A drug from Shkreli's former company Humanigen shows early promise in COVID-19

Although infection with the novel coronavirus can lead to severe pneumonia, most deaths associated with COVID-19 are caused by a complication called cytokine storm, an immune overreaction marked by the activation and release of large numbers of inflammatory molecules that can damage the lungs.

Among the many drugmakers aiming to address the syndrome to achieve better COVID-19 outcomes is Humanigen, a company briefly run by fallen “Pharma Bro” Martin Shkreli. The company changed its name from KaloBios in 2016 shortly after Shkreli was arrested on securities fraud charges. Now, the company is reporting positive data from a study of its experimental drug lenzilumab in a small group of coronavirus patients who received it on a compassionate-use basis.

Treatment with lenzilumab helped patients with severe and critical COVID-19 pneumonia recover after a median of five days in the 12-patient study, which was conducted by researchers at Mayo Clinic and published on the preprint site medRxiv. That was a lot faster than the 10- and 11-day recovery time with Gilead Sciences’ remdesivir—the only drug with an FDA emergency authorization in COVID-19—as posted in a separate placebo-controlled clinical trial conducted by the National Institutes of Health.

Encouraged by the early results, Humanigen has launched a phase 3 trial of lenzilumab in COVID-19. The study aims to enroll 238 hospitalized patients who are not on invasive ventilation to see whether adding the drug to standard of care can reduce the need for such aggressive support or the incidence of death.

Lenzilumab is an antibody that inhibits GM-CSF, one of the inflammatory cytokines that has been linked to cytokine storm in COVID-19. It’s the lead candidate in Humanigen’s pipeline. The drug is also being tested in clinical trials of CAR-T therapy-related cytokine storm, acute graft-versus-host disease, asthma and other conditions.

In the compassionate use program, which allows patient access to an investigational drug outside a clinical trial, lenzilumab led to rapid clinical improvement. Of the 12 patients who received lenzilumab, 11 were already discharged at the data cutoff date. The treatment also produced a significant improvement in oxygenation and in the reduction of inflammatory cells, according to the researchers.

The results were particularly encouraging because all of the patients in Humanigen's trial had underlying diseases such as diabetes, hypertension, chronic kidney disease or asthma, as well as at least two inflammatory biomarkers indicative of high risk of progression, said Dale Chappell, Humanigen’s acting chief scientific officer, during a conference call Tuesday.

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Five patients in the study did receive other COVID-19-targeting drugs. Two patients got lenzilumab together with hydroxychloroquine, the antimalarial drug for which the FDA recently revoked an emergency authorization due to lack of proven benefits in controlled studies. Two patients who had failed either hydroxychloroquine or remdesivir later improved on lenzilumab. The only patient who remained on invasive ventilation as of the data cutoff date received both steroid therapy and the anti-GM-CSF drug.

To put lenzilumab’s observed clinical improvement and hospital discharge data into context, Humanigen ran a secondary analysis comparing patients with similar baseline characteristics treated with lenzilumab to those who got remdesivir in the NIH ACTT-1 clinical trial.

In those separate studies, lenzilumab’s five-day median recovery speed did outpace remdesivir’s in a similar patient population, according to the company. And lenzilumab achieved that with just one day of treatment, in which it was given three times 8 hours apart. In comparison, remdesivir is administered in regimens of five or 10 days.

Cross-trial comparisons have their limitations, however. Humanigen's analysis involved just 12 coronavirus patients, while remdesivir’s clinical trial included about 1,000 people. What's more, there was no control group in the lenzilumab study. Nevertheless, Chappell argued that it provides early evidence for lenzilumab’s potential and can guide the phase 3 study.

“Given that remdesivir is the only therapeutic currently to have an emergency use authorization from the FDA, it represents the standard of what might be considered approvable by the agency if these results from lenzilumab were replicated in a larger controlled trial,” he said.

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Many other approaches are being tested for dampening the cytokine storm in COVID-19. Chinese biotech I-Mab Biopharma recently reported positive results from a small clinical study of its GM-CSF candidate TJM2. Roche is testing its IL-6 inhibitor Actemra, and AstraZeneca is studying BTK leukemia drug Calquence. Eli Lilly just started a pivotal study of its JAK arthritis med Olumiant, after an artificial intelligence analysis by BenevolentAI flagged it as having both anti-inflammatory and antiviral mechanisms.

Humanigen doesn’t think of remdesivir as a competitor, Chappell explained. Because lenzilumab is an immunomodulator, it could work “potentially synergistically” with the antiviral, he said. In fact, patients in both arms of the phase 3 study are allowed to receive other drugs, including convalescent plasma.