Novartis’s alliance with Ionis Pharmaceuticals has yielded an experimental therapy that reduces levels of a protein that’s a cardiovascular disease risk factor. This drug is still in late-stage testing, but the Swiss pharmaceutical giant wants to see if its partner can produce an even better one. It’s paying $60 million to expand the partnership to another compound.
The sum announced Thursday is an upfront payment. The deal calls for Carlsbad, California-based Ionis to use its new technologies to develop a next-generation compound. Novartis is solely responsible for developing, manufacturing, and potentially commercializing this new drug.
Ionis specializes in antisense oligonucleotides, drugs that employ small pieces of DNA or RNA to bind to messenger RNA to have an effect on gene expression. The protein target Novartis is interested in is lipoprotein(a), or Lp(a). In the blood, cholesterol is carried by Lp(a), and high levels of the protein are associated with a higher risk of heart attack and stroke. Levels of this protein are set by a person’s genetics, so diet and exercise don’t have much of an effect on reducing it. Drug research efforts are underway to try a pharmacological approach at lowering Lp(a) in the blood.
Pelacarsen, the drug candidate that emerged from the Novartis/Ionis partnership, is an antisense oligonucleotide intended to reduce Lp(a) production in the liver, which in turn lowers levels of that protein in the blood. This drug is being evaluated in a Novartis-sponsored Phase 3 study enrolling 8,323 patients with cardiovascular disease. Cardiovascular outcomes data are expected in 2025.
Novartis and Ionis began their collaboration in 2017. The pharma giant paid $75 million up front and committed to pay up to $825 million more tied to the achievement of milestones. Through the end of 2022, Ionis has recorded nearly $275 million in payments from the collaboration, according to the company’s annual report. The expanded collaboration announced Thursday puts Ionis in line for milestone payments and royalties from sales of an approved therapy that would be a follow-on product to pelacarsen. Specific details of the milestone payments were not disclosed.
“This collaboration is designed to leverage Ionis’s advancing RNA-targeting platform technologies to deliver a novel Lp(a)-targeting therapy that we expect will provide industry-leading efficacy and dosing frequency,” Ionis CEO Brett Monia said in a prepared statement.
The dosing goal for the next-generation therapy was not specified, but pelacarsen is administered as a monthly subcutaneous injection. Other drug research efforts are underway to target Lp(a). Eli Lilly has reached mid-stage testing with LY3819469, a small interfering RNA (siRNA) drug that leverages a mechanism called RNA interference (RNAi). Amgen in Phase 3 with olpasiran, a siRNA drug candidate administered as a subcutaneous injection given every three months.
Meanwhile, Verve Therapeutics is developing gene-editing therapies that do their work in vivo and offer the potential for a one-time treatment. In June, Lilly inked an alliance with the Boston-based biotech, paying $60 million to start a partnership on a potential in vivo gene-editing therapy that inactivates the gene that encodes Lp(a). Lilly is funding Verve’s research and would be responsible for developing the therapy beyond Phase 1 testing. That deal puts Verve in line for up to $465 million in milestone payments.
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