information: Presentation of results at a congress
Announcement: presentation of results at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress
Company: Dyax (USA - MA), now Shire (UK - USA)
Product: DX-2930 - lanadelumab
- monoclonal antibody. DX-2930 is a novel, fully human monoclonal antibody that specifically binds and inhibits plasma kallikrein. It is being developed as a subcutaneous injection with a half-life of approximately 14 days in patients with hereditary angioedema. Uncontrolled pKal activity leads to excessive generation of bradykinin, a vasodilator thought to be responsible for the localized swelling, inflammation and pain characteristically associated with hereditary angioedema.
Disease: type 1 and type 2 hereditary angioedema (HAE)
area: Rare diseases - Genetic diseases - Hematological diseases
Country: Canada, Germany, Italy, Jordan, Puerto Rico, UK, USA
- The HELP study is a global, multi-center, randomized, double-blind placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab versus placebo over 26 weeks. The study population comprised 125 patients age 12 or older with HAE Type I or II who were randomized to one of four groups: 150 mg of lanadelumab every four weeks (150 mg Q4W), 300 mg every four weeks (300 mg Q4W), 300 mg every two weeks (300 mg Q2W), or placebo. (NCT02586805)
- • On March 3, 2018, Shire announced new Phase 3 results from the HELP Study™ will be highlighted in three poster presentation discussions at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Organization (WAO) Joint Congress. Patients in the study with ? 1 attacks per month were randomized into one of four treatment arms to receive repeated subcutaneous administrations of lanadelumab 300 mg every two weeks, 300 mg every four weeks, 150 mg every four weeks or placebo in a 2:1 (lanadelumab to placebo) ratio.Poster Presentation 151: Consistent Lanadelumab Treatment Effect in Patients with HAE Regardless of Baseline Attack Frequency in the Phase 3 HELP Study
Lanadelumab consistently achieved reductions in monthly attack rates compared to placebo, regardless of baseline attack rate and the dosing regimen. In this analysis, patients were categorized by baseline attack rate, 38 of the 125 patients in the trial had a baseline attack rate of 1 to ? 2 attacks per month. Compared to placebo (n=12), patients taking 150 mg every four weeks (n=10) had a 51% reduction in attacks, patients taking 300 mg every four weeks (n=9) had an 80.4% reduction, and patients taking 300 mg every two weeks (n=7) had a 92.8% reduction.
- Twenty-two patients had a baseline attack rate of 2 to < 3 per month. Compared with placebo (n=8), these patients had a 90.6% reduction in attack rates using 150 mg every four weeks (n=3), 77% with 300 mg every four weeks (n=5) and 88.2% with 300 mg every two weeks (n=6).
For patients with a baseline attack rate of ? 3 attacks per months (n=16), patients taking 150 mg every four weeks had a 78.8% reduction in attacks (n=15). Patients receiving 300 mg every four weeks experienced a 70.8% reduction (n=15). Patients receiving 300 mg every two weeks had an 85.9% reduction compared to placebo (n=21).
- Poster Presentation 150: Lanadelumab in Patients Switching from Long-Term Prophylaxis with C1-Inhibitor (C1-INH)
- This analysis of the HELP Study evaluated the efficacy of lanadelumab in patients who were previously using a C1-INH for long-term prophylaxis (LTP) and found that all lanadelumab dosing regimens significantly reduced attack rates versus placebo; the reductions were similar in magnitude to those who did not receive prior LTP. Patients 18 years of age and older who were previously on LTP underwent a two-week washout prior to entering the study.
- Poster Presentation 152: Lanadelumab Markedly Improves Health-Related Quality of Life in HAE Patients
- Health-related quality-of-life (HRQoL) was assessed as part of the HELP study using the Angioedema Quality-of-Life (AE-QoL) questionnaire, a validated, angioedema-specific instrument to measure impairment in HRQoL. The AE-QoL questionnaire was administered monthly; total and domain (functioning, fatigue/mood, fear/shame, and nutrition) scores were calculated. Responder rates were determined by use of the AE-QoL’s minimal clinically important difference (MCID=6).
The pooled lanadelumab group, which included patients across all dosing regimens, demonstrated a significantly greater reduction in total and domain AE-QoL scores, relative to placebo. The largest decrease in AE-QoL score (decrease indicates improvement) was observed in the functioning domain with a mean change of -29.28 for the pooled lanadelumab group compared to -5.41 for placebo. Items in the functioning domain included impairments in work, physical activity, spare time activities or social relations.
There was no evidence of a treatment effect for the EQ-5D-5L questionnaire, a non-validated, non-disease specific QoL tool.
In addition, a significantly higher proportion of patients in the pooled lanadelumab group achieved an MCID in total AE-QoL scores (70% versus 37% for placebo).
- • On May 18, 2017, Shire announced positive topline Phase 3 results for the HELP™ study, a global, multi-center, randomized, double-blind placebo-controlled parallel group trial that evaluated the efficacy and safety of subcutaneously administered lanadelumab versus placebo over 26 weeks in patients 12 years of age or older with Hereditary Angioedema (HAE). The study met its primary endpoint and all secondary endpoints with statistically significant and clinically meaningful results for all three lanadelumab treatment arms compared to placebo. The 300 mg dose administered once every two weeks resulted in a statistically significant reduction in mean HAE attack frequency of 87% compared to placebo. Results were consistent regardless of baseline attack rate. Notably for each of the three lanadelumab regimens studied, whether administered biweekly or monthly, a significantly higher proportion of patients—compared to placebo—were attack free throughout the entire 26 week study period.
- This study was representative of the full HAE disease spectrum. Overall, 52% of patients experienced three or more attacks per month at baseline, 65% of patients reported a history of laryngeal attacks and 56% were on long-term prophylaxis (LTP). Ninety percent of patients completed the study. Ninety-six percent of those who completed the study chose to roll-over into the ongoing long-term safety study (HELP™ Study Extension).
- Shire plans to submit a biologics license application (BLA) for evaluation by the FDA by late 2017 or early 2018.