- Novartis will soon start a clinical study designed to deliver definitive proof as to whether hydroxychloroquine, a decades-old malaria pill, can benefit patients with COVID-19.
- The trial, which will enroll about 450 patients, joins a host of other studies that are putting to the test early enthusiasm for the drug's potential. Initial data on hydroxychloroquine's effectiveness has conflicted, setting the drug's proponents — most prominently President Donald Trump — against health officials and experts who've urged for further study.
- Patients enrolled into the Novartis-sponsored study will be randomized to one of three groups, receiving either placebo, hydroxychloroquine or a combination of hydroxychloroquine with the commonly used antibiotic azithromycin.
In mid-March, a group of physicians in the south of France reported early results from a small study of COVID-19 patients treated with hydroxychloroquine and azithromycin.
The data, which were published online without peer review, showed what appeared to be striking reductions of the viral levels in patients' bodies. Soon after, President Trump touted the drug's potential, describing at a press briefing on March 19 "very, very encouraging early results."
The Marseilles trial, however, had many flaws, chief among them its small size and lack of a randomized control group. While the researchers have since updated their findings with data from additional patients, other preliminary studies have shown more mixed results or highlighted the potential harms of using hydroxychloroquine or its various chemical cousins. Clinical tests of the drugs to date have been small and have typically lacked measures, such as randomization or blinding, that are designed to eliminate bias and reduce the chance of misleading results.
Despite contradictory data, the Food and Drug Administration on March 30 granted emergency authorization to two forms of chloroquine, citing in its decision "limited in vitro and anecdotal clinical data in case series." The authorization is not an approval, but does allow distribution of the drug from federal stockpiles to states.
The debate over hydroxychloroquine is the most notable example of how the urgent need for COVID-19 treatments has pressured the drug development process, which is designed to move in phases and answer one specific question at a time. Research efforts to date have been fragmented and chaotic, resulting in a muddle of data that make drawing definitive conclusions difficult.
A number of studies, Novartis' planned trial now among them, aim to more rigorously test early hypotheses about which existing drugs might help. Several large ones examining hydroxychloroquine are already underway in the U.S., the U.K. and France.
Large, randomized studies of hydroxychloroquine (HCQ) as a treatment for COVID-19
|Study sponsor||Treatment setting||Target enrollment||Control group?||Details|
|INSERM||Hospitalized adults||3,100||Yes||Tests four treatments, including HCQ, in parallel|
|Columbia Univ.||Post-exposure prophylaxis (PEP)||1,600||Yes||Tests HCQ PEP among household contacts of COVID-19 patients|
|Univ. of Minnesota||Pre-exposure prophylaxis||3,500||Yes||Tests once-weekly and twice-weekly dosing against placebo|
|Univ. of Washington||Post-exposure prophylaxis||2,000||Yes||Tests HCQ sulfate among close contacts of COVID-19 patients|
|Mass General, NIH||Hospitalized adults||510||Yes||Tests HCQ in adults hospitalized with COVID-19|
|Henry Ford Health System||Healthcare workers||3,000||Yes||Tests HCQ in healthcare workers and first responders in Detroit|
|Cambridge Univ. Hospitals, NHS||Healthcare workers||1,000||Yes||Tests HCQ in National Health Service workers|
Novartis said its trial will be conducted at more than a dozen sites in the U.S. and will begin enrolling patients in the coming weeks. Results will be reported as soon as possible, the company said, but data from other studies will likely be available sooner.
"We recognize the importance of answering the scientific question of whether hydroxychloroquine will be beneficial for patients with COVID-19 disease," said John Tsai, Novartis' chief medical officer, in a Monday statement.
Through its generic drug division, Sandoz, Novartis last month pledged to donate up to 130 million doses of hydroxychloroquine by the end of May, provided health authorities authorize its use. Other manufacturers, including Mylan and Teva, have announced similar donations.