The frantic efforts are being done for the development of a vaccine against COVID-19 amid the deadly pandemic. Experts say that it will take at least 12 to 18 months so companies and doctors are trying to repurpose the already existing drugs in the battle against the novel coronavirus.
The regulatory situation is advancing quickly. In many administrations, doctors can use their discretion for using approved medications off-label for other diseases but their widespread use must be backed up by evidence from clinical trials and the approval of the regulators.
There is some confusion on that front as shown when President Donald Trump proclaimed that the Food and Drug Administration has approved the use of antimalarial chloroquine and hydroxychloroquine for the treatment of COVID-19 patients. The claim was walked back immediately by FDA chief Steven Hahn and the director of the National Institute of Allergy and Infectious Disease, Anthony Fauci.
These drugs are approved by the FDA for the treatment of malaria, rheumatoid arthritis and lupus. FDA has allowed the ‘compassionate use’ of these drugs against novel coronavirus in acute cases.
Hahn emphasized that are no approved treatments for COVID-19 while Fauci stressed the importance of clinical trials to prove efficacy and safety of these drugs.
The clamour around hydroxychloroquine, chloroquine and combinations with other medicines is mostly based on small, preliminary clinical studies and in vitro laboratory tests.
For instance, the French study of 20 Chinese COVID-19 patients gave early evidence in March that the combination of azithromycin and hydroxychloroquine might be effective against SARS-CoV-2. Patients who received the drugs exhibited a reduction in viral titer compared to controls and the duration of their illness was reduced.
However, the situation is far from clear as in another clinical trial involving 30 Chinese patient hydroxychloroquine didn’t appear to be effective. Three US researchers gave a stark warning that ‘anti-viral mechanisms of chloroquine are speculative’. Researchers asserted that caution should be taken during making premature interpretations because trials are still ongoing and interim data have not yet available.
Trials of other antiviral drugs have also been inconclusive. One Chinese study found no significant differences between 44 patients who were receiving either HIVdrugs ritonavir or lopinavir, the Russian antiviral Arbidol or no antiviral drugs as the control.
While another study from China showed that ritonavir and lopinavir didn’t show a faster clinical improvement as compared to patients who only receive standard care.
Adverse side effects need to be considered carefully in search of drugs. An urgent guidance paper by the researchers at the Mayo Clinic at Minnesota, including a genetic cardiologist Michael Ackerman, warns that all these drugs including chloroquine, hydroxychloroquine, ritonavir and lopinavir could cause drug-induced sudden cardiac arrest and death.
These drugs block one of the important potassium channels in the heart that increases the chances of degenerating the heart rhythm of patients and causing cardiac arrest. The same is possible with azithromycin.
Ackerman estimates that almost 1 per cent of patients who tested positive for COVID-19 would be at higher risk of such cardiac events by using these drugs. While no such events have been reported in any of ongoing trials, there have been numerous deaths in the adverse event reporting system of FDA. Ackerman said that the possibility of such drug-induced cardiac arrests and death is not theoretical at all, it will happen if we don’t identify people at highest risk for sudden drug-induced cardiac deaths.
Ackerman calls the current situation of COVID-19 treatment ‘a total Wild West’ and said such kind of tragic results should not be accepted in the battle against SARS-CoV-2.