As TrialSite has reported, Lilly’s Bamlanivimab (or LY-CoV555), despite its hi-tech nature as a monoclonal antibody therapy for COVID-19 with an EUA, has its share of challenges. We have outlined how the extreme difficulties in delivering this medicine have led to purchased doses “sitting on the shelf.” Lilly was paid upfront for 300,000 doses at $1,250 a dose, or $375 million in tax dollars with options to buy another 650,000 vials at the same price point by June 30, 2021. Problems with this drug have included supply limits and an infusion requirement that creates complexities in delivery and collateral dangers to infusion centers. On December 23, another publication reminded of an unfortunate update, “Lilly’s monoclonal antibody fails in NIH-sponsored ACTIV-3 trial.” NIH announced preliminary results from a phase 3 trial of Lilly’s antibody, “failed to provide clinical benefit in hospitalized Covid-19 patients.” The therapy product was discovered by AbCellera Biologics and the NIAID, and Lilly is handing development and manufacturing together with AbCellera.
Candidate Did not Expedite Clinical Improvement but Public Monies Keep Flowing
In October the phase 3 trial stopped enrollment after a Data Safety and Monitoring Board recommendation. The Lilly trial is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program, and it “is sponsored by NIH unit NIAID.” As TrialSite has chronicled, ACTIV continues to favor certain investments over others with guidance directing $13+ billion allocation of taxpayer money into just a handful of vaccine and monoclonal antibody developments. Lilly, along with Regeneron and AstraZeneca represent the top three ACTIV-funded monoclonal antibody prospects. However with Lilly’s failure ACTIV continue to direct huge sums of public taxpayer capital into experimental monoclonal antibody products. Just in Oct. the NIH Foundation-sponsored organization directed $486 million into AstraZeneca’s experimental product and most recently, post Lilly’s failure, directed funds into GlaxoSmithKline/Vir Biotechnology and Brii Biosciences, reported FierceBiotech.
The Phase 3 Lilly trial was both randomized and placebo-controlled under a “master protocol.” Subjects got either LY-CoV555 or a placebo along with standard of care including remdesivir. This sub-study enrolled 326 folks and about 314 randomly were assigned to treatment or placebo. After five days, “50% of those received LY-CoV555 and 54% of placebo recipients were in one of the two most favorable outcome categories.” The scientists concluded that the treatment did not “expedite clinical improvement versus a placebo” at day five. There was no difference in either time to hospital discharge or sustained recovery in the treatment group. FDA granted an EUA for LY-CoV555 in November for non-hospitalized patients.
Authors: “Low Likelihood” LY-CoV555 Improves Outcomes
MedPage recently also reported on this phase 3 study with further details. Study lead Dr. Jens Lundgren of the University of Copenhagen and colleagues also found no significant differences in sustained recovery over a 90-day period. Also, no significant differences in primary safety outcomes. Adverse outcomes occurred in 19% of the investigational arm and 14% in the placebo arm, equating to some concern about safety.
The trial had been paused in October, “due to potential safety concerns in this population.” Study participants ranged over 31 sites in the US, Denmark, and Singapore. 163 patients got the bamlanivimab and 151 got an “infusion of placebo.” Patient median age was 61, and 44% were woman, 21% were Black, and 24% were Hispanic. Around half had a BMI over 30, and 68% had co-morbidities. Despite the 90-day goal, “an interim futility assessment was performed based on a seven-category ordinal scale for pulmonary function, which showed no significant difference between the bamlanivimab and placebo groups.” 14 deaths were reported, nine in the treatment group and five in the placebo group. “These results indicate a low likelihood that LY-CoV555 improves outcomes among hospitalized patients with COVID-19,” the authors noted in their findings reported in the NEJM.