It’s not often that high profile pharmaceutical executives publicly laud a direct competitor’s medicine, but that’s what’s happening these days for Pfizer’s COVID-19 antiviral Paxlovid.
“The Pfizer compound was developed kind of from whole cloth during the course of the pandemic,” said Eli Lilly CEO David Ricks, during an interview for Fierce JPM Week. “Small molecule drug development is a tricky business, and it involves as much art as science sometimes, so hats off to them.”
That sentiment was echoed by Jay Bradner, M.D., president of the Novartis Institutes for BioMedical Research, the Swiss pharma's R&D engine.
“The Pfizer medicine is a remarkable contribution,” Bradner said. “I mean, to take an inhibitor designed for a completely different virus, and then boost what is a peptide-like inhibitor … with a second drug to prevent its disposal, I think it's a pretty heroic act of repurposing, and the activity of the molecule is quite breathtaking.”
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Paxlovid won authorization in November 2021 for recently infected individuals who are at a high risk of progressing to a severe form of the disease. The pharma giant has already booked orders from the U.S. and U.K. governments for millions of courses.
The oral treatment added to the feather already in Pfizer’s cap from the COVID-19 vaccine Comirnaty. Together, the products make up a franchise that didn’t even exist in the pharmaceutical world before 2020.
Analysts with SVB Leerink expect $24.2 billion in revenue from Paxlovid this year, potentially pushing the company over the edge of $100 billion in total revenue. Comirnaty, meanwhile, will pitch in $29.7 billion, according to their estimates.
So where does that leave Eli Lilly and Novartis?
Ricks know his company’s role. The Indianapolis-based Big Pharma was one of the first out the gate with the antibody treatment bamlanivimab for mild to moderate COVID-19 or for post-exposure prophylaxis in high-risk individuals.
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“Clearly, an oral medication that could do something similar to an antibody would be a much more attractive product,” Ricks said. “And so our point of view is that antibodies are much easier to develop rapidly early in pandemic response.”
The formula had to be tinkered with as the variants tested its efficacy. Lilly added in etesevimab in a combo treatment, which kept the therapy in use and helped book a $1.3 billion buy from the U.S. government in November 2021. Lilly has since found the combo is less effective against the latest omicron variant, which Ricks acknowledges.
“It's very active against delta but does not preserve full activity against omicron,” he said.
That doesn’t mean Lilly is out of the game, because the Bam/Eddy combination, as they’ve nicknamed it, isn’t all that has come out of the Big Pharma’s R&D shop. Ricks said Lilly is well suited with the capacity and skill to continue to engineer antibodies quickly as needs in the pandemic shift.
"We'd always prefer to have an oral for cost and accessibility, convenience reasons," Ricks said. "And it turns out that one of the orals has efficacy results that are in the ballpark of antibodies, so I think probably their use will diminish through time.”
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The company has submitted baricitinib, also known as the Incyte-partnered rheumatoid arthritis drug Olumiant, for a full label approval in COVID-19 patients. The drug was previously authorized for emergency use and, according to Ricks, has become the standard of care for ventilated patients. Lilly found that it reduced the risk of death 46% in late-stage patients.
But that’s not all. “Early last year our scientists had the foresight to develop a third antibody,” according to Ricks. Bebtelovimab is an antibody that has so far shown full activity against omicron and all other known variants of concern.
Lilly is also seeking to address another pandemic challenge with this third candidate. Bebtelovimab can be administered at a much lower dose than its predecessors, and quickly too.
“The challenge with 30 to 60 minute infusions right now is the capacity and accessibility to infusion sites during big outbreaks,” Ricks said. “This has the potential to be administered in less than a minute.”
That uses fewer resources, which, amid the omicron surge, have been hard to come by.
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Lilly has submitted bebtelovimab for an emergency use authorization and is anticipating a swift review. The company is already stockpiling hundreds of thousands of doses to be ready for the FDA go-ahead, Ricks said.
For his part, Bradner said Novartis always knew his company wouldn’t be able to offer anything to the vaccine hunt after the Swiss pharma sold its vaccines unit to GlaxoSmithKline many years ago.
“We have this term we borrow from major league hockey: skate to where the puck is going,” Bradner said. And that, for Novartis, meant antivirals. “We imagined the doomsday scenario that repurposing or mechanistic repositioning of medicines might be inadequate, that the virus might mutate. And that the vaccines would ultimately prove important, but not definitive.”
But Novartis didn’t exactly have medicines kicking around that could be repurposed, like Gilead did with remdesivir, now called Veklury.
“We looked on the shelf, believe me,” Bradner said.
That led Novartis to pour resources into one internal project and one external effort. The company doubled down on that external antiviral collaboration with Molecular Partners during the J.P. Morgan Healthcare Conference after the candidate, ensovibep, was linked to a 78% risk reduction in an earlier-stage population. The medicine has also shown promise against omicron.
The internal project is a pan-coronavirus inhibitor, which Bradner said could someday best Paxlovid. That medicine should soon enter human clinical trials. The Novartis offering could help “in a broader use scenario,” according to Bradner, as Paxlovid may not be tolerated by all, could have reactions with other medicines and so on.
“This is a molecule invented for this virus and it should, in the fullness of time, be maybe 100 times more potent even than the remarkable medicine from Pfizer today,” Bradner said. “It is indeed an insurance policy against you know, God forbid, a zeta virus, or whatever might come next.”