AstraZeneca dumps Ionis drug despite hit in phase 2 cholesterol trial

Good, but not good enough. That is the verdict AstraZeneca reached after seeing phase 2b data on its Ionis Pharmaceuticals-partnered cholesterol drug ION449, which comfortably beat placebo but fell short of the bar for further development.

Ionis designed the antisense therapy ION449 to reduce plasma levels of PCSK9 and, by extension, lower low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. AstraZeneca, having licensed the asset in 2015, put the hypothesis to the test in the phase 2b SOLANO clinical trial. The study randomized 411 people to receive subcutaneous doses of ION449, also known as AZD8233, or placebo once a month.

ION449 achieved a 62.3% reduction in LDL-C after 28 weeks compared to placebo, causing the study to hit its primary endpoint with a p-value of 0.001. However, the results fell short of AstraZeneca’s efficacy criteria. As such, the Big Pharma opted against moving the drug candidate into phase 3.

Neither AstraZeneca nor Ionis have shared more data or insights from the trial, beyond a statement that ION449 was generally safe and well tolerated, or detailed what bar the candidate needed to clear to get the green light to move into phase 3. But an earlier, smaller phase 2 trial provides a pointer to the level of efficacy AstraZeneca may have hoped to see. 

In the earlier, 119-subject study, AstraZeneca linked the antisense oligonucleotide to LCL-C reductions of up to 79%, at the 90-mg dose, from baseline. The 50-mg dose achieved a 73% reduction. LDL-C in the placebo arm fell 2%.

AstraZeneca tested a 60-mg shot in SOLANO but failed to match the efficacy seen at the lower dose in the earlier study.

While AstraZeneca has walked away from ION449, it remains partnered with Ionis on a clutch of other therapies, including the chronic kidney disease prospect ION532, the nonalcoholic steatohepatitis assets ION839 and ION455 and the cancer candidate ION736.