Ionis Pharmaceuticals announced this morning that it is pivoting from its original drug candidate for prion disease, ION716, to a new drug candidate. Ionis reaffirmed its commitment to developing a drug for prion disease, and stated a current goal of launching human trials in late 2022.

As background, we have worked with Ionis since 2014 on establishing proof-of-concept for using their antisense oligonucleotide (ASO) technology to lower PrP in the brain as a therapy for prion disease. Together, we found robust evidence that PrP-lowering ASOs are effective against prion disease in mouse models [[Raymond 2019], [Minikel 2020]]. For the past couple of years, Ionis has been very public about its commitment to prion disease. They have sent their scientists to attend prion disease conferences, featured the program at their investor day, and, until they stopped disclosing preclinical programs altogether at the end of 2020, had listed the program on their website’s pipeline page.

Last year, Dr. Anne Smith told CJD Foundation Family Conference attendees that Ionis had identified a promising ASO candidate for prion disease, ION716, and that their goal was to get it into human trials by the end of 2021. But that ASO was still in preclinical studies at the time. FDA guidance requires a large amount of animal pharmacology and toxicology data to qualify a drug candidate for an Investigational New Drug (IND) application. In addition to fulfilling FDA requirements, these preclinical studies also offer an opportunity for a company to decide whether they’re confident they have the best candidate for advancing into humans. In this case, Ionis found rationale to pivot to a different compound. The fundamental parameters of Ionis’s program will remain the same: the new drug candidate is still an ASO, targeting the PRNP RNA, to be delivered via lumbar puncture.

Today’s announcement is good and bad news. The good news is, Ionis seems to have found a candidate it likes better than ION716. The bad news is, whereas we’d previously heard trials might begin this year, it’s now looking more like late 2022. That’s disappointing, but we always knew drug development is not a straight path from A to B, and we expected twists and turns. The important thing is, they remain committed to developing a drug for prion disease.

The announcement today is unrelated to the recent halting of a Huntington’s disease ASO trial. That halting was ordered by an independent data monitoring committee, and that trial was being run by Ionis’s partner Roche. Ionis says that they still do not have any further detail on what happened in that trial, and have no reason to suspect a “platform issue”, meaning a problem that would affect other drug candidates in their pipeline.