The U.S. just had another COVID-19 drug authorized for emergency use. But the approval is limited—and, with at least one vaccine launch on the horizon, industry watchers wonder whether drugs to treat the illness have any staying power.
The FDA authorized Eli Lilly’s bamlanivimab for emergency use on Monday, making it the first antibody therapy to win that distinction. Dubbed LY-CoV555, it's an anti-SARS-CoV-2 antibody therapy the Indianapolis pharma is co-developing with AbCellera.
The OK comes with some caveats: It's limited to patients 12 years and older who aren't hospitalized but who are at high risk of developing severe illness, including elderly people and those with certain underlying conditions. And Lilly is advising infusion within 10 days of symptom onset.
Lilly said it will immediately start shipping the drug to distributor AmerisourceBergen, and it expects to manufacture up to 1 million doses of the single-dose therapy by the end of 2020. The U.S. government secured 300,000 doses in a recent $375 million deal and will handle allocating it to providers around the country.
The complex definition of “high risk,” as laid out in an FDA fact sheet, has one industry watcher complaining.
"We expect this limited indication to be highly confusing to the community physicians and urgent care centers that see many COVID cases, and even in nursing homes and hospital ERs this labeling and the determination of risk will be confusing," SVB Leerink analyst Geoffrey Porges wrote in an investor note Tuesday.In clinical trials, Lilly found that patients with an inadequate early immune response to the virus were likely to have higher viral loads and a higher risk of hospitalization—and were thus the most likely to benefit from antibody treatment, Porges noted. But there is no word on how testing for viral load or immune response could be applied in the real world, he added.
Bamlanivimab was discovered by AbCellera and scientists at the National Institute of Allergy and Infectious Diseases (NIAID) in a blood sample from one of the first U.S. patients who recovered from COVID-19.
The drug is not omnipotent when it comes to treating COVID-19. The NIAID recently scrapped the bamlanivimab portion of a phase 3 trial in hospitalized patients after an independent data monitoring panel found it was unlikely to improve outcomes over placebo.
Even the trial data underpinning the emergency use authorization—interim results from the ongoing phase 2 Blaze-1 trial—showed mixed results. For instance, the drug didn’t top placebo at clearing the virus by Day 11, which was the study’s primary endpoint.
Plus, the fact that the highest dose tested performed even worse than the middle dose is simply confusing.
The current approval is for the lowest dose tested, 700 mg. The drug did cut the risk of hospitalizations and emergency room visits within 28 days after treatment to about 3%, from placebo’s 10%, among high-risk patients. The FDA pointed to that benefit as “the most important evidence that bamlanivimab may be effective.”
Using an antibody to turbocharge the immune system to fight the novel coronavirus is an idea widely explored by many biopharma companies. Perhaps the most well-known among them is Regeneron, whose antibody cocktail, called REGN-COV2, was used as part of President Donald Trump’s treatment after he caught the virus.
Regeneron has also asked the FDA to authorize REGN-COV2 for emergency use in outpatients. Results from a phase 2/3 clinical trial linked the antibody cocktail to a 57% decrease in medical visits within 29 days after treatment, with the effect more pronounced in high-risk patients.
The Regeneron therapy also beat placebo at reducing viral load through Day 7. However, the drug recently hit a snag with a trial in hospitalized patients: An independent data monitoring committee recommended halting enrollment of severely ill patients because of safety concerns.
Lilly has its own antibody combo, too—bamlanivimab paired with etesevimab (LY-CoV016/JS016), which it licensed from China’s Junshi Biosciences. In Blaze-1, the duo reduced viral load, clinical symptoms, COVID-19-related hospitalizations and ER visits. Lilly plans to request an emergency authorization for the combo as early as this month, Lilly Chief Scientific Officer Daniel Skovronsky, M.D., Ph.D., told investors on a conference call in late October.
Now that bamlanivimab has won an emergency use authorization, Lilly needs to move carefully with manufacturing to ensure supply. An FDA inspection a year ago at the company’s Branchburg, New Jersey, facility, found inadequate “control of computer systems,” including deleted manufacturing data, Reuters reported. The site is one of five plants that make the antibody drug. Although the problem wasn’t tied to the COVID-19 treatment, a potential FDA warning letter could hurt output.
Under the FDA authorization, Lilly will set up an independent third party to review batch records and other data related to bamlanivimab quality at the Branchburg site. Apart from its internal capacity, Lilly has tapped the likes of Amgen and Fujifilm Diosynth Biotechnologies to help scale up manufacturing.
Besides the anti-SARS-CoV-2 antibodies, Lilly’s rheumatoid arthritis med Olumiant is also under FDA review for emergency use in hospitalized COVID-19 patients. Adding the JAK inhibitor to Gilead Sciences’ Veklury, also known as remdesivir, further reduced time to recovery by 12.5% and improved the odds of clinical improvement, according to data from the NIAID-run ACTT-2 trial.
Bamlanivimab marks the fourth COVID-19 drug the FDA has authorized for emergency use during the pandemic.
Veklury recently turned its emergency nod to an official approval for all hospitalized COVID-19 patients, but the broadly inclusive label has drawn controversy as the antiviral has shown very little benefit for moderately ill patients.
Anti-malaria drug chloroquine, a drug touted by Trump during the early days of the pandemic, had its emergency authorization revoked after clinical data proved it lacked antiviral effects. The FDA’s emergency nod for convalescent plasma also sparked debate.
While therapeutics represent important weapons in the fight against COVID-19, their commercial value may be dwindling now that Pfizer and partner BioNTech have unveiled positive early COVID-19 vaccine news, saying their BNT162b2 was more than 90% effective in preventing the disease at an interim analysis.
An effective vaccine would mean fewer COVID-19 patients, squeezing the market for treatments. Therefore, it “should raise further questions around the mid-to-long-term durability of those revenue streams,” analysts at Barclays wrote in a Monday note to clients.
Lilly CEO David Ricks defended the need for its antibody options during an interview with CNBC's "Squawk Box" on Tuesday. “Even in well-controlled [other] respiratory illness ... we still have vaccination and antibody therapy because some patients escape the vaccine and still get the condition, and they need to be managed with a therapy,” he said. “This will be useful in the long term, hopefully at much lower volumes” later.
Lilly’s antibodies might be able to carve out a piece of the preventive market, though. The company is testing bamlanivimab’s ability to protect people against coronavirus infection in the phase 3 Blaze-2 study in residents and staff at long-term care facilities.
Editor's Note: This story has been updated to clarify that the EUA has detailed definition of "high risk."