HAE medications – current and new medicines

The penultimate of the 4 expert speakers on Saturday afternoon was Professor Philip Li, whom the audience first heard in Friday evening’s keynote. He introduced this talk as focused on medications. He acknowledged a very varied audience, with both experienced experts and people new to the disease, and the presentation would be broad.

Referencing Dr Longhurst’s presentation, Professor Li showed that many existing medications resolve leaky blood vessels caused by too much bradykinin. He told the audience, “The problem is that it’s tough to stop once it starts. It is why doctors tell patients they need to be treated early.” Professor Li explained that all the medications currently in development are trying to stop the whole process.

Medications for HAE come in 2 categories, Professor Li indicated. These are on-demand, given when a swelling occurs. The other is called preventative.

Before deciding what you should get, Professor Li counseled that you need to know what you shouldn’t. Many people with swelling get antihistamines, steroids, or adrenaline. These will not help at all with your HAE attack. He said that if you go to the emergency department, be alert if they don’t believe or understand your HAE.

Referring to the latest available guidelines from 2021, Professor Li indicated that the most straightforward way to treat is by replacing the C1-inhibitor in people with HAE, where they either don’t have enough C1 or the C1 they have doesn’t work correctly. C1-inhibitor is usually given as an infusion into a blood vessel. The good thing about C1-inhibitor replacement, according to Professor Li, is you are ‘nailing the problem.’ All patients can use C1-inhibitor, even children, pregnant women, and breastfeeding mothers.

Probably the most well-known HAE injection is the next treatment Professor Li described, icatibant. “It’s very good,” he said, “you can do it at home without a doctor, but pregnant women or those breastfeeding can’t use it.”

He briefly referenced a medicine limited to the US as an example of limited options for on-demand treatment.

Professor Li then moved on to the various ways you can use medicines to prevent swelling attacks from happening at all. For short-term prophylaxis, when an attack might be anticipated (such as after dental work), an infusion of C1-inhibitor can prevent an HAE attack.

Looking at long-term prophylaxis, preventing attacks over a long period, this field is growing, according to Professor Li. You can have regular infusions of C1-inhibitor or a special form of C1-inhibitor that absorbs slowly, giving more extended protection than twice-a-week infusions. A subcutaneous injection or a daily oral tablet is now used to prevent HAE attacks.

Professor Li moved the focus to look at how HAE treatment is changing. He acknowledged that some countries currently have nothing and stressed the importance of advocating for HAE-specific treatment.

He started by looking at his native Hong Kong. Here, he said, the approach was to secure treatment that prevented death. He wanted to save lives and relieve attacks. Now, he said, the focus is on gaining control. ‘Can I live a normal life?’ is now the question. Perceptions have changed. Patients and clinicians are considering the right medication for each patient and the treatment that best fits their lives. “For example, a patient might want the ability to treat attacks at home, or an injection might not be suitable,” he suggested.

He indicated that future medication could be summarized around 4 themes:

On-demand pill in a pocket
Sebetralstat and deucrictibant are the options being tested for this.

Prophylaxis with fewer injections
Garadacimab (every month), donidalorsen (every 2 months), and navenibart (every 3-6 months) are in clinical trials here.

Prophylaxis without injections
Deucrictibant is also being tested as a daily tablet preventative.

No more medication at all
Gene therapies that modify the faulty gene in people with HAE are being tested. Professor Li said it is very promising, especially for those who have tried multiple lines of therapy but are still having very severe attacks; however, it’s not going to be readily available everywhere.

Wrapping up his presentation, Professor Li admitted to being angry when they finally got C1-inhibitor therapy in Hong Kong. He could see in other countries that they were talking about the normalization of life, which should be everyone’s aspiration. He said that this is why it’s important to know what’s out there so you can see where we should all be aiming.

”It’s important that we all know what medications are out there and what’s coming, so we can see where we should all aim.”

Professor Li encouraged everyone to look at the current trials and join one if they could – to benefit themselves and develop future medication. He also asked the clinical experts to work together on a realistic consensus and advocate for the region, before closing with an invitation for the conference to come to Hong Kong.