- A clinical study of patients in China with severe COVID-19 found little benefit to a generic HIV therapy thrust into testing as a possible treatment for the new coronavirus, dashing hopes the drug could be repurposed to combat the global pandemic.
- Trial results, published Wednesday in the New England Journal of Medicine, showed coronavirus patients given the antiviral drug Kaletra improved no faster than those who received only supportive care, such as supplemental oxygen and ventilator support.
- While Kaletra is approved to treat HIV, previous laboratory tests suggested the drug could be active against the SARS and MERS viruses, which share genetic similarities with SARS-CoV-2, the new coronavirus that's spread across the world. Kaletra is just one of many existing drugs being studied in hopes of hitting on an effective therapy.
On Jan. 18, when the study published Wednesday began, there were fewer than 300 confirmed cases of COVID-19 in China.
Over the next two weeks, as researchers at Jin Yin-Tan Hospital in Wuhan, China enrolled coronavirus patients into the trial, the total cases reported by China had soared to more than 17,000, making clear the severity of the global health threat facing the country and the world.
Conducting a randomized study of severely ill patients, all amidst a fast-moving outbreak, was a monumental task.
"This was a heroic effort," wrote Lindsey Baden and Eric Rubin, both editors at the New England Journal of Medicine, in an associated editorial. "As we saw during the 2014 Ebola outbreak in West Africa, obtaining high-quality clinical trial data to guide the care of patients is extremely difficult in the face of an epidemic, and the feasibility of a randomized design has been called into question."
"Yet Cao's group of determined investigators not only succeeded but ended up enrolling a larger number of patients than originally targeted," they added, referring to the study's lead author, Bin Cao of the China-Japan Friendship Hospital in Beijing, China.
Unfortunately, results did not bear out the researchers' efforts.
After 28 days of study, no benefit was observed among the 99 patients given Kaletra on top of supportive care, compared to the 100 who were treated only with supportive care. Although fewer patients in the Kaletra group died than did those in the standard treatment group, the difference was modest.
Patients were measured on a seven-point scale, with "1" indicating discharge from the hospital and "7" indicating death. The groups were compared on time to clinical improvement, which was defined as either a 2-point improvement or discharge.
Median time to clinical improvement was 16 days in both groups.
The study authors did note, however, that three patients assigned to receive Kaletra died before they could be given the drug. Removing those patients from the statistical comparison — known as a modified intent-to-treat analysis — showed a 1-day benefit to Kaletra versus supportive care.
"Such a change is debatable," the NEJM editors wrote, "since no such removal occurred in the control group."
Other secondary comparisons, such as length of stay in an intensive-care unit or time from randomization to discharge, appeared to show an advantage to Kaletra, and earlier treatment with the drug was associated with better outcomes.
That could be important, according to Umer Raffat of the investment firm Evercore ISI, who argued in a note to clients that the timing of antiviral treatment is critical.
Tests of viral activity didn't show an effect from treatment, however, and 40% of Kaletra-treated patients had detectable coronavirus RNA at the end of the study.
"Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired," the NEJM editors wrote.
Serious side effects were reported more frequently in the standard treatment group than the Kaletra group, but those receiving the drug more often experienced gastrointestinal issues like nausea and vomiting.
Kaletra, a combination of the drugs lopinavir and ritonavir, is now generic. The branded version is made by AbbVie, which last week said it was working with global health authorities to determine its efficacy against SARS-CoV-2, as the new coronavirus is officially known. The company did not return a request for comment from BioPharma Dive by publication.
Scrambling to stem the virus' spread, scientists and doctors have started scores of studies testing existing antiviral drugs like Kaletra or Tamiflu. One, an experimental therapy called remdesivir and developed by Gilead, is considered the most likely to be effective against SARS-CoV-2.
But there was some hope for Kaletra, particularly since it is already available to manufacture at global scale. On Wednesday, the World Health Organization included it and remdesivir in an "umbrella" study also testing the antimalarial drug chloroquine.
The Kaletra results aren't a definitive answer, given its small size and the rushed environemnt in which it was run. Researchers conducted the trial open-label, meaning doctors knew they were giving patients the drug, because there was no time to prepare placebo versions of Kaletra.
But as infections mount in countries outside of China, the urgency to find or develop a treatment has only grown higher.