Lanadelumab Reduces Hereditary Angioedema Attacks, HELP Study Data Show

Lanadelumab, an antibody that binds and inhibits plasma kallikrein, effectively reduces the number of swelling attacks and improves quality-of-life scores in patients with hereditary angioedema (HAE) when used as a preventive treatment, new data from the Phase 3 HELP study shows.

The findings, which support the clinical benefits of lanadelumab as a preventive therapy, were presented recently during three poster sessions at the 2018 AAAAI/WAO Joint Congress, in Orlando, Florida.

Lanadelumab, developed by Shire, is an investigational human monoclonal antibody being investigated for the prevention of angioedema attacks in hereditary angioedema patients age 12 and older.

The antibody inhibits plasma kallikrein, an enzyme that is overactive in hereditary angioedema patients and leads to excess bradykinin, which is the protein behind swelling attacks.

The international, multi-center HELP study (NCT02586805) enrolled 125 patients with type 1 or type 2 hereditary angioedema. Participants were randomly assigned placebo or one of three lanadelumab dosing regimens – 150 mg every four weeks, 300 mg every four weeks, or 300 mg every two weeks – for a total treatment course of 26 weeks (about six months).

All three lanadelumab regimens led to a consistent reduction in monthly attack rates.

Researchers then analyzed patients based on the number of monthly attacks they had at baseline. Among the participants, 38 had one to fewer than two monthly attacks, 22 had two to fewer than three attacks, and 65 had three of more attacks per month.

For those with fewer attacks, lanadelumab’s regimens reduced the number of attacks by 51%, 80.4%, and 92.8%, respectively.

For patients with two to three attacks at baseline, the treatment reduced the attacks by 90.6%, 77%, and 88.2%.

Finally, among those experiencing more than three attacks per month, the attacks were reduced by 78.8%, 70.8%, and 85.9%, depending on the regimen they were receiving.

Patients who had been treated previously long-term with a C1-Inhibitor, and who were randomized to one of the three lanadelumab treatment groups, also showed a significant reduction in the monthly attack rates compared with those randomized to the placebo group.

The decrease in the attacks rate was similar to that of patients who were untreated for previous long-term preventive therapy.

Patients across all lanadelumab regimens also reported better health-related quality-of-life, compared to placebo-treated patients. This was assessed using an angioedema-specific quality-of-life (AE-QoL) questionnaire, administered every month.

A significantly higher number of patients treated with lanadelumab achieved minimal clinically important differences in total AE-QoL scores — 70% versus 37% for placebo.

“The data presented today further support the overall clinical profile of lanadelumab, which has been shown to significantly reduce the number of monthly HAE attacks when administered subcutaneously every two or four weeks,” Jennifer Schranz, Global Development Lead, HAE, Shire, said in a press release.

“HAE places a large burden on those living with the disease. We believe that this investigational treatment, if approved, has the potential to transform the treatment landscape for people with HAE,” she said.

“The data on lanadelumab continue to demonstrate the importance of controlling plasma kallikrein activity, which is chronically uncontrolled in those living with HAE — even between attacks,” said Marc Riedl, MD, an investigator in the trial.

“With its targeted mechanism of action, lanadelumab, if approved, has the potential to significantly reduce the number of monthly attacks for people with HAE,” said Riedl, who also is professor of medicine and clinical director at the US HAEA Angioedema Center at The University of California San Diego.

The U.S. Food and Drug Administration is evaluating lanadelumab for this indication. The application was granted priority review and the decision is expected by August.