Sebetralstat, mRNA, Ekterly, donidalorsen, gene-editing, Dawnzera, garadacimab, anti-sense, oligonucleotides, Andembry. The HAE community heard many new words in 2025, which turned out to be quite the year for HAE treatment. Three new medications were approved, and exciting data from clinical trials pointed to further advances in 2026. But why should you be interested in more treatments, and what could these innovations mean for people with HAE, including those who currently have few treatment options? Global Perspectives takes a look behind the headlines and speaks to advocates and medical experts about what might be next.

It is important to stress that existing treatments are effective for many HAE patients. Not all new medicines are currently licensed or reimbursed in every country. Importantly, no one should stop or change treatment without discussing the matter in detail with their healthcare professional.

In some countries, people with HAE can now choose among a wide range of options for treating and preventing attacks. This progress is striking when you consider that many rare diseases still have no approved treatments. Tony Castaldo, HAEi CEO and Chairman of the Board, who has HAE and is a vocal advocate for access to all approved HAE medicines, says: “The global HAE community should be very proud of the progress made to date. Pharmaceutical companies invest in HAE because we are an organized and motivated group that enthusiastically participates in clinical trials. What’s more, we know how to approach policymakers and provide testimonial and documentary evidence showing the importance of granting access to HAE medicines.” He adds: “HAE symptoms and how they affect us are highly individual, and that is why it’s important to have a variety of treatment options.”

Healthcare professionals agree that having multiple treatment options is vitally important. Dr Marc Riedl, Clinical Director of the US HAEA Angioedema Center at the University of California, San Diego, tells Global Perspectives: “The existing modern treatments for HAE have significantly improved our ability to manage HAE, but not every medication works equally well for every individual, and side effects vary from person to person. More options increase the chances of optimizing treatment for each person.” Dr Ankur Jindal, Senior Consultant, Pediatric Clinical Immunology and Rheumatology, Manipal Hospitals (Old Airport Road), Bengaluru, India, comments: “Newer treatment options are welcome because people continue to have acute episodes.” Dr Riedl and Dr Jindal also stress that HAE is a disease that currently requires lifelong treatment. That’s why pharma companies are investigating and offering alternatives that can be taken less frequently or via other routes of administration, such as orally.

What’s new and what’s next?

The clinical experts spoken to by Global Perspectives noted that new and emerging HAE therapies build upon many years of basic science that uncovered the central drivers of swelling attacks—namely the kallikrein-kinin pathway and the peptide bradykinin.

As mentioned earlier, 2025 saw major regulatory approvals for three new HAE therapies:

• Sebetralstat (Ekterly) is the first—and, as yet, only—oral, on-demand HAE treatment. It treats attacks by blocking plasma kallikrein, thereby reducing bradykinin production.
• Garadacimab (Andembry) is a once-monthly injection under the skin that stops the activation of Factor XIIa, which is the biological trigger that essentially kicks off the kallikrein-kinin pathway that leads to HAE attacks.
• Donidalorsen (Dawnzera) reduces kallikrein levels by blocking the specific messenger RNA responsible for its production in the liver. It is called a targeted antisense oligonucleotide (ASO) therapy and is delivered through an injection under the skin. The treatment can be given at either 4- or 8-week intervals.

Looking to medicines of the future, deucrictibant blocks the hormone bradykinin from binding to receptors and is being studied for both on-demand and prophylactic use. The on-demand phase 3 trial has been completed, and an application for regulatory approval is planned for submission in the first half of 2026. A phase 3 prophylaxis trial is ongoing.

Therapies are also being developed using gene editing and small interfering RNA (siRNA) technologies. A phase 3 clinical trial is underway that uses CRISPR-Cas9 tools to ‘knock out’ the prekallikrein gene, aiming for long-lasting attack prevention after a single treatment. Clinical trials are also underway with two companies testing siRNA to reduce prekallikrein by targeting its messenger RNA—the genetic “instructions” cells use to make proteins. So far, the early phase trial data is encouraging for all of these medicines, however, nothing is certain until pivotal trial results are reported.

2026 is also shaping up to be a breakthrough year for treatment for children with HAE. In mid-December 2025, an oral pellet form of the existing medicine berotralstat (Orladeyo) was approved in the US for the prevention of HAE attacks in children aged two to less than 12 years. Additional pediatric approvals and expanded indications for other HAE therapies are likely.

Your HAE community needs you

Advances like these depend on clinical research and patient participation. People with HAE can encourage further investment in the treatments of tomorrow by continuing to participate in:

• Clinical trials for new therapies or additional indications for those currently available
• Clinical registries
• Genetic studies
• Patient experience research

We have come so far, and have further to go. It’s important never to forget that every bit of knowledge gained regarding the underlying science of HAE adds to a cumulative understanding that could revolutionize future HAE treatments. You can learn about trials currently recruiting by asking your HAE doctor, speaking with your Member Organization, or checking out our Clinical Trials section. Your healthcare team can help you determine whether you are eligible to enroll in a clinical trial.

Dr Jindal noted the stark shift in HAE care: today’s highly effective on-demand and preventive options contrast sharply with the past, when treatment often focused on keeping people alive. Despite this progress, much work remains. For Dr Jindal, treating patients in resource-constrained settings such as parts of South East Asia, Africa, and South America remains an everyday challenge, with access to first-line HAE therapies still limited or absent. As a result, he says, patients in these regions continue to experience a significantly impaired quality of life and, in some cases, avoidable mortality related to HAE.

Dr Jindal has seen improvements over the past 5–10 years: “Awareness of HAE among healthcare professionals has improved substantially, leading to higher diagnostic rates. In many resource-constrained countries, the situation has evolved from virtually no discussion of HAE and almost no diagnosed patients, to one where a growing number of individuals are correctly diagnosed and followed. Diagnostic facilities have improved, access to on-demand treatment has become available in a few countries, and there is now visible growth in physician networks, patient support groups, and engagement from the pharmaceutical industry.”

Helping close the access GAP

Guided by our vision to overcome barriers and bring effective treatments everywhere, HAEi is dedicated to helping Member Organizations secure access to modern HAE medicines. One relevant program is our HAEi Global Access Program (GAP), which enables patients to receive HAE-specific therapies in countries where these treatments are not yet commercially available and where establishing traditional distribution channels is especially difficult. GAP’s success in South Africa demonstrated the model’s viability, and we continue to engage with multiple pharmaceutical partners who may be interested in using GAP to broaden access to their medicines.

In parallel, some governments have begun to recognize HAE within broader rare-disease frameworks, including the introduction of rare-disease policies in selected countries. Dr Jindal says: “Together, these developments represent a meaningful and hopeful shift, offering a more optimistic outlook for patients with HAE in resource-constrained settings. Dr Riedl echoes this view: “Medication access is an incredibly important challenge that we must work to solve. The remarkable scientific advances and clinical development efforts in HAE mean little if medications don’t reach the people who need them. My hope is that with the increasing number of HAE therapies, there will be greater opportunities to get modern therapies to more regions and people.”

More medicines, more access?

Looking ahead, while the latest science and medicines may seem far away in countries with little or no access to HAE-specific medication, these new launches may provide an opportunity. The introduction of additional medicines could result in pricing competition, making existing HAE therapies more affordable and potentially placing them within the budgets of health care decision-makers in countries where access is currently limited due to cost. According to Dr Riedl, this will require: “Educational and advocacy efforts to ensure decision-makers in health care systems understand the critical importance and value of these effective treatments to individuals and families affected by HAE.”

HAEi, a powerful partner for HAE advocacy in resource-constrained countries

From its inception, HAEi has existed to provide tools, resources, educational programs, and hands-on assistance to empower awareness, accelerate diagnosis, and champion access to life-saving HAE therapies. This means that whenever and wherever—from Bogota and Brussels to Botswana and Bahrain—HAEi is present. The network of HAEi Regional Patient Advocates and Advocacy Leads work every day, collaborating with local advocates to gain access to, and reimbursement for, HAE medication. On regular occasions, such as recently in Nepal, this has meant HAEi is part of face-to-face meetings with health ministry officials. Additionally, HAEi Advocacy Academy supports everyone in becoming a better advocate for themselves and their community. HAEi’s regular regional and global conferences bring together advocates to learn and share knowledge in pursuit of access to life-saving and life-giving HAE therapies.

In addition, HAEi offers patient-driven research protocols that generate real-world data on the economic and social benefits of treatment. This work provides Member Organization advocates with an opportunity to present an evidence-based patient perspective to health care decision makers. Finally, our country-specific and regional guideline initiatives help lay the groundwork for winning access by supporting expert HAE physicians and patient leaders to develop evidence-based guidance in Malaysia, Pakistan, and the Asia Pacific.

Building the case for access to the treatments of tomorrow

The landscape of HAE management has changed remarkably over the past decade. There are now more treatment options than ever before, including well-tolerated therapies for long-term prophylaxis.

The vital importance of HAE advocacy in every successful effort to gain access to medication is clear, and Dr Riedl emphasizes the importance of collaboration when he says, “Given the complexity and variability in health care systems, it is essential that healthcare authorities, regulators, industry, healthcare professionals, and HAE advocates forge meaningful collaborative relationships. We must work through these challenges together as a global community, and HAEi continues to lead the way.”

2025 was an inspiring year for HAE treatment, and 2026 is shaping up to be similar. Dr Riedl captures a spirit of optimism when he says, “It’s certainly an exciting time to be working in the field of HAE, and more importantly, I hope an encouraging time for people living with HAE. About 15 years ago, we saw an initial ‘wave’ of modern therapies for HAE, which substantially changed our approach and recommendations for HAE management. In my view, we’re now in the midst of another ‘wave’ of novel treatments, with the potential to further improve HAE care. The prospect of having more options to improve access and individualize treatment plans makes me very optimistic for the future.”