In a significant development for hereditary angioedema (HAE) patients, Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for donidalorsen, an investigational RNA-targeted therapy designed to prevent HAE attacks in individuals aged 12 and older. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2025, indicating a potential approval decision by that time.

Donidalorsen functions by inhibiting the production of prekallikrein (PKK), a protein integral to the inflammatory processes that trigger acute HAE episodes. By targeting PKK, donidalorsen aims to offer a prophylactic solution to reduce the frequency and severity of these debilitating attacks. This therapeutic approach is particularly crucial for HAE patients who, despite existing treatments, continue to experience unpredictable and potentially life-threatening swelling episodes.

The NDA submission is supported by robust data from the Phase 3 OASIS-HAE and OASISplus studies, as well as ongoing Phase 2 open-label extension (OLE) research. These studies have demonstrated that both monthly and bi-monthly dosing regimens of donidalorsen result in significant and sustained reductions in HAE attack rates. Notably, the Phase 2 OLE study reported a 96% mean reduction in attack frequency over a three-year period. Across all trials, donidalorsen was well-tolerated, with no serious treatment-emergent adverse events reported; the most common side effects were mild to moderate injection site reactions.

Dr. Brett Monia, Chief Executive Officer of Ionis Pharmaceuticals, highlighted the potential of donidalorsen to transform the prophylactic treatment landscape for HAE. He emphasized that, pending FDA approval, this would mark Ionis Pharmaceuticals’ second independent product launch, reinforcing the company’s commitment to delivering innovative therapies for serious diseases.

Hereditary angioedema is a rare genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body, including the extremities, face, gastrointestinal tract, and airway. These attacks can be painful, disfiguring, and, in cases involving the airway, life-threatening. The FDA’s acceptance of the NDA for donidalorsen, which previously received Orphan Drug Designation in 2023, represents a promising advancement for the HAE community.

In parallel, Otsuka Pharmaceutical Co., Ltd., which holds exclusive rights to commercialize donidalorsen in Europe and the Asia-Pacific region, is preparing to submit a Marketing Authorization Application to the European Medicines Agency within the year. This strategic collaboration aims to expand the availability of donidalorsen to HAE patients globally.

The announcement of the FDA’s acceptance of the NDA for donidalorsen has garnered attention within the biotechnology sector. Ionis Pharmaceuticals’ stock (Nasdaq: IONS) has shown responsiveness to such developments, reflecting investor interest in the company’s expanding therapeutic pipeline. As of the latest trading session, Ionis Pharmaceuticals’ stock closed at $38.41, experiencing a slight decrease of 0.9% from the previous close. Market analysts are closely monitoring the stock, with some projecting potential growth contingent upon regulatory approvals and successful product launches.

The progression of donidalorsen through the FDA review process underscores Ionis Pharmaceuticals’ dedication to advancing RNA-targeted therapies for rare and serious diseases. The HAE community and healthcare providers are anticipating the potential approval of this novel treatment, which could offer a new standard of care for managing this challenging condition.

Expert Insight: The Significance of Donidalorsen’s FDA Review

Experts believe that FDA’s acceptance of the NDA for donidalorsen is a pivotal step forward. He emphasized that the innovative mechanism of action targeting prekallikrein addresses a critical pathway in HAE pathophysiology. They highlighted that the sustained reduction in attack frequency observed in clinical trials offers hope for improved quality of life for patients. It has also been pointed out that the favorable safety profile of donidalorsen is encouraging, as it suggests a well-tolerated option for long-term prophylaxis.

  Brett Monia, donidalorsen, European Medicines Agency, hereditary angioedema, Inc., Ionis Pharmaceuticals, Ltd., Otsuka Pharmaceutical Co., Penn State University, RNA-targeted therapy, Timothy Craig, U.S. Food and Drug Administration