Both ballyhooed and questioned as a potential savior from COVID-19, hydroxychloroquine is about to get a high-profile test by Basel, Switzerland-based Novartis AG. The company has reached an agreement with the FDA to run a phase III trial evaluating the drug for the treatment of hospitalized patients with COVID-19, with enrollment of 400 patients beginning within weeks and results to be reported as soon as possible. The study will join a multitude of others, some of ever larger scale, that are testing the drug against the pandemic infection.
“We recognize the importance of answering the scientific question of whether hydroxychloroquine will be beneficial for patients with COVID-19 disease,” said John Tsai, head of global drug development and chief medical officer at Novartis.
Novartis said it will conduct the trial at more than a dozen U.S. sites. Furthermore, to "achieve broad access to hydroxychloroquine as quickly as possible in these extraordinary circumstances," the company has pledged to make any intellectual property within its control that relates to the use of hydroxychloroquine to treat or prevent COVID-19 available as needed.
The company also plans to sponsor or co-sponsor clinical trials to study Jakafi (ruxolitinib) and Ilaris (canakinumab) for hospitalized patients with COVID-19 infections. Requests for investigator-initiated trials have been granted for COVID-19-related clinical studies of Jakafi, Ilaris, Gleevec (imatinib), Cosentyx (secukinumab), hydroxychloroquine and valsartan.
Patients in the double-blinded study will be randomized into three groups, with the first group receiving hydroxychloroquine, the second getting hydroxychloroquine plus azithromycin and a third receiving a placebo. Patients in all treatment groups are receiving standard of care for COVID-19.
"Researchers at the company compressed months of work into a few weeks to design the large clinical trial," Novartis said.
Novartis, through its generics and biosimilars division Sandoz, has pledged to donate up to 130 million tablets of hydroxychloroquine to supply global clinical research efforts in the event the medicine is proven beneficial for treatment of COVID-19. Sandoz has already donated 30 million tablets to HHS and is dispatching further shipments beyond the U.S. based on requests from global governments.
Hydroxychloroquine and chloroquine have long been used to treat rheumatology and malaria conditions, respectively. But attention has flowed to the drug since small studies in China and France – where it was tested with azithromycin – have suggested possible benefit of the drug against COVID-19. Results of that early work that were amplified by President Donald Trump during recent White House coronavirus task force briefings.
Despite enthusiasm for the drug in some quarters, others including the American Heart Association, have expressed concern that chloroquine, hydroxychloroquine and azithromycin all prolong QT interval, raising concerns about the risk of arrhythmic death from individual or concurrent use of the medications.
Further trials underway
According to Cortellis, about 155 clinical trials are underway globally to test hydroxychloroquine against COVID-19, either alone or as one medicine among several being tested in multi-arm studies testing competing therapies.
Large studies of chloroquine or hydroxychloroquine underway have been organized by the World Health Organization, private entities and academic centers across the globe. WHO's big studies, Solidarity and its European counterpart Discovery, are slated to enroll thousands of patients who will be treated with remdesivir, Kaletra with or without IFN-beta, or hydroxychloroquine. Both are adaptive trials, meaning that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts.
The U.K.-based Recovery trial, being conducted by researchers at the University of Oxford, is also testing hydroxychloroquine vs. standard of care alone, alongside Kaletra (lopinavir + ritonavir, Abbvie Inc.), azithromycin and low-dose corticosteroids. On April 20, physician and trialist Martin Landray said via Twitter that the study had enrolled 6,000 patients across 170 active sites.
Researchers from Intermountain Healthcare and University of Utah Health in Salt Lake City have launched two trials to test the effectiveness and safety of hydroxychloroquine and azithromycin to treat patients with COVID-19. They plan to enroll nearly 2,300 patients who have tested positive for the virus.
A separate study led by the University of Washington Medical Center in Seattle in collaboration with NYU Langone is testing whether hydroxychloroquine can help prevent COVID-19. It's enrolling 2,000 adult volunteers at six sites. "If everything goes as planned, the eight-week trial could provide answers by summer on whether a preventive dose of the drug is safe and effective," NYU Langone Health said.
While those larger trials proceed, it's likely that additional interim peeks at data on hydroxychloroquine's use as a treatment for COVID-19 will continue to emerge. On Monday, New York Governor Andrew Cuomo said about 20 hospitals in his state would send the first tranche of results of a study on hydroxychloroquine to FDA and CDC.