New hope for rare disorder

July 26, 2018, Goethe University Frankfurt am Main
Hand swelling caused by hereditary angioedema. Credit: Emel Aygören-Pürsün

Hereditary angioedema is a chronic disorder that can sometimes be life-threatening. Now, a new drug therapy has been successfully tested in an international study headed by the University Hospital Frankfurt.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent painful swellings of the skin and mucous membranes. Without treatment, ' quality of life is noticeably compromised: Angioedema may not only be disfiguring; in the gastrointestinal tract it may lead to severe abdominal colic ad in the upper airways it can even be fatal if left untreated. The frequency of angioedema attacks is unpredictable and varies from patient to patient; swellings may occur up to several times a week. The disorder affects about one to two in a hundred thousand people.

A new drug has been developed to help prevent attacks of hereditary angioedema and at the same offer the patients a convenient administration. It has now been investigated in an international study performed at over 26 university facilities in Europe, Canada and Australia. The results were clear: the drug is highly effective with regard to attack prevention and improvement in quality of life while offering a convenient oral administration. Dr. Emel Aygören-Pürsün, specialist in internal medicine at the Division of Oncology, Hematology and Hemostaseology at the Department for Children and Adolescents of the University Hospital Frankfurt, served as the principle investigator of the study.

"Hereditary angioedema is a condition that may be associated with lifelong impairment. With this fundamentally new development, we may reduce HAE- attacks and consistently improve our patients' quality of life," explains Dr. Emel Aygören-Pürsün. The HAE competence centre at University Hospital Frankfurt is one of the leading institutions nationwide for patient care and the clinical development of therapies for hereditary angioedema. Professor Thomas Klingebiel, Director of the Department for Children and Adolescents, underlines the significance of the results: "Pioneering patient care and cutting-edge clinical research – these are what University Hospital Frankfurt stand for." The results of the study have now been published in the renowned New England Journal of Medicine.

Genetic disorder leads to uncontrolled swellings

For most cases of hereditary angioedema, the underlying cause is a congenital deficiency or dysfunction of what is known as C1-inhibitor. As a result of C1-inhibitor deficiency, plasma levels of bradykinin increase, a peptide which locally increases the permeability of the smallest blood vessels.

The central role of bradykinin in the development of angioedema attacks is well established for hereditary angioedema. Attacks of angioedema in patients with hereditary angioedema are related to the action of bradykinin, whose generation is closely linked to another plasma protein, called kallikrein. If kallikrein is active, then bradyinin generation is the result. The inhibition of kallikrein should therefore be a suitable measure for prophylaxis of angioedema attacks.

Therapeutic breakthrough in the form of capsules

So far, the prevention of angioedema attacks in was bound to medication that required injections. Although drugs were also available as tablets, these proved either ineffective or were not licensed in many countries. In addition, some of them led to severe side effects and could not be administered to children or during pregnancy.

The new drug BCX7353 tested in the study is a synthetic small molecule that acts as a specific kallikrein inhibitor and is administered as capsules. The aim of the development was to achieve an effective prophylaxis with the distinct advantages of an oral administration yet without the side effects of the oral preparations used previously.

Study methodology

During the study, 77 patients were randomized to groups of four different dose levels or placebo. They took the respective dose once daily for 28 days. The patients noted in their diaries the frequency, localization and severity of the attacks; quality of life was recorded at the beginning and the end of the study using a validated questionnaire. Changes in the frequency of the attacks were investigated, as were the side effects from the treatment and the impact on patients' quality of life.

Convincing results

The results were positive: With a daily dose of 125 mg and higher, a significant reduction of angioedema attacks was demonstrated. Patients who took 125 mg of BCX7353 per day even experienced a reduction in the frequency of their attacks of almost 75 percent compared to placebo; over 40 percent of patients in that dose group remained completely free of attacks during the study. Also the increase in quality of life was most evident for the 125 mg dose; in addition, not only the number of peripheral attacks was reduced in this group but also those in the gastrointestinal tract. Moreover, the side effects of this dose ranged mild.

Overall, the study was able to clearly corroborate the efficacy of BCX7353 and at the same time provide information about the ideal dosage and tolerability of the new drug. Further studies will now be necessary to verify the efficacy and safety with its long-term administration.

Explore further: C1 inhibitor use reduces attacks in hereditary angioedema

More information: Emel Aygören-Pürsün et al. Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema, New England Journal of Medicine (2018). DOI: 10.1056/NEJMoa1716995

Related Stories

C1 inhibitor use reduces attacks in hereditary angioedema

March 23, 2017
(HealthDay)—Prophylactic use of the subcutaneous C1 inhibitor CSL830 is associated with a reduction in the frequency of acute attacks in patients with hereditary angioedema, according to a study published in the March 23 ...

A better way to treat ACE inhibitor angioedema in the ED

May 14, 2014
Investigators at the University of Cincinnati have found a safe and effective treatment for life-threatening angioedema attacks in the emergency department.

Angioedema induced by new classes of drugs

October 1, 2015
(HealthDay)—Two newer classes of drugs, dipeptidyl peptidase IV (DPP IV) and neprilysin inhibitors, can induce angioedema, according to research published in the October issue of Allergy.

In rare disorder, novel agent stops swelling before it starts

February 22, 2017
An early-stage clinical trial has found that, compared to a placebo, a novel medication significantly reduces potentially life-threatening episodes of swelling of the airway as well as the hands, feet, and abdomen of patients ...

Omalizumab effective for chronic spontaneous urticaria

March 31, 2016
(HealthDay)—Omalizumab is effective in patients with moderate-to-severe chronic spontaneous urticaria (CSU) symptoms and angioedema unresponsive to high doses of antihistamine treatment, according to a study published online ...

rhC1INH cuts attack frequency in hereditary angioedema

November 9, 2012
(HealthDay)—For patients with hereditary angioedema (HAE), weekly administration of recombinant C1INH (rhC1INH) is well tolerated and is associated with a reduction in attack frequency, according to a study published online ...

Recommended for you

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

New hope for cystic fibrosis

October 19, 2018
A new triple-combination drug treatment being trialled at the Mater Hospital in Brisbane could increase the life expectancy of patients with cystic fibrosis.

Bug guts shed light on Central America Chagas disease

October 18, 2018
In Central America, Chagas disease, or American trypanosomiasis, is spread by the "kissing bug" Triatoma dimidiata. By collecting DNA from the guts of these bugs, researchers reporting in PLOS Neglected Tropical Diseases ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Rapid genomic sequencing of Lassa virus in Nigeria enabled real-time response to 2018 outbreak

October 18, 2018
Mounting a collaborative, real-time response to a Lassa fever outbreak in early 2018, doctors and scientists in Nigeria teamed up with researchers at Broad Institute of MIT and Harvard and colleagues to rapidly sequence the ...

Researchers cure drug-resistant infections without antibiotics

October 17, 2018
Biochemists, microbiologists, drug discovery experts and infectious disease doctors have teamed up in a new study that shows antibiotics are not always necessary to cure sepsis in mice. Instead of killing causative bacteria ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.