Lanadelumab effective against hereditary angioedema attacks
Subcutaneous lanadelumab, a monoclonal antibody drug, for 26 weeks significantly reduces attack rates of hereditary angioedema, according to data published in JAMA.
The results of the trial supported the FDA approval of lanadelumab (Takhzyro, Dyax Corp.) for hereditary angioedema, a rare, potentially life-threatening disorder caused by genetic mutations associated with decreased levels of, or dysfunctional, C1 inhibitor protein.
“Our study and the subsequent FDA approval of lanadelumab have given patients with hereditary angioedema an important, novel option for preventive treatment,” Aleena Banerji, MD, of Massachusetts General Hospital, said in a press release. “Previously the only approved treatment options were oral androgens, which have significant side effects, and either IV or subcutaneous C1 inhibitor administration, which needs to be given twice a week. Subcutaneous lanadelumab, given once every 2 or every 4 weeks, is much easier for patients with an equally high level of efficacy.”
To evaluate the efficacy of lanadelumab in preventing hereditary angioedema attacks, Banerji and colleagues conducted a phase 3, randomized, double-blind, parallel-group, placebo-controlled study at 41 sites in Canada, the United States, Jordan and Europe. Participants were randomized 2:1 to receive either lanadelumab or placebo for 26 weeks. In addition, patients treated with lanadelumab were divided into three regimen groups: 150 mg every 4 weeks (n = 28), 300 mg every 4 weeks (n = 29) and 300 mg every 2 weeks (n = 27). A total of 41 participants received placebo.
Patients aged 12 years or older with hereditary angioedema type 1 or 2 completed a 4-week run-in period. Those who experienced one or more hereditary angioedema attack during this run-in were randomized. All patients included in the study received injections every 2 weeks. Participants in the every-4-week lanadelumab groups received a placebo between active treatments. Of the 125 randomized patients, 113 completed the study.
According to the researchers, the mean number of hereditary angioedema attacks per month, during the run-in period, among patients in the placebo group was four. Among patients in the lanadelumab groups, the mean number of attacks per month during this period was 3.2 for those who received 150 mg every 4 weeks, 3.7 for those who received 300 mg every 4 weeks, and 3.5 for those who received 300 mg every 2week 300-mg. During the treatment period, the mean number of attacks per month for the placebo group was 1.97. Among those treated with lanadelumab, the mean number of monthly attacks were 0.48 for the group receiving 150 mg every 4 weeks, 0.53 for the group receiving 300 mg every 4 weeks, and 0.26 for the group receiving 300 mg every 2 weeks.
The mean differences in the attack rate per month, compared to the placebo group, were –1.49 (95% CI, –1.9 to –1.08) in the every-4-week 150-mg group, –1.44 (95% CI, –1.84 to –1.04) every-4-week 300-mg group, and –1.71 (95% CI, –2.09 to –1.33) in the every-2-week 300-mg group. The most common adverse events that had greater frequency in the lanadelumab groups included injection site reactions and dizziness.
Following the study period, 109 participants entered an open-label trial extension, in which they began receiving 300-mg doses every 2 weeks.
“All participants in our trial — including those in the placebo group — can complete the open-label trial, which is anticipated to be finished in mid-2019,” Banerji said in the press release. – by Jason Laday
Disclosure: Banerji reports grants from Shire, as well as membership on advisory boards for Alnylam, BioCryst, CSL Behring, Pharming and Shire. Please see the study for all other authors’ relevant financial disclosures.