FDA Sets Goal Date for Donidalorsen in HAE

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Ionis Pharmaceuticals Inc. announced today in a news release that the FDA has accepted a new drug application (NDA) for donidalorsen, an investigational RNA-targeted medicine to prevent hereditary angioedema (HAE) attacks in adult and pediatric patients ages 12 and older. The Prescription Drug User Fee Act (PDUFA) date is set for August 21, 2025.

HAE is a rare genetic disorder caused by a dysfunction in the C1 esterase inhibitor (C1INH) protein, which is part of a group of proteins in the body’s immune system. As a result, periods of severe and sometimes deadly swelling can occur in the limbs, face, intestinal tract and airway. Episodes may be triggered by anxiety, medical procedures or illnesses such as cold or flu but often episodes are difficult to predict, according to the American Academy of Allergy, Asthma and Immunology.

Donidalorsen interrupts the pathway that leads to HAE attacks. It works by reducing prekallikrein production, which activates inflammatory responses associated with HAE.

“Despite currently available treatments, many people living with HAE continue to experience painful and potentially life-threatening breakthrough attacks,” Brett Monia, Ph.D., CEO of Ionis said in the release.

The application for donidalorsen was based on positive results from the phase 3 OASIS-HAE and OASISplus (open label extension and switch) studies and the ongoing phase 2 OLE study.

Study data from OASIS-HAE was posted in May 2024 in The New England Journal of Medicine. Participants were either given placebo or 80 mg of donidalorsen subcutaneously every four or eight weeks for 25 weeks. By week 25, the mean HAE attack rate was 87% lower in the donidalorsen than in the placebo group. The most common adverse reactions were erythema at the injection site, headache and nasopharyngitis with 98% of adverse events being mild to moderate.

Ionis presented results from the phase 3 and phase 2 OASISplus OLE studies at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Annual Scientific Meeting held in Boston from Oct. 24-28. Ionis reported that donidalorsen reduced HAE attacks by a mean of 96% over three years. A total of six posters were presented, including research examining the burden of HAE disease cost which can average nearly $200,000 in expenditures yearly.

The FDA granted donidalorsen Orphan Drug Designation in 2023.

Donidalorsen joins sebetralstat as another HAE treatment accepted by the FDA as an NDA. The PDUFA goal date for sebetralstat is June 17, 2025.