AbbVie’s Kaletra doesn’t work in COVID-19, say Chinese scientists

A clinical trial of AbbVie’s HIV therapy Kaletra conducted by researchers in China has undermined hopes it could swiftly be repurposed to fight the coronavirus epidemic.

The study, just published in the New England Journal of Medicine, found little benefit when Kaletra (lopinavir/ritonavir) was added to standard care such as ventilator support in patients who were hospitalised with COVID-19 infections that was severely affecting their lung function.

Kaletra was trialled on the strength of lab tests which suggested it might inhibit coronaviruses, including SARS and MERS-COV which caused outbreaks a few years ago and have some similarities to the COVID-19 virus.

The team compared standard care alone to standard care plus Kaletra over 14 days in 199 patients, and found there was no effect from the drug on the time to clinical improvement, defined as either a two-point improvement on a seven-point symptom scale or discharge from hospital, whichever came first.

There were fewer deaths in the drug-treated group, but the difference wasn’t big enough to reach statistical significance. Mortality was high in the trial, at around 22%, suggesting the patients were very sick on enrolment.

There were also trends in favour of the Kaletra group on the length of stay in intensive care and the time to discharge from hospital, according to the researchers, led by Bin Cao of the China-Japan Friendship Hospital in Beijing.

That has led to some calls for the drug not to be abandoned prematurely, particularly as there was wide variability among the patients in the time from diagnosis to the start of treatment.

Some scientists and analysts have suggested that earlier treatment, potentially in milder cases of the disease, should be tested, although the Chinese team noted there was no difference in viral load between the two groups, with around 40% of patients in both still testing positive for the virus after two weeks.

That would suggest Kaletra isn’t acting directly against the virus as hoped, write NEJM editors Lindsey Baden and Eric Rubin in an editorial accompanying the research paper, although they note the secondary endpoint results are “intriguing.”

The researchers say there were three deaths among patients in the Kaletra arm before they received drug treatment, and if these were excluded Kaletra just sneaked over the threshold for a significant effect in mortality.

The editorial points out however that “such a change is debatable, since no such removal occurred in the control group.”

It nevertheless describes the efforts of the Chinese team as “heroic” and includes important takeaways for other researchers designing trials to provide quick answers on the efficacy of drugs for emerging diseases.

One important point is that Kaletra is known to have only modest activity against the coronavirus, so there could still be a benefit from the drug if used in combination with other drugs.

That might include Gilead’s remdesivir or chloroquine, also in clinical testing and is included among a basket of drugs that the World Health Organization (WHO) plans to test in a large-scale trial unveiled this week called SOLIDARITY.

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