In Ionis Pharmaceuticals Inc.’s second U.S. FDA approval in under a year, the agency approved Dawnzera (donidalorsen) as a prophylactic therapy in the rare and genetic disease hereditary angioedema (HAE). 

The approval came as targeted as the NDA had a PDUFA date of Aug. 21. 

Dawnzera now joins a market with previously approved drugs for the rare, genetic, life-threatening condition, as well as other companies with HAE drugs in development.

The ligand-conjugated antisense targeting the prekallikrein mRNA is designed to prevent HAE attacks. Swelling is a dominant symptom, including the neck and hands, and it affects about 7,000 people in the U.S. About 25% of those diagnosed with HAE do not have a family history of the disease. 

Kyle Jenne, Ionis’ chief global product strategy officer, said on a call soon after the approval was announced, that the cost of the treatment will be start at about $740,000 annually. Dawnzera comes with an autoinjector for dosing that starts at a recommended every four weeks but may be stretched to every eight weeks. It takes about 10 seconds to self-administer. 

The price per dose is on par and competitive with some competitor prices, according to Ionis. 

Company executives said they expect the majority of HAE patients will start on the recommended four-week dosing and possibly move on to eight-week administrations. 

Brett Monia, Ionis’ CEO, told investors that the company thinks of the U.S. as a predominantly switch market, based on what it perceives as a large amount of dissatisfaction by patients using other HAE treatments. He cited Dawnzera’s self-administration as a big plus, along with the potential eight-week dosing option.

Monia added that he expects Dawnzera to be available within the week. 

The approval was based on positive results from a phase III global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE study, which hit its primary endpoint. Dawnzera significantly reduced participants’ monthly HAE attack rate by 81% compared to placebo over 24 weeks. 

The mean attack rate reduction increased to 87% when measured from the second dose, which was a key secondary endpoint. The treatment also reduced moderate to severe HAE attacks by about 90% over 24 weeks when measured from the second dose.

This is the second FDA approval for the Carlsbad, Calif.-based company in the past 12 months. In December 2024, the agency cleared the company’s Tryngolza (olezarsen) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), a rare form of severe hypertriglyceridemia that can lead to life-threatening acute pancreatitis.

The antisense oligonucleotide targeting mRNA for apolipoprotein C-III is the first-ever FDA-approved treatment that significantly and substantially reduces triglyceride levels in adults with FCS and provides clinically meaningful reduction in AP events when used with an appropriate diet (≤20 grams of fat per day). The drug is self-administered with an autoinjector once monthly.

The competition

The FDA approved in July Kalvista Pharmaceuticals Inc.’s Ekterly (sebetralstat) for HAE in those ages 12 and older. Ekterly is the first orally delivered on-demand treatment, as all others in the U.S. are intravenously or subcutaneously administered.

The FDA approved CSL Behring LLC’s humanized anti-factor XIIa monoclonal antibody, Andembry (garadacimab), in June to prevent HAE attacks in those ages 12 and older. The go-ahead followed green lights for the compound in other major markets. In January, regulatory authorities in Australia and the U.K. gave their blessings, followed by approvals in the EU, Switzerland, Japan and the United Arab Emirates.