Ruconest Works for 1 in 6 With Idiopathic Angioedema in Pilot Study

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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One person out of six treated with Ruconest (rhC1INH) for idiopathic non-histaminergic angioedema (InH-AAE) as part of an exploratory study showed a positive clinical response to the medication.

The findings may mean that Ruconest is effective in a subset of InH-AAE patients, the researchers noted.

The study, “Recombinant human C1 esterase inhibitor as prophylactic treatment in idiopathic non-histaminergic angioedema,” was published as a letter to the editor in Allergy.

Idiopathic angioedema is marked by chronic, recurrent swelling attacks that happen regularly without an identifiable cause. Patients who don’t respond to preventive treatment with antihistamines, a type of allergy medication, are considered to have InH-AAE.

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Ruconest, which is marketed by Pharming, is an approved treatment  for patients with hereditary angioedema. It’s a lab-made form of the human C1-esterase inhibitor, which acts to control the activity of C1, an important immune system protein. In hereditary angioedema, natural levels of the C1 inhibitor are insufficient, causing overproduction of a protein called bradykinin, which regulates blood pressure and inflammation.

Since patients with InH-AAE aren’t responsive to other types of allergy medications, a research team in the Netherlands investigated whether some cases of InH-AAE might also be mediated by bradykinin overproduction, thus making Ruconest a potentially promising treatment for them.

The team conducted an explorative Phase 2 study involving six InH-AAE patients at their clinic. All were observed for four weeks then treated for eight weeks with Ruconest, which was administered as an into-the-vein infusion twice per week. A second four-week observation period followed.

While five showed no clinical response, one — a 31-year-old woman — had an 85% reduction in swelling attack frequency with Ruconest. Specifically, her angioedema activity scores over 28 days (AAS28) decreased eightfold during treatment — accumulated score of 29 versus 233 — reflecting an overall improvement in symptoms.

Genetic screening revealed no genetic mutations to suggest she had hereditary angioedema, supporting an InH-AAE diagnosis.

Blood tests were conducted to monitor for biomarkers which may have suggested that bradykinin was involved in the patients’ swelling attacks. However, markers of blood clotting and inflammation were normal or slightly elevated, and levels of C1-esterase inhibitor and other related proteins were not changed with treatment.

No side effects or blood clots were reported in any patients during treatment with Ruconest.

After the trial, the single responsive patient restarted Ruconest and quickly achieved complete remission for six months. She then stopped Ruconest and switched to Xolair (omalizumab) and tranexamic acid due to health insurance limitations, which resulted in frequent and severe swelling attacks.

The woman again saw remission after restarting treatment with a human blood-derived C1-esterase inhibitor. After a year, she switched back to Ruconest, taken every five to six days.

Three of the other patients initiated Xolair and two were responsive to it.

The findings suggest Ruconest may be helpful in a subset of patients with idiopathic angioedema.

“In conclusion, [Ruconest] treatment was effective in 1 of 6 InH-AAE patients, and [Xolair] in 2 out of 4, suggesting a heterogeneous pathogenesis of [angioedema] and, consequently, the need for personalised treatment,” the researchers wrote.

The researchers suggested that perhaps bradykinin was not involved in the swelling attacks of the patients who didn’t respond to Ruconest, noting, however that “bradykinin cannot completely be ruled out as the main mediator of [angioedema].”

The study was partially funded by Pharming.