With an ongoing phase II trial showing that a pair of its SARS-CoV-2 neutralizing antibodies has so far reduced viral load, symptoms and COVID-19-related hospitalization and ER visits, Eli Lilly and Co. has asked the FDA to consider an emergency use authorization (EUA) for one of the components, LY-CoV555. A separate EUA for the combination could follow in November.
Also known as bamlanivimab, the candidate is one of the first products of the company's ongoing collaboration with Abcellera Biologics Inc., first announced in May.
The initial EUA request for LY-CoV555 monotherapy covers higher-risk patients who have been recently diagnosed with mild to moderate COVID-19. Should it be approved, Lilly's team anticipates being able to supply as many as 1 million doses of the monotherapy before the end of the year, CEO David Ricks said. The supply of combination therapy could increase substantially beginning in the first quarter of 2021, as additional manufacturing resources come online throughout the year, including Lilly's recently announced manufacturing collaboration with Amgen Inc., he added.
How soon approval of the EUAs might happen and what the medicines could eventually cost patients was less clear. On the topic of availability of the monotherapy, Lilly's chief scientific officer, Dan Skovronsky, said that an "adequate and deep scientific review inevitably takes time, right? We've submitted a lot of data to the agency, and our expectation is that there will be a careful and thorough review" there.
Addressing potential pricing, Ricks was similarly vague, repeatedly asserting the company's desire to "make sure that patients have no or very, very low out-of-pocket costs anywhere in the world."
"We don't want to allocate this product based on ability to pay or even to the highest bidder. Rather, we're going to predefine tiers based on GDP per capita or metrics like that and really ask wealthy nations to pay more than poor countries," Ricks said.
In the end, "whatever we end up charging, it should create value for society beyond Lilly," he added.
In addition to the EUA request made for LY-CoV555 monotherapy, the company said it is expecting to request another EUA for the combination of that candidate with its other SARS-CoV-2 neutralizing antibody asset, LY-CoV016, in November, once additional safety data on the combination are available and sufficient supply has been manufactured, Ricks said.
"While we are excited with the progress, the recent news in Europe and U.S. reinforces that the COVID-19 pandemic remains a significant global health concern and underscores the need for treatments and vaccines to combat this virus," he told listeners on a company conference call held Oct. 7.
In addition to updates on the EUAs, Lilly offered new data from its Blaze-1 study, a randomized, double-blind, placebo-controlled phase II trial designed to assess the efficacy and safety of LY-CoV555 and LY-CoV016, developed in collaboration with Shanghai Junshi Biosciences Co. Ltd., for the treatment of symptomatic mild or moderate cases of COVID-19 in the outpatient setting.
While the ongoing study has three parts, Wednesday’s update focused on part A, an evaluation of three different doses of LY-CoV555 vs. placebo, and part B, which looked at the antibody combo vs. placebo. Placebo patients were shared across all therapy arms in the completed cohorts.
The primary outcome measure for the completed arms of the trial was change from baseline to day 11 in SARS-CoV-2 viral load.
Over the course of 11 days, investigators saw about 99.99% clearance of virus in the placebo group. But both monotherapy and combination therapy with Lilly's antibodies showed a more rapid decrease in viral load.
"But we didn't fully understand the meaningfulness of viral load and changes in viral load over time because this was the first study of its kind that measured serial viral load in [nasopharyngeal swab] of patients in an ambulatory setting,” Skovronsky said.
While the trial was designed primarily as a safety and biomarker study, "we did see very meaningful clinical efficacy signals," he said.
Evercore ISI analyst Umer Raffat called the viral load impact "a big deal" that will get attention since "remdesivir was unable to show a benefit on viral load."
"The fact that neutralizing antibodies have a clear antiviral effect bodes well for vaccines... however, keep in mind that antibody titers on vaccines do fade in a few months... and establishing the effect of T cell vs. nab titers on protection is the single biggest question that will be pending post the initial round of vaccine phase III data in November," he said.
Both monotherapy and combination therapy were generally well-tolerated in the trial, with no clinically meaningful differences in treatment-emergent adverse events across the treatment groups, the company said.
Lilly's shares (NYSE:LLY) rose 3.4% to $148.96 on Wednesday.
An upgrade for hydroxychloroquine?
Separately on Oct. 7, Taiwan Liposome Co. Ltd. (TLC) said it has received regulatory blessings to start a phase I trial of TLC-19, the company's liposomal suspension of hydroxychloroquine (HCQ) for inhalation in 30 healthy volunteers. Data from the trial will serve as a basis for subsequent trials in patients with COVID-19. TLC's U.S.-listed shares (NASDAQ:TLC) were up 36% to close Oct. 7 at $5.94 following the news.
The company said that "orally administered HCQ cannot reach therapeutic levels due to its dose-limiting toxicities" and clinical results around the world have called into question how beneficial the drug can really be for COVID-19 patients, notably leading the FDA to revoke its EUA for the medicine earlier this year. But using about 1% of the highest oral dose of the drug tested, TLC said, TLC-19 delivers the drug directly to the airways and lungs, potentially avoiding systemic toxicities associated with oral HCQ while providing a sustained effective concentration at the primary site of infection.
The company, which has operations in both South San Francisco and Taipei, has already received approval from both Australian and Taiwanese regulators to initiate its study, it said.