Key Takeaways:
Ionis Pharmaceuticals Inc. (Nasdaq: IONS) and partner Biogen Inc. announced that their Alzheimer’s drug diranersen is the first tau-targeting therapy to show both a reduction in brain pathology and a cognitive benefit in a randomized Phase 2 study, sending Ionis shares up more than 8 percent.
"We are excited by these Phase 2 data, which give us the confidence to advance diranersen to registrational development," Priya Singhal, Executive Vice President and Head of Development at Biogen, said. "We believe we have seen an unprecedented and compelling confluence of efficacy and biomarkers results from a tau-directed agent in a randomized early Alzheimer’s disease study."
The topline results from the Phase 2 CELIA study, which enrolled 416 participants with early Alzheimer's, showed that diranersen demonstrated robust reductions in both cerebrospinal fluid tau and tau pathology as measured by PET scans. While the study did not meet its primary endpoint assessing dose response on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at Week 78, pre-specified analyses showed a slowing of clinical decline, particularly in patients receiving the lowest dose of 60 mg every 24 weeks.
The results mark a significant moment for Alzheimer's research, a field littered with high-profile failures. Targeting the tau protein, which forms toxic tangles in the brain, has long been a goal for drug developers. A successful therapy could unlock a multi-billion dollar market and offer hope to millions, positioning Ionis and Biogen ahead of competitors like Eli Lilly in the race for a tau-based treatment.
Diranersen is an antisense oligonucleotide (ASO) therapy, a technology pioneered by Ionis. It is designed to reduce the production of the tau protein at its source. In Alzheimer's disease, abnormal tau accumulates and forms intracellular tangles that contribute to neurodegeneration and cognitive decline. Unlike many investigational approaches that have focused on clearing extracellular tau, diranersen aims to stop the protein from being made.
The safety and tolerability profile of diranersen was generally consistent with its known profile from a Phase 1b study. The incidence of adverse events was comparable across dose groups, though a higher incidence of serious adverse events was observed at the highest dose studied.
Following the announcement, Ionis shares saw a significant uptick. The stock, which has a 1-year total shareholder return of 138.04 percent, is the subject of a bullish analyst narrative. The consensus price target of $96.73 implies a 19.8 percent upside from its recent close of $77.60, according to data from Simply Wall St. However, its price-to-sales ratio of 12.1x is elevated compared to the US Biotechs industry average of 9.7x.
Ionis's pipeline now includes 13 medicines in clinical development for neurological diseases, six of which are wholly owned. The company's financial health is also a key factor for investors; biotech drug development is capital-intensive, and a strong cash position is crucial to funding late-stage trials.
Biogen, which licensed diranersen from Ionis in 2019, will engage with regulators on the next steps to advance the therapy to a pivotal Phase 3 trial. An ongoing long-term extension study will continue to evaluate the long-term safety, tolerability, and durability of diranersen in patients with early Alzheimer's disease. The successful data provides a major de-risking event for Ionis's ASO platform and strengthens its neurology franchise.
This article is for informational purposes only and does not constitute investment advice.
