Ionis Pharmaceuticals once had AstraZeneca involved with and spied a bright future for PCSK9 inhibitor ION449. Now, after the U.K. pharma backed out last year, CEO Brett Monia, Ph.D., thinks the drug may have missed its shot.
“PCSK9 is not a good match for us to bring forward through development,” Monia said in an interview with Fierce Biotech Wednesday morning ahead of the company’s presentation at the J.P. Morgan Healthcare Conference. “The investment in phase 3 is massive.”
Monia said the therapy will be hard to partner again due to the competition in the field and the strenuousness of planning a phase 3 trial. The reason for that, Monia explained, is that you likely need to conduct a cardiovascular outcomes trial to get payers to rally behind the drug. That’s time and money the company doesn’t want to put up. He added that a head-to-head comparison trial would also likely be needed to really win over the market.
AstraZeneca elected to walk away from ION449 in November after getting a look at phase 2b data in patients with hypercholesterolemia. If Ionis can’t find another partner, it’s likely to fall out of the pipeline.
“It really is a good-looking drug, it just probably came a little bit too late to the game,” Monia said. The drug would face rival therapies such as Sanofi and Regeneron's Praluent and Amgen's Repatha.
It’s a different story for fesomersen, which was returned to Ionis from Bayer after being tested in patients with end-stage renal disease. Monia says that there’s been greater interest in the factor XI drug compared to ION449, given the quality of the drug and market competitiveness.
Although Ionis has received inbound interest, Monia said locking up a new partnership this quarter would be too aggressive of a timeline given the med was just returned in the third quarter of 2022.
“Partnerships like these have a gestation period of usually about a year,” he said.
The diverging paths of ION449 and fesomersen come as Ionis is bracing for three new commercial products, furthering Monia’s goal of making Ionis a fully integrated biotech company rather than a licensing behemoth.
Included among the three is tofersen, a Biogen-partnered treatment for SOD1 amyotrophic lateral sclerosis. The FDA action date was pushed back in October 2022 from late January to late April, and an advisory committee meeting has not yet been scheduled, although Monia says he’s expecting and hoping for one.
The drug failed a phase 3 trial in 2021, but included in the approval application were 12-month data showing clinical improvements and better quality of life when tofersen was administered earlier.