US President Donald Trump’s relentless promotion of the 86-year-old generic drug hydroxychloroquine, used successfully to treat malaria, lupus and rheumatoid arthritis, as an experimental treatment for COVID-19 continues to dominate the discussion in medical circles and in the media.

So far, the main consequence has been that the US Food and Drug Administration (FDA), despite initial reservations, has temporarily allowed the drug to be used for experimental treatment  – if it can be sourced at all amid speculative buying.

Clinical trials with the drug are now scheduled and will take months to complete. The US health watchdog, however, has allowed physicians to prescribe it and retail pharmacists to formulate it as tablets to dispense to patients who hope to find a place in clinical trials as well as those who don’t find a place.

The emergency approval requires only that doctors and patients have access to a fact sheet that outlines risks and interactions with other medications.

The FDA, under populist pressure, is basing its decision on what leading infectious diseases specialist and presidential advisor Anthony Fauci in a White House press briefing called anecdotal evidence. Only two small studies with COVID patients have been conducted, both by the same medical team and without a defined control group.

To conduct the trials, the US Department of Health and Human Services (HHS) has accepted donations of millions of tablets from the surplus stocks of international pharmaceutical producers including Bayer, Sandoz, Mylan and Amnael. Sanofi also produces a branded drug under the name Plaquenil, but it is not sold on the US market.

Despite the donations, both chloroquine and hydroxychloroquine are both short. Mylan has pledged to increase its production, and Sandoz parent Novartis has said it will search for more supplies.

Novartis CEO Vas Narasimhan told Swiss newspaper SonntagsZeitung  the company is “working with Swiss hospitals on possible treatment protocols for the clinical use of the drug, but it's too early to say anything definitively."

US officials also have beseeched India to lift its export ban for hydroxychloroquine. According to Bloomberg, Indian imports have a 47% share of the US market. The country, which is in the throes of a 21-day lockdown ordered by Prime Minister Narendra Modi and potentially faces a serious outbreak, reportedly has now agreed to license its stock to other “badly affected” countries.

French experiment is controversial

Trump has promoted especially the combination of hydroxychloroquine and the antibiotic azithromycin, as used in one French experiment with altogether only 80 patients, calling it a “game changer.”

Aix-Marseilles University professor Didier Raoult, who led the team, has reported that 93% of patients treated with the cocktail tested negative eight days into treatment. A second trial conducted with hydroxychloroquine was inconclusive.

Raoult, who is controversial in France, especially as a climate change skeptic, said the successful outcome of one of his studies allowed patients to rapidly be discharged from “highly contagious wards” with a mean length of stay of five days. He urged other teams to “urgently evaluate this cost-effective therapeutic strategy.”

France’s health authority has now also allowed emergency use of hydroxychloroquine as a COVID-19 treatment, provided the patients are without other options and the risks are justified. Other countries have indicated may follow suit, barring any catastrophic results that may be reported.

Some of Raoult's peers have suggested his methodology is flawed, and have noted that the doctor failed to mention that one of his patients had died. Ironically, Raoult and several of his co-authors were banned from publishing in any American Society for Microbiology (ASM) journals for a year due to errors in their published studies.

In another hospital in France, treatment with hydroxychloroquine on at least one coronavirus patient was halted on Apr. 8 after it became a "major risk" to the patient’s  cardiac health, press reports said. Trials recently conducted in Sweden also were ended early due to serious side effects.

Critics of the virus treatment with hydroxychloroquine, which was invented by Bayer in 1934, have said there is not enough evidence that either of the two drugs used in France is able to reduce viral load and prevent the inflammatory response that can destroy the lungs of seriously ill coronavirus patients – those for which it is to be reserved

Some said they worry about serious side effects, in particular cardiac arrhythmia, which can lead to heart attacks in patients with a history of heart disease or those on antidepressants. Other side effects have been described as vision loss or psychosis.

Bending drug approval rules?

Other critics say that with the rush to find effective treatments in the absence of a vaccine, the US government in particular is bending its own rules for drug approval, and the price surge is upending pharmaceutical pricing.

The president’s efforts to find a miracle cure reveal how this could change the nature of drug oversight, a field long governed by strict rules of science and testing, a Reuters report concludes. “Rarely, if ever,” it says, “has a president lobbied regulators and health officials to focus their efforts on specific unproven drugs.”

Reuters points to guidance published by the federal government-run US Centers for Disease Control and Prevention (CDC) telling doctors they had the option to prescribe the drugs, with key dosing information based on unattributed anecdotes – “something that is never done.”

“The president is short-circuiting the process with his gut feelings,” Jeffrey Flier, a former dean of Harvard Medical School, told Reuters. “We are in an emergency and we need to rely on our government to ensure that all these potential therapies are tested in the most effective and objective way.”

Right wing personalities also hype the drug

US media have focused heavily on the motivation behind Trump’s glowing recommendation of a treatment he with his non-medical background knows nothing about for a disease he knows nothing about. Some have speculated that he has a financial stake in one of the drugmakers, while others have surmised that the president is grasping at straws to find a ticket to re-election in November.

Research by the New York Times revealed several connections between Trump and his confidants related to hydroxychloroquine. Through Fisher Asset Management, a brokerage run by a major donor to Republicans, the president (also a beneficiary) has a small financial interest in Sanofi, which sells the drug outside the US, but it is thought not big enough to make much of an impact on his bottom line if the drug became a successful treatment.

Invesco, the fund previously run by Wilbur Ross, current US Secretary of Commerce, owns shares in Mylan and Sanofi.

Financial considerations aside, Washington political columnist Philipp Bump has noted that the most vocal cheerleaders of hydroxychloroquine are right wing media-savvy personalities such as Fox News host Laura Ingraham, Oracle founder Larry Ellison, TV doctor Mehmet Oz and Trump’s personal lawyer Rudi Giuliani.

The latter has connections to Vladimir Zelenko, a Ukrainian doctor who has enjoyed popularity with conservative outlets for claims he has successfully treated patients with a drug cocktail of hydroxychloroquine, azithromycin and zinc sulfate.