Favipiravir Approval for COVID in India: Docs Share Their Concerns

What do we know about the drug and what research is the approval based on? FIT explains.

Updated
Coronavirus
5 min read
What do we know about the drug and what research is the approval based on? FIT explains.
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Glenmark Pharmaceuticals on Saturday, 20 June, launched antiviral drug Favipiravir for the treatment of mild-to-moderate COVID-19 cases after receiving ‘restricted emergency’ approval from the Drug Controller General of India to manufacture and market the medicine.

“The approval has come at a time when cases in India are spiralling, putting tremendous pressure on our healthcare system.”
Glenn Saldanha, Chairman and Managing Director of Glenmark Pharmaceuticals

What do we know about the drug and what research is the approval based on? FIT explains.

What is Favipiravir?

The antiviral drug Favipiravir is approved in Japan since 2014 for the treatment of novel or re-emerging influenza virus infections. It works by inhibiting viral replication and reducing the viral load in a patient.

It is an experimental medicine being repurposed for COVID-19.

The drug FabiFlu will be available as a prescription-based medication for Rs 103 per tablet, with the recommended dose being 1800 mg twice daily on day 1, followed by 800 mg twice daily up to day 14.

Informed consent of the patient will have to be taken in the prescribed form by the treating physician before administering the medicine.

The drug is not recommended in patients with severe renal, hepatic impairment, and in pregnant and lactating women.

What Does Research Say?

Glenmark was the first company in India to receive the drug regulator's approval to conduct phase-3 clinical trial of Favipiravir antiviral tablets for COVID-19 patients.

The company has claimed that Favipiravir shows clinical improvements of up to 88% in COVID-19 disease, with a rapid reduction in viral load by 4 days.

A randomized multi-centric study was initiated in 150 patients in India to evaluate the efficacy and safety of the drug used with standard care in comparison to the group that received only supportive care. The study’s details are yet to be published in a peer-reviewed paper.

Glenmark has referred to four studies to substantiate the drug’s efficiency; A Russian clinical trial, an observational study in Japan on over 2,000 patients and two Chinese studies that compared it with antiretroviral drugs, finding it safer and faster in reducing time to relief than antiviral umifenovir.

Favipiravir is being studied in at least 18 trials around the world as a potential treatment for COVID-19. Glenmark had also announced that it is conducting another clinical trial to evaluate the efficacy of two antivirals Favipiravir and Umifenovir as a combination therapy in moderate hospitalized adult COVID-19 patients in India.

Insufficient Evidence, No Real Requirement: Doctors

Dr Manoj Goel, Director, Pulmonology, Fortis Memorial Research Institute, tells FIT, “There are several issues here. It’s an experimental drug for which we don’t have much evidence. If you also look at the recommended dosage, it amounts to too many tablets over the course of 14 days. And most importantly, the section of infected people it is being advised for - those with mild or moderate illness - have a high chance of recovery even otherwise. They will anyway recover.”

In conversation with FIT, Dr Sumit Ray, a critical care specialist in Delhi also pointed towards the weak evidence and the fact that there is no actual need for a specific antiviral drug for mild to moderate COVID patients.

“For a medicine to be truly helpful in COVID management, it needs to show its effect in any of the following ways: by reducing mortality in patients, by bringing down the number of days a person spends in the ICU, by reducing the number of people who need a ventilator or by inhibiting the progression of the disease from a mild to critical illness. If it doesn’t do that, its use is questionable.”
Dr Sumit Ray

“The most damage that the disease causes is in the way it triggers the immune response in critical patients or the body’s clotting ability. The drug doesn’t help improve any of these real outcomes of COVID-19. So how does it really benefit? Most of the mild patients will recover anyway. Such medicines based on poor quality studies would just end up putting pressure on doctors. Families will get desperate to ask for the prescription even when there is no need and despite the risk of side-effects that accompanies any drug,” he says.

Dr Sahaj Rathi, hepatologist and researcher, and Dr SP Kalantri, Professor of medicine and medical superintendent, MGIMS Sevagram, shed light on the lack of randomized controlled trials (RCT) and the insufficient data to establish any benefit of the drug for COVID-19 treatment. “For any drug to be approved for widespread clinical use, there has to be a proof of safety and efficacy. The best way to know that is through randomized controlled trials (RCT) in which every participant has the opportunity to be given or not given the drug. All things being equal, the benefit, as well as side-effects of the drug, can be estimated.”

“Had there been a suggestion of overwhelming benefit from Favipiravir, a rapid provisional approval could have been justified. The problem here is that not a single RCT anywhere in the world has yet been completed on this drug in COVID-19 patients. The only ‘proof’ is a small, unrandomized Chinese study where Favipiravir was given to 35 people with mild disease only, and there was no objective improvement in clinically relevant parameters. Moreover, it was published in a journal ‘Engineering’, which is not even a standard medical journal.” 
Dr SP Kalantri and Dr Sahaj Rathi

There is an RCT being conducted by Glenmark, but it is still ongoing, they add.

“This is a finite disease which culminates in either death or complete recovery, and the outcome is clear by day 28 in most cases. For the approval of this drug for public use, there has to be unequivocal evidence of safety and efficacy-either prevention of death or shortening of ICU stay. Anything short of that is inadequate.”
Dr SP Kalantri and Dr Sahaj Rathi

“Yes, these are desperate times, and we are all looking for a ray of hope. But wishful thinking does not make an untested drug effective. Abandoning scientific reasoning would only give transient hope, and may actually be detrimental in the long run. On the other hand, rapidly conducted trials would give us at least workable evidence to go on. The argument that trials cannot occur during a pandemic is invalid, as is clearly shown by the many trials published from across the world,” they add.

The Economics and Financial Strain

Dr Kalantri and Dr Rathi also point towards the unnecessary expense that the use of this medicine could lead to for patients who would have a high chance of recovery even without it.

“The total cost of the entire drug regimen lasting 14 days would amount to around Rs 15,000. How is it fair to subject people with mild disease, most of whom would recover on their own, to an expensive medicine with no proven benefit?”
Dr SP Kalantri and Dr Sahaj Rathi

“This would create pressure and guilt among families of COVID-19 patients, who would be forced to arrange for the medicine due to the illusion of its efficacy.”

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