Ionis Reports Positive Phase 3 Results for Donidalorsen in Hereditary Angioedema Study

Ionis Pharmaceuticals has announced promising topline results from their Phase 3 OASIS-HAE study focusing on the treatment of hereditary angioedema (HAE) with the investigational drug donidalorsen. The study achieved its primary goal by significantly decreasing the frequency of HAE attacks in participants who received donidalorsen injections every 4 or 8 weeks, compared to those who were given a placebo. The statistical significance was found with p-values less than 0.001 for the 4-week dosage group and 0.004 for the 8-week dosage group. Additionally, all secondary endpoints were met in the 4-week group, and key secondary endpoints were achieved in the 8-week group, indicating a robust efficacy profile for donidalorsen.

Hereditary angioedema is a rare genetic disorder that leads to severe and unpredictable swelling in various parts of the body, including the skin, gastrointestinal system, and upper respiratory tracts. Donidalorsen is designed to target and suppress the production of prekallikrein (PKK), an enzyme that plays a crucial role in the pathway that triggers HAE attacks.

The safety and tolerability of donidalorsen were well-supported by the study results, with no serious adverse events reported among patients who received the treatment. This positive safety profile, combined with the drug's efficacy, makes donidalorsen a promising candidate for addressing the unmet need in HAE treatment, where current prophylactic treatments may not fully prevent severe and painful attacks.

Based on these encouraging results, Ionis is preparing to submit a New Drug Application (NDA) to the U.S. FDA. Additionally, Otsuka, which holds commercial rights for donidalorsen in Europe, plans to submit a Marketing Authorization Application to the European Medicines Agency. Donidalorsen has already received Orphan Drug Designation in the United States, and a similar designation process is underway in the EU.

Kenneth Newman, M.D., the senior vice president and head of clinical development at Ionis, expressed optimism about the potential of donidalorsen to provide a new and effective treatment option for HAE patients. He highlighted the significance of the data from the Phase 3 study and ongoing Phase 2 open-label extension study, suggesting that donidalorsen could significantly improve patients' quality of life.

Ionis CEO Brett P. Monia, Ph.D., emphasized the consistent positive outcomes from multiple Phase 3 trials over the past year, showcasing the strength of Ionis' LICA platform for RNA-targeted therapies. He remarked on the company's commitment to advancing their pipeline of innovative treatments, which includes not just donidalorsen but also other promising candidates.

The Phase 3 OASIS-HAE study, characterized as a global, multicenter, randomized, double-blind, placebo-controlled trial, enrolled 91 participants aged 12 and above with Type 1 and Type 2 HAE. Participants were randomized to receive either donidalorsen or a placebo in a 2:1 ratio. The primary endpoint was based on the reduction of HAE attack frequency from week one to week 25.

Following the 24-week treatment period, over 90% of patients continued into the Phase 3 OASIS-Plus open-label extension study, designed to evaluate long-term safety and efficacy. The OASIS-Plus study also included a cohort of patients who switched from other prophylactic HAE medications to donidalorsen, further assessing its long-term benefits.

Overall, the positive outcomes from the Phase 3 studies of donidalorsen mark a significant step forward in HAE treatment and reflect Ionis Pharmaceuticals' dedication to delivering transformative therapies for patients with severe and rare diseases.