Novartis’ foray into COVID-19 therapeutics hit a snag in December, when its Mesoblast-partnered cell therapy failed to help patients with a life-threatening lung injury from COVID-19. But its second effort, aimed at patients who aren’t quite as sick, is gathering steam. The Big Pharma, along with Molecular Partners, is kicking off a phase 2/3 study of its prospect in adults with early-stage COVID-19 to see whether it can ward off severe disease and hospitalization.
The duo is starting the trial two months after the National Institutes of Health announced it would test the antiviral drug, ensovibep, in hospitalized patients as part of its ACTIV-3 study.
Novartis aims to enroll a total of 2,100 patients in the trial: 400 for the dose-finding phase 2 portion and 1,700 in the phase 3 part. The study will test ensovibep in adults with COVID-19 infection confirmed by an antigen test and who experience at least two predetermined mild to moderate symptoms within a week of their diagnosis.
The companies expect the phase 2 part to read out in August this year, at which point the partners will move into phase 3. If all goes to plan, and the phase 3 data are “convincing,” Novartis will seek emergency authorization for the treatment from the FDA.
Novartis ponied up $69 million in October 2020 to collaborate with Molecular Partners on a pair of antivirals: ensovibep, also known as MP0420, and MP0423. Under the deal, Molecular Partners would carry out phase 1 trials for ensovibep and preclinical work for MP0423, with Novartis taking the lead on phase 2 and phase 3. Molecular Partners is supplying the treatments for all studies unless Novartis pulls the trigger on its license option, in which case it will pick up all further development and commercialization activities.
The pact could have an extra $165 million thrown in if Novartis takes up the option on both drugs, though Molecular Partners will forgo royalties in lower-income countries, should they gain approval, to help lower costs.
The antivirals are protein drugs based on Molecular Partners’ DARPin technology, which the company says could result in treatments that have a long half-life, may not need to be refrigerated and can be injected just under the skin. These features would be particularly important in the fight against COVID-19 in low- and middle-income countries. Although there are three antibody combinations authorized to treat COVID-19 infection, manufacturing antibodies and the challenges of administering intravenous medicines have largely limited use of existing treatments to the U.S. so far.
The rise of SARS-CoV-2 variants has raised concerns about the efficacy of authorized antibody drugs, especially single-agent treatments. Earlier this year, lab testing found that Eli Lilly's bamlanivimab alone couldn’t match a combo of bamlanivimab and etesevimab at fending off emerging coronavirus variants, leading the government to stop using it in several states where one variant was taking hold and the FDA to revoke the emergency use authorization for solo bamlanivimab. And, in May, federal officials paused shipments of the bamlanivimab-etesevimab combo to Illinois based on its reduced potency against the P.1 variant, which was first identified in Brazil.
Molecular Partners' DARPin medicines could help here, too, They can be designed to bind to multiple sites on the coronavirus and could help combat viral escape, the process through which viruses mutate and evade antibodies, the company says. Molecular Partners recently revealed preclinical results showing ensovibep “continues to retain full potency” against new variants of SARS-CoV-2, including those first identified in Brazil, California and New York.
“By virtue of its tri-specific design, ensovibep was built to resist viral mutations and indeed shows potent inhibition of all variants of concern to date, with the potential to maintain activity also for future variants,” said Molecular Partners CEO Patrick Amstutz, Ph.D., in a statement. “This type of broad spectrum activity is essential for any treatment of relevance for patients with COVID-19.”