Malaria drug chloroquine, AbbVie’s HIV combo therapy Kaletra and an influenza med called Arbidol are among top candidates that physicians are repurposing for the treatment of COVID-19. Despite backing from officials, though, the three have disappointed separately in two Chinese clinical trials of mild patients.
Hydroxychloroquine, a more tolerable form of chloroquine, didn’t top placebo at clearing the coronavirus among mild Chinese patients, or helping them reach normal temperature sooner, Evercore ISI analyst Umer Raffat noted in a Tuesday memo.
Separately, neither Kaletra—a combination of HIV antivirals lopinavir and ritonavir—nor Arbidol (umifenovir) delivered benefits in viral clearance or symptom relief compared with no antiviral treatment in a small Chinese study in mild-to-moderate COVID-19 patients, results published Monday on the preprint site medRxiv show.
Chinese health authorities first included Kaletra in their coronavirus treatment guidelines in late January, and chloroquine and Arbidol—which is available in China and Russia, but not in Western countries—were added in an update on Feb. 19. These decisions were backed by some early preclinical evidence in lab dishes or anecdotal success in the clinic amid a lack of approved drugs for the new pathogen. During a press conference on Thursday, President Donald Trump highlighted chloroquine as a promising candidate.
But so far, these three meds have not lived up to their expectations in clinical trials.
First, in a small study involving 30 patients, hydroxychloroquine, used on top of conventional treatments, cleared the virus in 13 (86.7%) cases on day 7, while 14 (93.3%) patients in the control group had the virus cleared, according to a study abstract Raffat obtained. One patient on the malaria med progressed to severe during the treatment.
The median duration from hospitalization to virus-negative testing, as well as the median time to body temperature normalization, were also similar between the two arms. The only positive signal was disease progression shown on CT scans, which five hydroxychloroquine cases showed, versus seven in the control group. But Raffat said the trial size was simply too small to draw conclusions.
The results clearly contradict an article published last week in The Lancet, in which two researchers described the study as showing “positive preliminary outcomes,” he said.
“It really puzzles me why we’re seeing inaccurate characterizations of clinical data,” Raffat wrote. “In my humble opinion, having an honest discussion around emerging clinical data would actually help the progress.” He also complained about a lack of information concerning how long after showing symptoms the patients were dosed, as well as the baseline viral loads across arms. “Parsing through emerging data for these important drivers of success can help define what an effective treatment window and optimal candidate looks like,” he said.
As for the other trial, the median time of positive-to-negative conversion of SARS-CoV-2 was 8.5 days among 21 patients who got Kaletra, 7 days for 16 patients in the Arbidol group, and only 4 days in seven control subjects. Conversion rates at 7 and 14 days “did not show significant differences” among all three groups.
What’s more, the researchers also found no major differences among the groups in terms of the need for fever-lowering meds, cough alleviation, improvement in chest CT scans or the deterioration of clinical status.
For Kaletra, this is not the first trial flop. A group of physicians treating patients at Jin Yin-tan Hospital in Wuhan, China, recently found the HIV combo didn’t offer additional benefits over standard care in severe COVID-19 patients.
That study enrolled 199 patients from Jan. 18 to Feb. 3, the early days of the outbreak. It’s possible that Kaletra couldn’t do its work properly because physicians at that time hadn’t found the best supportive care. The patients entered the study long after showing symptoms and were severely ill with tissue damage.
Raffat at the time noted a positive trend in those who started the treatment earlier, suggesting that the outcomes may be better for those who begin taking the drug when symptoms are less severe. But in a separate note, CLSA analyst Tony Ren argued that “it is the [sicklier] patients who need such therapy.”
Still, these drugs may have other opportunities to prove their worth in the fight against COVID-19. For one, the World Health Organization has unveiled plans for a large-scale global trial, dubbed Solidarity, to test promising antivirals in thousands of patients around the globe. The treatments to be examined include Gilead Sciences’ remdesivir, chloroquine and hydroxychloroquine, Kaletra, and a cocktail of Kaletra plus interferon-beta.