told India Today that Molnupiravir, an oral drug against the Covid-19 virus, has generated a lot of hype and (unjustified) hope among the public.
Dr Kalantri says there is no data to support the drug and the ICMR’s criticism is justified.
“The clinical trial did not include those who had past Covid infection; none of the participants were vaccinated; pregnant and immunosuppressed individuals were excluded and the drug was not tested against the currently circulating variant (Omicron),” he added.
Dr Kalantri added, “Of note, its benefits are modest – 33 mild-moderately ill; at-risk adults need to be treated to stave off one Covid-related hospitalisation. The drug has not been shown to benefit diabetics and those with heart disease.”
He also says that the safety concerns are valid.
“The potential risk of mutagenic toxicity and genotoxicity is a matter of concern. Of concern is propaganda masquerading as drug marketing which makes the drug look much more powerful and safe than it really is. The ICMR is therefore fully justified in not including the drug in its Covid treatment protocol.”
‘ICMR chief’s comments are unreasonable’
Dr AK Singh, a practicing Endocrinologist at Kolkata’s GD Hospital & Diabetes Institute, says, “What is paramount is the selection of patients.”
Dr Singh is the principal author of a paper on Molnupiravir that has been peer-reviewed and published.
“Side-effects cited by the ICMR DG were seen in young animal toxicity/overdose studies and all of these were done in the USA,” Dr AK Singh said, adding that the ICMR Director’s comments are “unreasonable”.
Dr Singh also reiterated that the drug was approved by the US FDA (Food and Drug Administration) and CDSCO (Central Drugs Standard Control Organisation) followed suit. These side effects were not seen in human trials, Dr Singh adds.
Dr Singh told India Today, “Molnupiravir has only been studied in mild-to-moderate unvaccinated COVID-19 adult patients with at least 1 risk factor for progression to severe COVID-19. Therefore, one must limit its use only for these groups of patients.”
“Molnupiravir was not that effective in individuals with a past history of Covid-19 and it has not been studied in vaccinated individuals, therefore these findings must be taken into account. In any case, both these subsets of patients are no longer high-risk cases and hence may not be an indication for using Molnupiravir,” he added.
In his paper on the antiviral drug, Dr AK Singh wrote that the role of Molnupiravir in post-vaccinated breakthrough infections is not known and it was not effective in people with a past history of Covid-19, as per the paper.
Dr Singh’s findings also indicate that despite some concern in pre-clinical studies, a five-day course of Molnupiravir in adults and non-pregnant Covid-19 patients appeared to be safe and that the effectiveness of Molnupiravir is competitive to three monoclonal antibodies – Remdesivir and Nirmatrelvir and Ritonavir – with a relatively lower cost.
‘Discrepancy should not have surfaced to begin with’
But there are also many who question the approval process.
Malini Aisola, co-convener of the All India Drug Action Network (AIDAN) said that there is a demand for Molnupiravir because of the regulator’s approval. This discrepancy should not have surfaced, to begin with, she added.
“The CDSCO has to approve Covid drugs responsibly. This is not the first time it has approved drugs that are not included in the national guidelines, raising questions about the meaningfulness of the license. Several drugs that were given EUA [Emergency Use Approval] have not been reviewed and the approvals revoked even though data subsequently did not show any benefit,” Malini Aisola told India Today.
She added that this discrepancy shows a “mismatch between the regulator’s priorities in promoting pharma interests and the objectives of serving public health”.’Discrepancy should not have surfaced to begin with’. India Today