Humanigen Inc. reported progress in COVID-19 treatment by deploying a drug candidate, lenzilumab, that was created to fight cytokine storms in CAR T patients. The drug is partnered for the latter with Gilead Sciences Inc., which rolled out pandemic news of its own related to the investigational broad-spectrum antiviral Veklury (remdesivir).
Burlingame, Calif.-based Humanigen unveiled findings that lenzilumab, which targets human granulocyte macrophage-colony stimulating factor (GM-CSF), helped an elderly Caucasian male patient whose history included an array of conditions: type 2 diabetes, coronary artery disease with a coronary artery bypass graft, systolic heart failure, severe chronic obstructive pulmonary disease (COPD) with emphysema and obstructive sleep apnea. The patient, 77, tested positive for SARS-CoV-2 and was admitted to an intensive care unit in March, where he was put on respiratory isolation.
Doctors treated him with steroids, antibiotics for community-acquired pneumonia, and bronchodilators for possible COPD exacerbation, along with hydroxychloroquine plus zinc. Still, he deteriorated for the next 12 weeks, with an increase in oxygen demand from continuous low-flow to high-flow, and eventually intermittent bilevel positive airway pressure. During that time, he developed acute respiratory distress syndrome.
At week 13 of hospitalization and after unsuccessful attempts at oxygen weaning, an emergency, single-use IND for lenzilumab was cleared by the FDA and administered to the patient. Seven days later, his oxygen need decreased from high-flow to low-flow nasal cannula, and he was able to walk outside of his hospital room with physical therapy. Sixteen days after treatment, he was discharged from the hospital on home oxygen.
A separate case-control study with lenzilumab in severe and critical COVID-19, published in Mayo Clinic Proceedings, turned up an 80% reduction in relative risk of invasive mechanical ventilation and/or death for patients treated with lenzilumab compared to the matched control group. The drug is being evaluated in a phase III trial for COVID-19 pneumonia, with results due late in the fourth quarter of this year. The U.S. NIH is sponsoring a second experiment that should yield data early next year. GM-CSF is known to mediate the hyper-revved immune response that equals a cytokine storm,
Humanigen “should not be thought of as a ‘COVID company,’” Roth analyst Tony Butler wrote in a late September report. “But, in fact, there is evidence in the scientific literature that [lenzilumab] may slow or impede the progression of COVID pneumonia.” He cited results from the small Mayo cohort showing such patients get out of the hospital much quicker when treated with lenzilumab than others. Referring to a 1971 song by The Doors, Butler called Humanigen a “rider on the [cytokine] storm,” with COVID-19 portraying “the hitchhiker wandering aimlessly from town to town, the killer on the road. We all wonder when and exactly how we strangle SARS-CoV-2.”
Humanigen also said its type B meeting with the FDA included feedback on emergency use authorization (EUA) submission plans. Officials said the company’s intended package may be sufficient to support an EUA request, subject to phase III data. Regarding chemistry, manufacturing and controls, EUA labeling, and the statistical analysis outline, the FDA said no material changes are needed. The phase III bid has been expanded to Brazil, with seven sites actively enrolling. Patients already have been dosed at 17 sites in the U.S., including California, Texas and Florida. The company has gained the go-ahead from Mexico’s regulatory body to expand the study in that country, too, which bears the fourth-highest reported deaths worldwide.
With Foster City, Calif.-based Gilead, lenzilumab is undergoing phase I/II inquiry for patients with relapsed or refractory large B-cell lymphoma (LBCL). Called Zuma-19, the trial is testing lenzilumab when combined with Yescarta (axicabtagene ciloleucel), Gilead’s autologous anti-CD19 CAR T-cell therapy. Yescarta was approved by the FDA in October 2017 as the second gene therapy given the agency’s blessing for certain types of non-Hodgkin lymphoma: relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma; and DLBCL arising from follicular lymphoma. Yescarta did not take off as Gilead might have hoped after acquiring its developer, Kite Pharma Inc., for $11.9 billion, and chalked $456 million in sales last year.
Separately, Gilead said scale-up of its COVID-19 treatment, Veklury, has gone well. The company is now meeting real-time demand in the U.S. and expects to do the same globally this month, even if the virus surges. Gilead said it has donated 1.5 million vials of Veklury, which works by inhibiting RNA-dependent RNA polymerase, and provided clinical drug supply at no cost for evaluation in trials around the world. The firm will be responsible for distributing Veklury in the U.S., now that the previous distribution agreement with the U.S. federal government has ended. To ensure stable management of drug supply, the company said, Chesterbook, Pa.-based Amerisourcebergen Corp. will continue as the sole U.S. distributor through the end of this year, and will sell the product directly to hospitals. As an investment story, Gilead “remains tough for investors, though fundamentally [the company is] much better off than last year,” in the opinion of Jefferies analyst Michael Yee. The “rise-and-fall sentiment” regarding Veklury “was a distraction for half the year (though it brought in unanticipated cash flow),” he wrote in an Oct. 2 report.