EU approves Otsuka's long-acting HAE drug Dawnzera

The European Commission has approved Otsuka's Dawnzera for the prevention of recurrent attacks in rare disease hereditary angioedema (HAE), a drug that can be self-administered by patients with weeks between doses.

Dawnzera (donidalorsen) is a first-in-class antisense oligonucleotide-based plasma prekallikrein (PKK) inhibitor that was approved in the US last year and was originally developed by Ionis. PKK activates inflammatory mediators associated with attacks – unpredictable bouts of debilitating and painful swelling around the body – that characterise HAE.

Otsuka licensed exclusive European rights to the drug in 2023 for $65 million upfront, plus milestone payments based on regulatory and sales targets, and will pay royalties on sales of up to 30% to Ionis. Later, it expanded the agreement to include Asia-Pacific markets, where it has yet to be approved. The EMA decision sparks a $15 million milestone payment to Ionis.

The EMA has cleared Dawnzera for use in HAE patients aged 12 and over based on clinical trials that showed the drug was able to reduce the monthly attack rate by 81% with dosing every four weeks and 55% when it was administered every eight weeks.

In an open-label extension study, the drug achieved a 94% overall mean monthly attack rate reduction at one year.

For comparison, CSL's recently approved Factor XIIa inhibitor Andembry (garadacimab) is dosed monthly, while Takeda's blockbuster kallikrein inhibitor Takhzyro (lanadelumab) requires injections every two weeks. An oral alternative, BioCryst Pharma's Orladeyo (berotralstat), is also available and requires daily dosing.

According to Otsuka, HAE affects around 15,000 people in Europe, while Ionis has said it believes there are around 7,000 patients in the US, of whom three-quarters need prophylactic treatment. Ionis has predicted that global sales of the drug could top $500 million a year by the early 2030s.

"As the first and only RNA-targeted therapy for HAE, we believe Dawnzera has the potential to become the prophylactic therapy of choice for many patients across the EU," commented Ionis' chief executive, Brett Monia.

Earlier this month, Ionis said that the drug had seen prescriptions written for all patient segments in the US since launch, with a growing number of repeat prescribers.

There was more good news for patients with HAE last year when KalVista Pharma claimed approval for its kallikrein inhibitor Ekterly (sebetralstat), the first oral therapy that can be used as an on-demand therapy when patients experience an acute attack.