Shares of Humanigen Inc. (NASDAQ:HGEN) leapt 54.5% to $21.61 March 29 on news that its monoclonal antibody, lenzilumab, improved the relative likelihood of survival without mechanical ventilation in hospitalized patients with COVID-19, setting the company up to submit an application for emergency use authorization (EUA) in the U.S. "as soon as possible," it said. Separately, a combination of two monoclonal antibodies, the Eli Lilly and Co.-Abcellera Biologics Inc.-developed therapy bamlanivimab and the Vir Biotechnology Inc.-Glaxosmithkline plc candidate VIR-7831, demonstrated a 70% relative reduction in persistently high SARS-CoV-2 viral load at day seven compared to placebo for low-risk adult patients with mild to moderate COVID-19, the companies reported.
News of the developments appeared especially relevant on a day that CDC Director Rochelle Walensky expressed a "feeling of impending doom" over the trajectory of the pandemic in the U.S., which appears to be following in the footsteps of countries like Germany, Italy and France, all of which have "experienced a consistent and worrying spike" in COVID-19 cases, she said.
Humanigen's trial was a randomized, double-blind, placebo-controlled study designed to assess whether the use of lenzilumab in addition to current standard of care (SOC) could alleviate immune-mediated cytokine release syndrome and improve ventilator-free survival in hospitalized patients with severe or critical COVID-19 pneumonia. "The mortality rate for hospitalized COVID-19 patients remains unacceptably high, particularly in patients who progress to invasive mechanical ventilation," the company said in a description of the 520-participant study.
Patients in the study were randomized in a 1-to-1 ratio to receive either lenzilumab plus SOC, Veklury (remdesivir, Gilead Sciences Inc.) and/or dexamethasone, per institutional treatment guidelines or placebo plus SOC. Humanigen said Monday that the top-line Kaplan-Meier estimate for invasive mechanical ventilation (IMV) and/or death was 15.6% (95%CI: 11.5-21) in the lenzilumab arm vs. 22.1% (95%CI: 17.4-27.9) in the placebo arm.
About 88% of patients received dexamethasone (or other steroids), 62% received Veklury and 57% received both, balanced across both arms of the study, Humanigen said.
Making the most of the news, Humanigen announced Monday afternoon that it had commenced an underwritten public offering of 5 million shares of its common stock, plus an option for underwriters of the offering to buy up to an additional 750,000 shares. The Burlingame, Calif.-based company intends to use net proceeds from the offering for manufacturing and commercial preparation in the event of receipt of an EUA for lenzilumab. Jefferies, Credit Suisse and Cantor are acting as joint book-running managers for the offering.
Not everyone was convinced there was cause for such big excitement around the shares Monday. "Despite supporting clinical benefit over standard of care, the data are limited in their differentiation from other biologic immuno-suppressive regimes available for off-label use in the indication (namely tocilizumab, per NIH guidelines)," said J.P. Morgan analyst Eric Joseph.
"Accordingly, while EUA/approval path forward for lenzilumab is fundamentally de-risked, we see valuation being offset by a moderated commercial outlook for the product, both in terms of market uptake and pricing potential," he said.
Lilly-Vir combo lowers viral load
A combination of Lilly's bamlanivimab and the Vir-GSK candidate VIR-7831 (GSK-4182136) also made headlines Monday as the partners announced top-line data from the expanded phase II Blaze-4 trial studying low-risk adult patients with mild to moderate COVID-19. Results from the study showed that a 700-mg dose of bamlanivimab co-administered with 500 mg of VIR-7831 demonstrated a 70% (p<0.001) relative risk reduction in persistently high viral load at day seven vs. placebo, meeting the study's primary endpoint.
In addition, the combination therapy demonstrated a statistically significant reduction compared to placebo in the key virologic secondary endpoints of mean change from baseline to days three, five and seven in SARS-CoV-2 viral load, Lilly said. No serious adverse events tied to the combo were seen in the trial.
"Though the secondary endpoint of COVID-19-related hospitalizations or death was not hit, this was due to the fact there were no hospitalizations or deaths in the trial which recruited low-risk adults," said Cowen analyst Phil Nadeau. "Nonetheless, reduction in persistently high viral load has been previously shown to be strongly correlated with clinical outcomes of COVID-19-related hospitalizations and deaths in high-risk patients, so demonstrates potency itself," he said.
Bamlanivimab, formerly known as LY-CoV555, has already been validated – though not approved – for use in the U.S. with two EUAs, first in November 2020 as a monotherapy for treating mild to moderate disease in high-risk patients and again in February as part of a different cocktail for treating mild to moderate COVID-19 cases with etesevimab, a monoclonal antibody Lilly licensed from Junshi Biosciences Co. Ltd.
An EUA application for VIR-7831 on its own has been submitted to the FDA, based on the results of another study, the COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early) trial, which stopped enrollment early based on data from an interim analysis demonstrating an 85% reduction in hospitalization or death vs. placebo, the primary endpoint of the trial.
Meanwhile, Lilly, Vir and GSK said their teams "anticipate engaging with global regulators, including the FDA, regarding the possible co-administration of bamlanivimab and VIR-7831 for the treatment of COVID-19."
Vir’s shares (NASDAQ:VIR) fell 6.1% to $48.38 on March 29. Lilly’s shares (NYSE:LLY) rose 0.6% to $186.34
In all, according to BioWorld stats, there are 690 COVID-19 therapeutics currently in development.