New Delhi: A “subtle push” is being given to remdesivir (RDV) as a treatment for Covid-19 while hydroxychloroquine (HCQ) is being “snubbed” despite the two drugs showing similar results with respect to coronavirus, a group of researchers has said.
The observations have been made by Dr Sumit Dang of the from University of Kentucky, US, Dr Amit Dang, founder and CEO of the Telangana-based MarksMan Healthcare, and Dr Vallish B.N., senior consultant at MarksMan Healthcare, in an analysis published in the peer-reviewed Indian Journal of Medical Ethics (IJME).
The IJME is India’s only journal on bioethics and medical ethics, and is published by the Forum for Medical Ethics Society (FMES), a Mumbai-based non-profit. MarksMan Healthcare is a scientific research consultancy and data analytics firm.
According to the researchers, HCQ appears to be courting greater scrutiny with respect to safety and efficacy, and risks associated with the much more expensive remdesivir seem to be getting played down.
The fact that this may be driven by “political affiliation, profiteering, and other conflicts of interest cannot be ruled out at this stage”, they say in an article titled “Hydroxychloroquine and Remdesivir (RDV) in COVID-19: A critical analysis of recent events” and published in the July-September print issue of the quarterly journal.
“Criticism of HCQ has been focused on safety (increased risk of adverse events and arrhythmias), followed by efficacy (lack of clinical or mortality benefit). However, there has been no acknowledgement of the high dose of HCQ given [during trials] when compared to the lower dose recommended by the Indian Council of Medical Research (ICMR),” they write.
“On the other hand, the lack of mortality benefit with RDV is being downplayed, and attempts to highlight a lack of new safety risks, despite observations to the contrary, are repeatedly made. It appears as if HCQ is being more closely scrutinised when compared to the lighter treatment given to RDV,” they add.
The researchers admit that the “widespread (mostly unsupervised) use of HCQ for other indications may have contributed to these unequal levels of scrutiny”, but add that “confounders such as political affiliation, profiteering, and other conflicts of interest cannot be ruled out at this stage, with the available evidence and information”.
Old vs new
As things stand, no drug has been conclusively proved to be effective in either preventing or treating Covid-19. However, some drugs have received emergency-use authorisations on the basis of preliminary studies and some anecdotal evidence.
Remdesivir and HCQ are two such drugs. While HCQ has been in use for around 80 years — for malaria, among other things — remdesivir is a product of this decade.
It was developed for the Ebola epidemic that hit three African nations in 2014-16, but was shelved after it was found to be less effective than alternatives. It has since been an experimental drug.
“The safety profile of HCQ is well-known since it has been in use for various other conditions as well. On the other hand, RDV has not been in long-term use for any other condition, and lacks a clear safety profile,” the researchers note.
“Analysis of various studies available at present does not prove a clear and conclusive efficacy benefit for either RDV or HCQ in clinical trials,” it says, citing links to research.
“It appears that a subtle push is being given to RDV, the safety of which is not adequately established; while HCQ is being subtly snubbed, despite both drugs having similar efficacy patterns.”
This, the researchers say, appears to be in “contravention of the basic ethical principles of beneficence, non-maleficence, autonomy, and justice”.
One of the studies cited was an 11 June paper looking into the compassionate use of remdesivir among severe Covid-19 patients, published by the New England Journal of Medicine.
“RDV administration was associated with adverse events in 32 out of 53 (60.3 per cent) patients, which included liver enzyme elevation and renal impairment in 12 and 4 patients respectively. Four patients discontinued RDV treatment prematurely. Despite this, the authors concluded that there were no new safety signals of concern,” the analysis states.
The researchers note that the “EUAs (emergency-use authorisations) of both HCQ and RDV do not contain any significant information about the safety aspect of the drugs”, but claim “anticipatory management of known safety risks is better than managing the adverse effects of a drug with an unknown safety profile”.
‘Toxicity, price difference’
The safety profile of remdesivir among Covid-19 patients has not been adequately studied in a sufficiently large number of patients, the researchers state.
The authors note that the number of patients who have received HCQ for Covid-19 in trials reported so far is larger than the number of patients who “received RDV for the same indication”.
“Also, HCQ has been documented to be safe during pregnancy. Due to considerations of lower toxicity and cost, HCQ was endorsed for usage in Covid-19 therapy. A lower dose HCQ for prophylaxis of Covid-19 was also proposed,” they say.
The authors also point to the cost difference between the two drugs. Quoting estimates from the Institute for Clinical and Economic Review, a US-based non-profit, they say a 10-day course of remdesivir could cost up to $4,500 (Rs 3,37,500), as compared to a production cost of $10 (Rs 750).
In contrast, they note, HCQ is cheaper by a wide margin (a pack of 10 tablets can be bought in India for around Rs 60).
“Favouring the expensive RDV over an inexpensive HCQ in treating Covid-19 might have significant implications in countries like India where a large proportion of medical expenditure is spent out-of-pocket.”