6 Treatment Options for Hereditary Angioedema

The swelling and other symptoms that come with hereditary angioedema (HAE) occur because of too much of a substance called bradykinin. There are several treatment options to help lower the production of or block the actions of bradykinin. Some medicines you take when you need them. These are called on-demand therapies. Others, called prophylactics, work to prevent episodes so they happen less often. Pairing these approaches can be an even more effective way to control HAE.

Excess bradykinin happens when you don’t have enough of a protein called C1 esterase inhibitor (C1-INH). That’s why HAE is also known as C1 inhibitor deficiency. Drugs in this class work by filling in for the C1-INH you’re missing. You’ll take these replacement medicines at the first sign of an attack. They’re delivered through an IV you set up yourself or by injection. Your doctor, or a nurse, will show you how to do both.  C1 esterase inhibitors for HAE include:

• Berinert
• Ruconest

C1 esterase inhibitors approved by the FDA for prevention of HAE episodes include:

• Cinryze
• Haegarda

These stop acute HAE attacks by blocking the protein receptor that responds to bradykinin. When this receptor is blocked, excess bradykinin can’t relax your blood vessels, which is what triggers swelling. Only one medication works this way. It’s called icatibant (Firazyr, Sajazir), and you inject it yourself. 

Kallikrein inhibitors treat HAE by blocking an enzyme called kallikrein. When you don’t have enough C1-INH, it’s kallikrein that makes too much inflammatory bradykinin. One medicine in this class, donidalorsen, blocks an RNA precursor of kallikrein called prekallikrein. You inject these drugs or take them as a pill. Kallikrein inhibitors used on demand to treat acute HAE attacks include:

• Ecallantide (Kalbitor)
• Sebetralstat (Ekterly)

Kallikrein inhibitors used to prevent HAE episodes include:

• Berotralstat (Orladeyo)
• Donidalorsen (Dawnzera)

Factor XIIa is at the top of the pathway that leads to excess bradykinin. Factor XIIa inhibitors stop the whole cascade before it starts. Only one medicine for HAE works this way. It’s called garadacimab (Andembry). You’ll inject it once a month for prevention.

Antifibrinolytics help blood clot by stopping the body from breaking down a protein called fibrin. They’ve been used to treat HAE, but they don’t always work. And when they do, experts aren’t sure how. Given new and more effective options, their use for HAE has fallen out of favor. Antifibrinolytics prescribed for HAE in the past include aminocaproic acid and tranexamic acid.

These increase the levels of C1 inhibitors but in a less specific way than today’s targeted medicines. While steroids can help ward off HAE attacks, they don’t work right away or on demand. Long-term use of androgens also comes with side effects, including liver toxicity, high cholesterol, obesity, and more. Anabolic steroids formerly used for HAE include:

• Danazol
• Oxandrolone
• Stanozolol

Most HAE attacks happen spontaneously for reasons that aren’t well understood. But it can help to identify possible triggers, especially if lifestyle changes can be made to avoid them. Everyone is different, but HAE triggers include:

• Physical trauma
• Mental or emotional stress
• Medications, such as ACE inhibitors or estrogen-containing medicines
• Infection

Researchers continue to look for more ways to treat HAE. Drugs being studied include:

• Deucrictibant, a new bradykinin B2 receptor antagonist
• NTLA-2002, a gene-editing system
• Navenibart (STAR00215), a monoclonal antibody or biologic

To find a clinical trial near you, ask your doctor or go to clinicaltrials.gov and search for “hereditary angioedema.” The U.S. Hereditary Angioedema Association is also a good resource for clinical trials and the latest treatments.

You and your doctor will work together to figure out the best way to manage your HAE. How often attacks occur and the severity of your symptoms should be considered. At the very least, everyone with HAE needs an on-demand treatment that can stop acute attacks. Talk to your doctor about adding a long-term preventive medicine to limit episodes.