Ionis Announces Successful Phase III for HAE Candidate, Eyes FDA Submission

Ionis Pharmaceuticals is advancing its candidate drug donidalorsen, which targets RNA and is intended for hereditary angioedema (HAE), a rare and potentially fatal genetic disorder. The company recently revealed the primary findings from its Phase III Oasis-HAE study, indicating that donidalorsen significantly reduced the frequency of angioedema attacks in affected patients.

In the study, patients who received a four-week donidalorsen injection showed a highly significant reduction in attack rates with a p-value of less than 0.001, while those who received an eight-week injection had a p-value of 0.004, both compared to a placebo. The drug also achieved statistical significance across all secondary endpoints in the four-week group and on key secondary endpoints in the eight-week group.

Importantly, the trial did not report any serious adverse events associated with donidalorsen, which is an investigational ligand-conjugated antisense therapy. It works by inhibiting the production of prekallikrein, a protein essential for the activation of inflammatory mediators that trigger acute HAE attacks.

Ionis plans to present the study's data at an upcoming medical conference and is preparing to submit a New Drug Application (NDA) to the FDA, although no specific timeline has been provided. The drug has already been granted Orphan Drug status by the FDA, and efforts are underway to secure similar status in the European Union. Otsuka retains the rights to market the drug in Europe and intends to submit a marketing authorization application to the European Medicines Agency.

Kenneth Newman, the head of clinical development at Ionis, expressed optimism about the drug's potential, noting that if approved, donidalorsen could offer a new and attractive treatment option for HAE patients who often endure unpredictable, painful, and severe attacks even with existing treatments.

Ionis has been experiencing a positive trend, with its drug Wainua (eplontersen), developed in collaboration with AstraZeneca, gaining FDA approval in December 2023 for the treatment of polyneuropathy in hereditary transthyretin-mediated amyloidosis (hATTR-PN). Wainua will compete with Alnylam's two existing hATTR-PN treatments.

Ionis CEO Brett Monia highlighted the company's progress, stating that following the launch of Wainua, they are poised to independently launch additional drugs from their pipeline, with regulatory submissions planned for olezarsen for familial chylomicronemia syndrome and donidalorsen for HAE later this year.