Before 2008, treatment options for hereditary angioedema were limited. Now there are eight FDA-approved medications and even more promising therapies on the horizon.

Hereditary angioedema (HAE) is a rare chronic disorder that affects your immune system. This genetic condition involves a mutation in the C1 esterase inhibitor gene. It causes unpredictable attacks of severe swelling in your arms, legs, hands, feet, intestinal tract, face, and airway.

Although the symptoms of HAE can be similar to those of an allergic reaction, HAE requires different treatment.

There’s no cure for HAE. But researchers are developing a growing number of on-demand therapies to lessen the length and severity of these life threatening attacks and help prevent them from happening.

Learn more about the newest treatments and promising avenues of research.

If you have HAE, you most likely don’t have enough C1-inhibitor protein or, if you have it, the protein does not work as it should. That causes another protein, plasma kallikrein, to become overactive. As a result, you produce more bradykinin, a substance that plays a role in inflammation and can cause an HAE attack.

Kallikrein inhibitors work by binding to kallikrein and preventing the overactivity that triggers attacks. There are currently two kallikrein inhibitors that work to prevent attacks and one you can use when symptoms occur.

Lanadelumab-flyo (Takhzyro)

In 2018, Takhzyro became the first kallikrein inhibitor approved to prevent HAE attacks in adults and children ages 2 years and older.

It comes in a ready-to-use vial, and you can self-inject it subcutaneously (just under your skin) every 2 weeks. If your HAE is well managed for more than 6 months, you may be able to change your medication schedule to once every 4 weeks.

In clinical trials, Takhzyro reduced the number of attacks requiring acute treatment more than a placebo did.

Berotralstat (Orladeyo)

Approved in 2020, Orladeyo works to prevent attacks in people ages 12 years and older. It’s a capsule you take once per day with food. In clinical trials, people who took this drug had significantly fewer attacks than those who took a placebo.

Ecallantide (Kalbitor)

In 2009, Kalbitor became the first kallikrein inhibitor to gain approval in the United States. This drug is used to treat acute attacks in people ages 12 years and older. Due to the risk of anaphylaxis, a healthcare professional needs to give you a dose of this drug. In some cases, you may need a second dose.

In clinical trials, 50% of participants who received Kalbitor reported significant symptom improvements for at least 45 minutes within 4 hours of taking the drug, while only 33% of those who received a placebo did.

C1 esterase inhibitors can stand in for missing or inadequately functioning C1 esterase inhibitors in your body to manage bradykinin levels. According to a 2019 research review, C1 esterase inhibitors are effective for both preventing and relieving acute attacks.

Cinryze

In 2008, Cinryze became the first drug to be approved for the prevention of HAE attacks. Derived from human plasma, this injectable medication is for adults and children ages 6 years and older.

It comes as a freeze-dried powder that you mix with sterile water. Once you receive training on how to prepare and inject it safely, you can self-inject the medication into a superficial vein every 3 or 4 days.

Haegarda

Haegarda was approved in 2017 for the prevention of HAE attacks in people ages 6 years and older. Also derived from human plasma, this drug comes as a single-dose vial of freeze-dried powder that you mix with sterile water. With training, you can self-inject it every 3 or 4 days.

Ruconest

Ruconest was approved in 2014 to treat acute attacks in adults and adolescents with HAE. This plasma-free recombinant C1-inhibitor is available in a single-use vial that you mix with sterile water. After training, you can self-inject this medication into a vein.

Berinert

The FDA approved Berinert in 2016 for the treatment of acute HAE attacks — specifically for symptoms affecting the abdomen, face, and voice box — in adults and children. This plasma-derived C1 esterase inhibitor was the first treatment approved for use in children. It comes as a freeze-dried powder that you mix with sterile water. With training, you can self-inject it.

Bradykinin antagonists block the effects of bradykinin, a peptide that makes your blood vessels dilate and causes swelling.

Icatibant

Icatibant was approved in 2011 for the treatment of acute attacks in people ages 18 years and older. It comes as a single-dose prefilled syringe that you can inject just under your skin. It’s available as a generic or under the brand name Firazyr.

In three clinical trials, icatibant reduced baseline symptoms by 50% in a median time of 2 to 2.3 hours.

There are a number of promising new therapies on the horizon, including:

  • Donidalorsen: This is a subcutaneous injection that reduces pre-kallikrein expression. In phase 3 clinical trials, it reduced the frequency and severity of attacks.
  • Sebetralstat: This on-demand oral therapy reduced the severity of attacks more quickly than a placebo in clinical trials.
  • Garadacimab: This is a monoclonal antibody given by injection once per month to prevent attacks in adolescents and adults. In clinical trials, it significantly reduced attacks.
  • NTLA-2002: This is gene editing therapy designed to lower kallikrein levels. Studies have found that this therapy may reduce kallikrein levels and the number of attacks per month.

Though these treatments are promising, researchers are still studying the potential benefits and risks of these and other therapies.

Several therapies are now available to help prevent HAE attacks. In addition, there are newer on-demand medications to tackle acute attacks and improve overall quality of life. Your healthcare team can help you understand the pros and cons of these therapies and how they may fit into your treatment plan.