Since more than 40% of U.S. coronavirus deaths have links to U.S. long-term care facilities, Eli Lilly and Co. is getting on the road with a clinical trial design that takes researchers directly to outbreaks.
The company plans to enroll as many as 2,400 residents and staff in its phase III study of LY-CoV555 for preventing COVID-19 by showing up with custom retrofitted recreational vehicles for supporting mobile labs and clinical trial material prep at facilities experiencing outbreaks.
Lilly will also deliver all supplies in the first-of-its-kind COVID-19 clinical trial to create an on-site infusion clinic and supply the staff to assist. The facilities Lilly will travel to include skilled nursing and assisted living facilities with recently diagnosed COVID-19 cases.
Facility residents and staff will receive a single dose of LY-CoV555 in an effort to determine if it reduces the SARS-CoV-2 infection rate through four weeks and a COVID-19 complication rate through eight weeks.
LY-CoV555 is a neutralizing IgG1 monoclonal antibody directed against the spike protein of SARS-CoV-2 and is the lead antibody from Lilly’s collaboration with Abcellera Biologics Inc., of Vancouver, British Columbia. The antibody was found by Abcellera in a blood sample taken from one of the first recovered U.S. COVID-19 patients.
Daniel M. Skovronsky, Lilly’s chief scientific officer and president of Lilly Research Labs, said on the company’s July 30 earnings call that the timing of data disclosures depends on how fast the trials enroll and what the data show. He added that Lilly and others have looked at monotherapy vs. combination therapies and found combinations don't offer an efficacy boost.
“A single antibody can generally neutralize the virus just as well as combinations of antibody,” Skovronsky said. “The reason that people sometimes try combinations of antibody is because they're worried that over time, resistance could emerge. So I don't expect to see any efficacy boost or efficacy diminution from having a combo or monotherapy in clinical trials. What we'll be looking for instead is whether or not there's emergence of resistance.”
Mizuho Securities analysts wrote Monday that they expect data from the LY-Cov555 antibody study later this year.
In June, Lilly dosed its first patients in a phase I test of LY-CoV555. Under the deal with Abcellera, the two companies will equally share initial development costs toward a product, after which Lilly will be responsible for all further development, manufacturing and distribution work and costs.
Mizuho Securities analysts noted Monday that Lilly delivered an “admittedly messy” second-quarter 2020 earnings report that was negatively impacted by the COVID-19 pandemic and said they were surprised to see the stock down more than 7% in the two trading days since the numbers were announced.
The traveling, on-site clinical trial is being conducted with the NIH, the COVID-19 Prevention Network and several long-term care facility networks.
Lilly's work joins significant efforts underway at Regeneron Pharmaceuticals Inc., Roche Holding AG, Vir Biotechnology Inc., Celltrion Inc. and academic institutions such as the University of Toronto, all of which are pursuing the development of antibody therapeutics for the virus.
The COVID R&D Alliance, comprising Abbvie Inc., Amgen Inc. and Takeda Pharmaceutical Co. Ltd., has enrolled its first patients in the I-Spy COVID trial for evaluating inflammatory response. The study is testing the efficacy of cenicriviroc, a chemokine (CCR2 and CCR5) dual-receptor antagonist, Otezla (apremilast), a PDE4 inhibitor, and Firazyr (icatibant injection), a bradykinin B2 receptor antagonist, in severely ill, hospitalized COVID-19 patients requiring at least 6L of high-flow oxygen either by mask or nasal cannula, known as level 5 on the World Health Organization COVID scale, an eight-point ordinal scale of clinical severity status.
The primary endpoint is time to achieve level 4 (or less) for at least 48 hours. Key secondary endpoints include ventilator duration time and mortality.
COVID R&D Alliance members share clinical data and crowdsource early stage candidates to identify mechanisms of action and treatments, especially late-stage investigational medicines for severely ill patients. The group uses adaptive platform methodologies for testing multiple therapies simultaneously. The I-Spy COVID trial is sponsored and managed by Quantum Leap Healthcare Collaborative.
CCR2 and CCR5 chemokine receptors have a tie-in with nonalcoholic steatohepatitis’ (NASH) inflammatory and fibrogenic pathways, which are also linked to COVID-19 respiratory sequelae.
Cenicriviroc is currently in a phase III study for treating NASH and has fast track status in adults with liver fibrosis due to NASH.
Otezla is an oral, small molecule used for treating inflammatory diseases that include psoriasis and psoriatic arthritis.
Firazyr is for treating acute attacks of hereditary angioedema in adults 18 and older.
SVB Leerink’s Geoffrey Porges wrote Monday that Abbvie management indicated that the company’s business had recovered to 90% of pre-COVID-19 levels in July.
“Abbvie remained as the most resilient company among large-cap biopharma companies, and its 90-95% recovery was meaningfully higher than that of its peers (many in the 60% recovery range),” Porges wrote. “Despite the ongoing pandemic around the country, we expect Abbvie to perform better and continue to exceed investors’ expectations in the second half.”