Talking treatment: Current and future medications for HAE

Joining the 2026 Global Angioedema Leadership Conference patient track from the scientific sessions was Professor Philip Li from the University of Hong Kong. Having watched the audience enjoy their dance break, Prof Li was happy to say that with disco music, this room was cool!

Returning to serious matters, Prof Li confessed that he can only share the perspective of a doctor. He can’t know what it’s like to live with HAE. The experts in that are the people in the room, the patients and carers. He told the audience that his job today is to talk about all the medications for HAE, from established therapies that have been around for many years to drugs in clinical trials.

He started by reminding the audience that HAE is a condition defined by leaky blood vessels. It is this, he said, which causes the swelling in HAE. He showed an image of the full pathway of what happens in an HAE attack, from kallikrein at the top to bradykinin at the bottom. He admitted that this might seem complicated, but it all starts with Factor XII (12), which ignites the whole kallikrein system, beginning with pre-kallikrein, then kallikrein, and finally high molecular weight kininogen. Ultimately, this leads to the overproduction of bradykinin and to the leaky blood vessels. All therapies that are here today and in the future target something in this system, Prof Li advised. Of course, he said, there are differences in the types of HAE people have, but in types 1 and 2, there is a problem with a protein called C1 esterase inhibitor; either the body doesn’t produce enough, or it doesn’t work properly. Without enough C1-inhibitor, the system overproduces bradykinin, creating a vicious cycle of attacks.

Turning to the medicines that target this system, Prof Li started with a warning. He said that in many countries, especially in Asia, people still use a lot of anti-allergy medication, which is completely wrong. It can look like an allergy, but you cannot treat HAE with medicines for allergic reactions. At best, they do no good and can be potentially harmful.

Moving back to specific medication for HAE, Prof Li used the well-known categories: on-demand, taken when an attack has started, and preventative, which reduces or eliminates attacks.

The first treatment in the expert guidelines for HAE, which Prof Li admitted were sometimes more aspirational for patients in many countries, is C1 inhibitor, which replaces the protein that is lacking in HAE patients. C1 inhibitor can be obtained from donated blood (plasma-derived) or from rabbits (recombinant). With the latter, people who are allergic to rabbits cannot use this medicine. A potential challenge here, Prof Li said, was that the treatment is injected into the bloodstream (intravenous or IV), which can be inconvenient. However, positively, these medicines can be taken by people of all ages and in various situations, even by pregnant women.

Alternatively, instead of replacing C1 inhibitor, medicines to stop attacks can target the end problem: bradykinin. An example of this is the medicine icatibant. You can self-administer this medicine after training. The earlier you use it, the better the response and the faster the attack is resolved. Another on-demand option is ecallantide, but this is restricted to use in the US.

Moving on to preventive treatment, or prophylaxis, Prof Li said we see some IV C1 inhibitor medicines again. Some preventive treatments can be injected into body fat (subcutaneous injection), which makes it easier to administer. Therapies like lanadelumab and subcutaneous C1 esterase inhibitor are examples. Berotralstat, which Prof Li said is not currently available in China, is another preventative medicine. It is a tablet and works against kallikrein.

Back to the future

Turning to the future, Prof Li outlined how HAE management is moving increasingly towards complete control and normalization of life. He said that doctors want patients to be in control of their disease. He recalled a patient who had access to icatibant but would save the medication due to concerns about cost or reserving it for her children’s attacks, and so would often be in the hospital due to attacks. Thanks to joining a clinical trial, when she has an attack, she treats it with a pill, and the attack resolves. That’s one thing that’s new on the HAE landscape, the on-demand pill in the pocket. An option called sebetralstat is now available in some countries. Another, called deucrictibant, has shown effectiveness in trials and is awaiting approval from authorities.

‘The future of the HAE medication landscape really is personalized care.’

– Prof Philip Li, University of Hong Kong

Moving on to the latest in prevention, there is garadacimab. It is a monthly injection to prevent attacks. Another, donidalorsen, targets the prekallikrein system mentioned earlier. It uses ‘anti-sense technology’ and needs to be taken once monthly, with the potential for this to become once every two months. According to Prof Li, we get closer to the goal of normalization when people don’t have to think about their disease for long periods. He suggested these new and forthcoming treatments are effective with freedom from attacks and improved quality of life. Referring back to deucrictibant, he also suggested this oral medicine may be effective as a preventive, with trials ongoing. Finally, he mentioned the potential of gene therapy to eliminate the problems of the kallikrein system, although this may sound scary. For people in current clinical trials, it has made a huge difference.

Recounting another patient, Prof Li explained how personalized care means understanding what each patient needs and wants. In China, he said, there is reluctance among some to take Western medicine in pills due to a belief that it damages the liver. In one patient, this meant she stopped taking one of the latest oral medications, leading to a return to many attacks. By talking with and understanding the patient, they found a solution. This patient moved to an injectable medicine, which was much more acceptable and led to her becoming attack-free.

In closing, Prof Li praised the advocates in the room for their hard work. He said that the work of the Hong Kong Member Organization is the only reason patients have reimbursed medication.

‘HAEi Member Organizations are the engine of change.’

– Prof Philip Li, University of Hong Kong