Learnings for the global community

It can be helpful to establish a partnership with HAE specialists for access to HAE medication. Advocacy organizations can help provide data and knowledge about living with HAE, which can help healthcare professionals and people with HAE to make strong arguments to secure funding or reimbursement.

You can read our summary of the discussion in the scientific sessions here.

Friday afternoon – The main room takes centre stage

After lunch, all eyes turned to the giant ballroom that housed the general conference sessions. As the 1,400 representatives of the US HAE Community took their seats, they were welcomed by Tony Castaldo, HAEA CEO and Chairman of the Board, along with HAEA President and Board Member, Henrik Balle Boysen.

Tony and Henrik began by reinforcing the theme of the conference, Embracing A Brighter Future. The theme demonstrates how far the community has come and how much more opportunity there is ahead to improve the lives of people with HAE. “What is important in the future,” Tony said, “is engagement with as many people as possible, to show the value of being part of an organization that can strongly advocate for their needs.”

Tony showcased the range of HAEA’s highly successful programs and how HAEA’s support has helped individuals with medication challenges. You can read more about the exceptional work of the HAEA in their latest Annual Report, available for 2024.

Henrik reminded people that there are still challenges to be faced as a community. He and Tony used the phrase ‘ Protect What Matters’ to rally the conference delegates to be ready. There have been increasing issues with denials and delays. While problems with Medicare have been addressed, they demonstrate the need to avoid complacency. Tony also mentioned the need to participate in research and trials, as there can be no guarantees that future rounds of treatment approvals will be as positive. In conclusion, the two HAEA leaders reminded the participants of the innovation and creativity present in the HAE community and how the HAEA’s history showed what can be achieved when everyone works together.

What’s next for HAE – What you need to know

Dr Marc Riedl came up to the stage to discuss what he felt were some hot topics in HAE, broadly categorized into diagnosis and management. Starting with diagnosis, Dr Riedl told the audience how refreshing it is to hear that HAE patients have educated their family doctor or a doctor in the emergency room. This is something he encouraged everyone to do (if you can).

Recognising the work of both the HAEA and HAEi, Dr Riedl said that diagnosis is a lifesaver. For Type-1 and Type-2 HAE, there are good tests. With HAE-nl-C1INH it is more difficult. There are 6-8 genes that are identified as causing HAE-nl-C1INH, but not everyone with the condition has one of these. One solution is to look at the system in the body that goes wrong in people affected by a form of HAE. This can happen at the very top of a cascade of biochemical reactions, at the bottom, or somewhere in between. To help with this, Dr Riedl referenced the work of Drs Zuraw, Bork, and Maurer in developing a standardized way to try to reach a diagnosis of HAE-nl-C1INH.

Moving onto management, Dr Riedl noted that HAE Type-1 and Type-2 were only really discovered around 60 years ago, and progress in this time has been remarkable. In the last month alone in the US, there have been two new medicines. There are oral therapies. There are biological medicines that may only need to be given two or four times a year. There are RNA-targeted therapies, and then there’s the possibility of editing out the faulty gene causing the HAE.

It may seem, Dr Riedl admitted, that there might not be a need for so many options. The need is there because there is so much variability among individuals. What will work for one won’t necessarily work for others.

Moving on to the importance of clinical research, Dr Riedl reminded people that advances in care come because people with HAE share their experiences. This way, we know about how the condition affects quality of life. He encouraged people present to take part in surveys and trials, and ‘use it as an opportunity to get better for yourself, and for your community.’

In closing, Dr Riedl told the audience about how hard everyone is working to make HAE as small a thing in people’s lives as possible. He wanted people to know it’s there, but that it doesn’t interfere with life.

Protecting access to HAE therapies

The importance of this topic to people with HAE in the US was reinforced by the time dedicated to this subject: this was one of three sessions across the two days of the Summit.

Although highly specific to the US healthcare system, some of the discussions are relevant to anyone, anywhere, who may be struggling to access effective HAE medication. Here are the top tips from the panel:

• Communication is one of the most important things. Everyone needs to talk. The patient and the doctor can make a formidable team in challenging decisions.
• Every patient should understand the power of their personal story. Be prepared to say clearly how vital medication is and how HAE affects your life. Only the person with HAE can do this.
• Understand that there are (almost) always opportunities to appeal. Never take no for an answer. Talk to your doctor. Work with your HAE organization. Reach out to HAEi. You are never alone.

HAEA-initiated research programs

Next on stage were HAEA Research Advisor Deborah Corcoran, along with Christine Selva, HAEi’s Senior Director for Health and Research, and CEO and Chairman Tony Castaldo.

Ms Corcoran, a self-proclaimed data obsessive, opened the discussion by asking about HAEA’s advocacy research and why it’s vital.

Tony responded that insurers, and those who make the decisions about access to and reimbursement of medicines, will only consider paying for medicines when presented with real-world evidence demonstrating the horrific burden of HAE and the life-changing benefits brought by modern medicines. This is different from the clinical research that pharmaceutical companies undertake. HAEA research, which is similar in outlook to that done by the HAEi, generates data on how the disease and its treatment impact the everyday lives of patients.

The following research programs, either ongoing or concluded, were discussed:

• Work to understand the value of treatments for HAE beyond cost
• The impact on patients when payors deny or delay access to treatment
• A new US-validated tool to specifically measure how HAE affects quality of life
• A shared-decision-making tool
• An expert consensus update of our understanding of HAE-nl-C1INH and how it is treated. For the first time, this makes clear that treatment is critical following a diagnosis, even in the absence of a known genetic mutation or biomarker.
• Estimates of the prevalence of HAE in the US
• The impact of HAE on the lives of caregivers and on pediatric patients
• A snapshot of the current well-being of the entire US HAE community, led by the HAE Medical Advisory Board
• A study to understand how HAE changes for people over a 12-month period

The clinical papers published as a result of the HAEA research are all available for free online. All those on stage encouraged people to read and share the information, and thanked them for their participation in the research projects. ‘We simply cannot do this work without you,’ Tony concluded.

HAEA – Driven by impact

A hugely impactful personal story was given by youth advocate Noah Davis. He spoke eloquently and powerfully about the impact of advocacy on his life. He focused the audience on two things that he had learned to date:

• People care. There are always individuals and groups out there that will help you and support you. You are never alone.
• There is power in your story and your voice. He told the audience that they have the power to change the world.

Ask the Experts Q&A

The final session on Friday was the first of two expert Q&As spread across the Summit. In the first, Dr Bruce Zuraw moderated a panel consisting of Dr Sandra Christiansen, Dr Henry Li, Dr William Lumry, and Dr Timothy Craig. The questions were many and varied, and we present a selection here.

I’m expecting my first child. When’s the earliest I can get the baby tested?
It is possible to test the baby still in the womb, either through a tissue sample or from blood in the placenta.

Since going through the menopause, I’ve had fewer HAE attacks. Will this continue?
The course of HAE is never entirely constant. For some, it will get better, for others, it will get worse, and for some, there will be no change. What happens to one person, such as the drop in hormones after the menopause, does not mean there will be no more attacks.

What is the impact of changes in diet on HAE?
Doctors don’t have the answer to this. For some people, changes in their diet can impact their well-being and the severity of their disease, but this will be completely individual. There is no evidence to suggest any benefit, right now.

Are there any long-term side effects for children on HAE prophylaxis?
The doctors felt it reasonable to assume specific medications for HAE are safe, as there is nothing to suggest any long-term side effects. The doctors were keen to stress that long-term use of androgens (steroids) is highly likely to have significant long-term side effects, especially on young children.

Should family members without symptoms get tested?
Yes, the doctors said. If you have an attack, anywhere in the world, and you don’t have treatment because you are not diagnosed, you are at risk.

Does your overall health affect the severity or frequency of attacks?
As with the question about diet, none of the doctors was aware of any data to confirm if overall health and fitness had any impact. Dr Christiansen suggested that doing all the things which help health, such as getting plenty of exercise, eating a good diet, and avoiding bad things, may minimize the impact of any health condition.

Youthful antics

As the Summit came to the end of its first day, Global Perspectives got a peek at what was going on in the Youth Track. The HAEA team was expecting over 200 young people in both the Brady Club (for children aged 4-12) and Youth (13-25 year olds). Dedicated professionals from The Painted Turtle took care of the Brady Club, with workshops, films, and games. The Youth group likewise had fun, learned from each other, and from healthcare professionals.

Saturday

It was another early start on the Saturday, with a packed agenda. Some of the session topics were dedicated to sharing knowledge that we’ve covered in our Professional-Scientific Track snapshot (such as HAE-nl-C1INH and pediatric research), so this is a selection of the other topics discussed.

HAEA grassroots advocacy network

In the US, the HAEA maintains a powerful network of people with HAE who are committed to engaging with their elected representatives to advocate for the needs of people with the condition.

Jess Myers, HAEA’s Advocacy and Communications Manager, was joined on stage by a specialist in lobbying policymakers, Dane Christiansen.

Jess told the audience that it is essential to overcome any sense of ‘imposter syndrome’. Everyone has the power to be an advocate for HAE. Telling someone about HAE is advocacy. You don’t have to speak to a politician. Just being happy to communicate about your condition to anyone outside the community is advocacy.

Jess outlined some of the HAEA programs underway in the Grassroots Advocacy Network. There is training for people, and pre-prepared templates which can be sent to elected representatives asking for their support. There are also regular updates on important potential new laws that people with HAE should know about.

Learnings for the global community

Keeping an eye on what’s going on in your country can help to pre-empt any challenges or opportunities. Developing basic template letters can encourage people to lobby their local politicians effectively.

While Dane Christiansen’s presentation was inevitably focused on the situation in the US, his advice to anyone about advocacy was universal. He encouraged people to think: ‘Policy not politics’. He said that HAE and its care are not about partisan politics or politicians arguing. It is about advocating for what the community needs, regardless of the political persuasion of any individual.

Words from HAE International

Fiona Wardman, HAEi Executive Vice President and Chief Advocacy Officer, and Jørn Schultz-Boysen, HAEi Executive Vice President and Chief Operating Officer, represented HAEi in Baltimore. Their presentation outlined the mission of the HAEi, to ensure that every person with HAE, no matter where they live, can access an accurate diagnosis and life-saving HAE therapies. Key to this was the support programs and tools on offer.

HAE TrackR was discussed, along with the HAE Companion app and its emergency cards in many global languages. All HAEi resources are free to download and use. HAEi LEAP, a program of training for youth advocates, has included several young people from HAEA, and ACARE is available to ensure people with HAE can access centers offering the best treatment for the condition.

The forthcoming 2025 HAEi Regional Conference EMEA was mentioned, and on behalf of HAEi, Jørn was happy to announce that the 2026 HAEi Regional Conference Americas will take place in Ottawa, Canada.

In conclusion, Fiona and Jørn encouraged all people with HAE to work together, nationally and internationally, as this will deliver the best benefits for everyone, no matter where they live.

Ask the experts Q&A – Part II

The popularity of the expert Q&A was such that a second session was placed in the diary. This time the panel was moderated by Dr Marc Riedl, who was joined on stage by Dr Aleena Banerji, Dr Paula Busse, and Dr Mark Davis-Lorton.

With over 70 questions to answer, Global Perspectives offers highlights of the session:

Will laboratory tests show normal C1 inhibitor levels if a patient is on prophylaxis?
Not necessarily. The doctors didn’t feel that any such tests would be of much use. There is natural variation in all people, so changes wouldn’t suggest anything.

Can people with HAE take the latest medications for weight loss?
The doctors knew of no reason why HAE patients could not use these treatments.

What are some prodromal symptoms other than rash?
There is some evidence of numbness or tingling, or even just a general feeling of being unwell.

Are there studies of geriatric HAE patients?
Some of the trials of HAE have included older patients, but there’s limited data. The more patients take part in national Registries, the more information will be available on topics like this.

What work is underway on gene therapies, and what are the expectations in the coming years?
Studies are ongoing, but as yet we are waiting for more data before we can make predictions. The goal is to be curative or at least attack-free in everyday life.

If a person is pregnant with a diagnosis of HAE with normal C1 Inhibitor, what’s the likelihood of passing this to children?
The genetic mutation is dominant, which means there is a 50% chance of a child having the condition if one parent has HAE. If both parents have HAE, then there is a 75% chance that the child will also have HAE.

Does HAE affect the ability of the body to regulate glucose or manage insulin?
The doctors were clear and concise: No.

Is losartan an acceptable medicine for someone with HAE?
The big concern for HAE and heart medication is ACE inhibitors. Losartan is not one of this class of medicine. There are rare cases of angioedema from the class losartan belongs to, but they are not contraindicated in people with HAE.

The final question was: Why does having multiple kids make HAE worse?
Lightheartedly, the medical panel felt that it was down to the additional stress of raising children!

Dr Riedl brought the session to a close and turned the stage over to Tony Castaldo and Henrik Balle Boysen to close the Summit.

Making Brady bears

Tony told the audience that some of the HAEA young people had been stuffing teddy bears throughout the Summit. These bears will be sent to newly diagnosed young people, so they know from the first moment that they are not alone. That bear is a symbol of a fellow patient and the care they show.

1: From SERPING1 to multiple genes: Genetics and the mechanisms of swelling in HAE

One of the world’s leading experts on HAE genetics, Dr Allen Kaplan, explained to the assembled healthcare professionals that there is now a growing body of knowledge about the genetic mutations at the heart of HAE. He demonstrated that even with normal C1 inhibitor present, it is possible to have angioedema by overwhelming the body’s systems with bradykinin.

2: The current state of the art for HAE biomarkers

Dr Huamin Henry Li discussed the ongoing work to identify biomarkers in HAE. The importance of biomarkers, he said, was threefold. Firstly, they provide an essential means of diagnosing HAE properly, which is increasingly important to distinguish between various HAE types, and to individualize treatment. Secondly, biomarkers offer a way to measure the effectiveness of a therapy, even in the absence of HAE attacks, as the underlying levels can indicate how well a treatment is working in an individual, with the opportunity to personalize treatment. Finally, they help to make clinical trials more effective by providing clear ways in which to measure the performance of a potential new medicine. Dr Li also showed the latest work on measuring bradykinin, which may be beneficial to the management of HAE.

3: Perspectives on HAE-nl-C1INH from a recently published landmark review

The first of the panel sessions was dedicated to discussing the latest work in diagnosing and treating HAE with normal C1-inhibitor (HAE-nl-C1INH). The panel of Dr Bruce Zuraw, Dr Marc Riedl, Dr Sandra Christiansen, and Dr Aleena Banerji all presented on a different aspect of the condition.

Opening the session, Chair of the Scientific Committee, Dr Zuraw, presented a potential HAE case of a mother of two with recurrent angioedema but no diagnosis. Depending on how key questions are answered, the diagnosis and treatment received could radically change. Dr. Zuraw reinforced the importance of asking the right questions and doing the right tests.

Dr Banerji spoke about the history of HAE-nl-C1INH. She reminded the audience that, as a disease, it had only been identified in 2000. She said there was a lack of knowledge about the prevalence of this form of HAE, but it is certainly rarer than HAE Type-1 and HAE Type-2. She also suggested that HAE-nl-C1INH can be very varied from person to person, potentially leading to underdiagnosis or misdiagnosis.

Returning to the genetics of HAE, Dr Riedl praised the ongoing work to understand the genetics of HAE-nl-C1INH better, as this allows for testing and eventual diagnosis. He expressed caution about the value of family history of angioedema, as some people may not know their family, or symptoms might simply not have been discussed. Several studies of US doctors treating HAE indicated that there is a lot of variability in the approaches used to diagnose and treat people with HAE-nl-C1INH.

Dr Zuraw showcased a new diagnostic and treatment algorithm for HAE-nl-C1INH. Using a step-by-step approach, the algorithm starts by excluding common diagnoses such as ACE-inhibitor medications leading to angioedema, or HAE due to C1-inhibitor deficiency, before progressing to tests and treatments for HAE-nl-C1INH.

Finally, Dr Christiansen spoke on treatment. She told the audience that the patients coming to see her don’t expect a miracle, but they do expect better. Dr Christiansen presented data from a survey of physicians treating HAE-nl-C1INH, exploring which medications, in their experience, had seen success in treating HAE-nl-C1INH. The survey indicated the icatibant and on-demand plasma-derived C1 inhibitor offered benefit in treating attacks. Lanadelumab was used in some cases, as was berotralstat, both of which seemed to demonstrate some efficacy. Anabolic steroids were not used, but tranexamic acid looked to have a benefit regardless of the genetic variant of HAE-nl-C1INH.

Questions to the panel related to concerns about the cost and availability of genetic testing, and how to manage patients with HAE-nl-C1INH who may need surgery or during childbirth. Additionally, there was a discussion of the potential value of prodromes in HAE. The panel expressed scepticism that these could be effectively used to diagnose different forms of the disease.

4: Considerations for the pediatric population with HAE

The second panel discussion was composed of Dr Andrew MacGinnitie, Dr Timothy Craig, and Dr Michael Manning. The group focused on the care of children and adolescents with HAE, and the panel was asked a series of questions.

Dr Craig was asked about the timing of HAE testing in newborn babies. He recommended that this take place in the first month of life. With genetic testing, this can be a challenge, unless the mutation is already known in the parents. There is some reluctance to test for HAE from some parents and families, the panel conceded. But this is best addressed through education on the importance of a diagnosis. The panel was also asked about testing when there is no family history. The impact of puberty and the associated hormonal changes was the topic of another question, and the panel felt that this can be hugely variable, with some patients worsening while others seeing no change. The desire to address the hormones with birth control is understandable, but not the right solution, they said. A common question was asked about sports and activities in children with HAE. One of the panel members recounted that a patient was able to compete internationally in wrestling, so it is important to work with patients to allow them to achieve their goals.

The panel also rated the value of young people being part of advocacy groups such as the HAEA, where they can see other people in the same situation and not feel isolated by their condition.

5: Access to HAE treatment: Prior authorizations and eligibility

An eagerly awaited session was around the health systems in place in the US, especially ‘prior authorizations’, where doctors have to get approval from health insurers before a medication can be prescribed. This is done to control costs, but can lead to US patients struggling to access medication, or losing the access that they previously had.

On stage was Troyce Venturella from the HAEA, who works with patients and physicians to address issues around medication access. She was joined by a pharmacist who works in the insurance industry, Steven Kheloussi, who, it was said, lightheartedly, would be ‘taking the tomatoes’ as the panel may be hostile to the health insurance industry. Also on stage were HAE experts Dr William Lumry and Kimberly Poarch to give their perspective.

The panel explained the landscape of health insurers and how prior authorizations are being used. There were examples of how problems had been overcome, and Mr Kheloussi was able to give context and advice on how best to approach the process. In particular, he highlighted the importance of providing the requested information very concisely. He felt that a complete medical history running to many pages is counter-productive as it means more time is spent having to review, when a succinct response would be better.

6: Update on emerging HAE therapies and current clinical trials

The final presentations and discussions were around the latest advances in treatment. Speaking first was Dr Christine Radojicic, who discussed advances in oral medicines. She started with sebetralstat, which was extremely recently approved in the US under the brand name Ekterly. She summed up the efficacy data as favorable. She also discussed concerns about side effects in the stomach and digestion, as this is an oral on-demand treatment for HAE attacks. Dr Radojicic showed that there were very few gastrointestinal side effects reported in the trial. The use of the medicine in people with laryngeal attacks was also discussed. In the trial, every patient with a throat swelling was able to swallow the tablet. Moving on to an as-yet still unapproved medicine, deucrictibant, Dr Radojicic confirmed that this medicine is being considered for both on-demand and prophylaxis. Evidence to date is promising.

Dr Joshua Jacobs was next to speak. His talk focused on the emerging biological therapies, which make use of living cells to treat and prevent HAE. These included garadacimab, which showed an average of 95% reduction in HAE attacks in a trial, and navenibart, which could be given every three or six months to prevent attacks. Dr Jacobs indicated that this looked like an effective agent based on the trials to date.

The potential gene therapy was also discussed, including the way it works by clipping out the mutated gene causing HAE, replacing it with an effective one.

Finally, Dr Marc Riedl gave a presentation on potential HAE treatments that harness RNA, which people may remember was used to develop COVID vaccines. Three potential treatments were mentioned: donidalorsen, ADX324, and a third for which little is currently known. These medicines work by interfering with the production of a protein that causes HAE attacks by silencing a mutated gene. For donidalorsen and ADX324, Dr Riedl suggested that the data in trials to date have shown some steep declines in mean attack rates.

Summary

In summary, Dr Zuraw returned to the stage. He thanked all presenters and the audience and asked his fellow health professionals to remember that the United States is in a privileged position when it comes to treating HAE. Most of the rest of the world faces greater issues. Finally, he drew attention to the vital role of patient advocacy in delivering the ‘abundance of riches’ in terms of treatments for people with HAE.

From the Poster Room

After the Professional-Scientific track, attention turned to over 30 scientific posters. Here we highlight posters related to living with HAE; its impact on mental health; what patients want to see from their HAE treatment; and the challenges of recruiting people into clinical trials.

Patient perspectives on the importance of HAE treatments
Kimberly Poarch and colleagues wanted to understand how people with HAE perceived treatment, especially around oral therapies. They found that individuals with HAE see both on-demand and long-term prophylaxis as important aspects of treatment. The majority of study participants were not willing to stop taking long-term prophylaxis, even if oral on-demand treatments exist, because they preferred to avoid attacks altogether or were concerned about more frequent or severe attacks. However, the idea of an oral medication was of interest.

Recruitment challenges for rare disease clinical trials: A systematic review
The authors, led by Mindy Demarco, wanted to identify the challenges of recruiting for rare disease clinical trials and explore effective strategies to secure patient participation in clinical studies. The authors concluded that recruitment for clinical trials in rare diseases can be challenging because diagnoses can be complex, and patients are geographically spread. They suggest that addressing structural barriers, such as speeding up diagnosis, and tailoring communications about the trials to suit specific groups of patients, may help lead to better engagement with patients.

Treatment burden remains in HAE, despite goals to reach ‘normalization’
The authors of this research, which included Dr Paula Busse as lead author, presented survey data on perceptions of HAE control and the concept of normalization, as well as the emotions associated with HAE and its management. The conclusions reached included:

• Most respondents reported multiple attacks in the last year, and thought about HAE weekly, despite considering themselves to be well-controlled
• Lots of reported concerns about the need for lifetime medication use, which meant it was difficult to feel like they lived a ‘normal’ life
• HAE attacks were associated with negative emotions. The idea of being attack-free was associated with positive emotions, particularly when it was achieved without the need for ongoing medication use

Hereditary angioedema (HAE) and post traumatic stress disorder (PTSD)
Dr Sandra Christiansen and colleagues presented a study of people with HAE that investigated how their mental health may be negatively impacted by attacks, risk of not being able to breathe during a throat attack, and the loss of a loved one to HAE. The study asked people questions to identify if they may have post-traumatic stress disorder (PTSD). In conclusion, the authors were able to identify a high prevalence of potential PTSD in people with HAE. People with increased disease burden, higher rates of depression, and lower quality of life were more likely to be considered to have PTSD. Speaking later, Dr Christiansen indicated that the rates of potential PTSD seen in these HAE patients were profound, perhaps being even higher than that seen in military veterans exposed to combat.

Living with HAE with normal C1-inhibitor: The worry of when
Kirstie Cline and colleagues presented a visually exciting poster. They found that improved resources are needed to help healthcare professionals communicate about pain and how attacks resolve over time. They also suggest that people with HAE may need mental health support to manage anxiety around HAE attacks.