Operation Warp Speed defends dosing for Lilly mAb, outlines distribution strategy
Warp Speed plans phased rollout for COVID mAbs
Warp Speed plans phased rollout for COVID mAbs
Trump administration officials Tuesday dismissed concerns that FDA may have authorized an ineffective dose of Lilly’s COVID-19 mAb and expressed confidence that bamlanivimab will have a substantial impact on the pandemic if and when healthcare systems come up with safe, effective ways to administer it.
In a briefing for reporters on Tuesday, Operation Warp Speed officials described a plan to allocate bamlanivimab to states and territories based on COVID-19 burden and population-based risk factors. The mAb will be infused initially at hospitals and hospital-affiliated facilities, with administration sites expanded after healthcare systems gain experience with the product.
Over the top
FDA Monday granted emergency use authorization (EUA) to a 700 mg dose of bamlanivimab to treat mild-to-moderate COVID-19 in adult and pediatric patients.
While FDA said the EUA was supported by the BLAZE-1 trial conducted by Eli Lilly and Co. (NYSE:LLY), the agency apparently disregarded the outcomes for the trial’s primary endpoint. The middle, 2,800 mg, dose of bamlanivimab — but not the authorized dose of 700 mg or the high dose of 7,000 mg — met the primary endpoint of demonstrating a statistically significant lowering of baseline viral loads at day 11 vs. placebo.
At the briefing, Janet Woodcock, the leader of Operation Warp Speed’s therapeutics program, said she believes that all the doses tested in the trial exceeded the minimum effective dose. “The trials that have been done in outpatients really do look like we’re well above the top of the exposure-response curve, and therefore the lower dose is a rational choice in this situation because you don’t want to give more of a drug than you need.”
She suggested that a dose below 700 mg could be effective.
“I think you are sort of accepting a dichotomous view of p-values.”
Woodcock, who has temporarily stepped away from her position as director of FDA’s Center for Drug Evaluation and Research to run Warp Speed’s therapeutics program, counseled against focusing on the p-value in the BLAZE-1 trial.
Responding to a question about the lack of significance for the lower dose, Woodcock said, “I think you are sort of accepting a dichotomous view of p-values. If you look at the virology data, there was almost no difference in virus clearance amongst the different doses. Most people can clear the virus on their own and giving them additional antibody isn't doing very much because they are going to make their own antibody and clear the virus.”
She added that for individuals who didn’t clear the virus on their own, each of the tested doses of bamlanivimab “reduced the virus very rapidly” compared with the control group.
Woodcock also pointed to secondary endpoints, particularly a reduction in hospitalizations and medically attended visits, which she noted were lower in each of the bamlanivimab dosing arms than in the control arm.
Woodcock and HHS Secretary Alex Azar said bamlanivimab will keep COVID-19 patients out of the hospital and in the long-run is likely to reduce mortality.
“The goal during this EUA,” Woodcock said, “should be to treat high-risk individuals as soon as possible after they have symptoms and are diagnosed. The data we have suggests that early treatment may help people avoid disease progression and avoid hospitalization.”
Getting into veins
Through Operation Warp Speed, the U.S. government has contracted to purchase 300,000 doses of bamlanivimab this year and has an option to purchase an additional 650,000 doses through June 2021.
Lilly will be able to ship over 80,000 doses this week, Azar said.
The company has had quality control problems at the Branchburg, N.J., plant where bamlanivimab is manufactured. The EUA requires that Lilly hire an independent third party to monitor manufacturing quality, review and sign off on release of each batch, as well as keep FDA informed of discrepancies affecting critical quality attributes and of Lilly’s corrective actions.
As she noted in an interview with BioCentury in October, Woodcock said Tuesday that it will be challenging for healthcare systems to gear up to administer mAbs to symptomatic COVID-19 patients who are at risk of hospitalization.
One of the problems, she said, will be identifying and setting up alternatives to infusion centers that are used to administer medicines to patients with cancer and autoimmune diseases who would be at high risk if they were infected with SARS-CoV2.
Operation Warp Speed is planning a two-phase distribution strategy.
In the first phase, bamlanivimab will be distributed only to hospitals and hospital-affiliated facilities such as emergency rooms and urgent care centers.
CMS has authorized payment for hospitals to administer COVID-19 mAbs in non-traditional locations such as tents set up in parking lots or trailers.
The timing of the start of the second phase, in which distribution will be broadened, depends on how well and how quickly hospitals manage the first phase, Woodcock said. “For the next two weeks, what we're going to be looking at very closely is the ability of the healthcare system to actually get this into people's veins.”