FDA Approves First in Class Therapy for of Hereditary Angioedema

The FDA has approved Dawnzera (donidalorsen) to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.

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 colds or the flu, but often episodes are difficult to predict, according to the American Academy of Allergy, Asthma and Immunology.

"People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful and dangerous breakthrough attacks even with current treatments. Durable efficacy is essential in maintaining long-term disease control,” clinical investigator Marc Riedl, M.D., clinical director, U.S. HAEA Angioedema Center; University of California, San Diego, said in a news release.

Developed by Ionis Pharmaceuticals, Dawnzera is the first RNA-targeted medicine approved for HAE, designed to target plasma prekallikrein (PKK), a key protein that activates inflammatory mediators associated with acute attacks of HAE.

Dawnzera 80 mg is self-administered via subcutaneous autoinjector once every four or eight weeks. It will be available in the next few days and has a list price of $57,642 per dose. The company expects Dawnzera to be covered by private and government insurance, and Ionis is engaging with payers to deliver timely access and development of policies for eligible patients, according to a spokesperson.

Ionis offers a free trial program with one dose of Dawnzera, as well as patient resources. All patients are eligible, including those with Medicare and Medicaid.

The approval of Dawnzera was based on positive results from the phase 3 global OASIS-HAE study. The study met its primary endpoint, with Dawnzera once every four weeks reducing monthly HAE attack rate by 81% compared with placebo over 24 weeks. Mean attack rate reduction increased to 87% when measured from the second dose, a key secondary endpoint. Additionally, Dawnzera once every four weeks reduced moderate-to-severe HAE attacks by about 90% over 24 weeks when measured from the second dose.

The study was published in May 2024 in The New England Journal of Medicine.

In an open-label extension (OLE) study, Dawnzera once every eight weeks had a similar effect. Dawnzera demonstrated 94% total mean attack rate reduction from baseline across both dosing groups after one year in the open-label extension.

The open-label study also included a switch cohort evaluating Dawnzera once every four weeks in patients previously treated with lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks. Switching to DAWNZERA reduced mean HAE attack rate by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks observed during the switch.

Across clinical studies, Dawnzera demonstrated a favorable safety and tolerability profile. The most common adverse reactions were injection site reactions, upper respiratory tract infection, urinary tract infection and abdominal discomfort.