FDA green lights CSL's once-monthly HAE drug Andembry
CSL has FDA approval for its new drug to prevent hereditary angioedema (HAE) attacks, Andembry, offering a new, first-in-class option for patients with the rare genetic disorder.
Factor XIIa inhibitor Andembry (garadacimab) has been cleared in the US for use in patients aged 12 and over with HAE, which affects about 1 in 10,000 to 1 in 50,000 people worldwide and leads to unpredictable bouts of debilitating and painful swelling in various parts of the body.
The drug has previously been approved in other markets, including the EU, UK, Japan, and Australia, and according to CSL is the only HAE treatment to offer once-monthly dosing from the start for all patients.
Andembry is administered subcutaneously using an auto-injector pen and provides less frequent dosing than Takeda's $1.2 billion-selling kallikrein inhibitor Takhzyro (lanadelumab), which requires a subcutaneous injection every two weeks.
It also offers an alternative to Biocryst's daily oral kallikrein inhibitor Orladeyo (berotralstat), which was cleared in the US in 2020 and is predicted to make up to $600 million in sales this year.
CSL's head of R&D, Bill Mezzanotte, said Andembry is the first monoclonal antibody discovered and developed entirely by the company and "offers people living with this life-threatening condition long-term control over their disease along with a convenient administration method."
Andembry was shown to reduce the average number of monthly attacks by 86.5% compared to placebo in the VANGUARD study reported in 2023, with almost two-thirds of patients (61.5%) taking CSL's drug attack-free over the six-month study period compared to zero in the control group.
The drug is a successor to its older HAE prevention products Berinert (C1 esterase inhibitor), given intravenously, and follow-up Haegarda, which is given twice weekly as a subcutaneous injection, which made $127 million and $247 million, respectively, in the first six months of CSL's current fiscal year.
Other competitors are on the horizon, including Intellia's gene-editing drug lonvoguran ziclumeran (formerly NTLA-2002) that could offer a one-shot strategy for long-term protection against HAE attacks and recently started phase 3 testing.
There's also a long-acting kallikrein inhibitor from Astria Therapeutics in late-stage testing, called navenibart, that could offer dosing every six months, while Ionis has filed for approval of antisense-based therapy donidalorsen, which targets prekallikrein, with an FDA verdict due by 21st August.
Pharvaris, meanwhile, is developing two oral formulations of bradykinin B2 receptor antagonist deucrictibant, one for on-demand treatment of HAE attacks and the other for prevention.
KalVista drug for acute attacks delayed
Also this week, KalVista Pharma revealed that the FDA review of its oral kallikrein inhibitor sebetralstat, vying to become the first US-approved treatment for oral, on-demand treatment of HAE attacks, has been delayed.
The company said that the FDA – which has seen swingeing job cuts under the Trump administration – has said it will be unable to meet its 17th June deadline for the review "due to heavy workload and limited resources." The FDA indicated that it expects to deliver a decision within approximately four weeks.
Photo by Diana Polekhina on Unsplash
