Preventive treatment reduces HAE swelling attacks by 84% in real world
Long-term study also shows longer dosing intervals for over half of patients
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Long-term preventive treatment with Takhzyro (lanadelumab-flyo) — approved in the U.S. and the European Union for nearly a decade — substantially reduces the rate of swelling attacks in people with hereditary angioedema (HAE) treated in routine clinical practice.
That’s according to the final results of a Phase 4 study dubbed ENABLE, which tested the injection therapy in HAE patients across Europe and the Middle East to assess its real-world effectiveness. The trial data showed that, over an average of about 2.4 years, the observed monthly HAE attack rate for individuals on Takhzyro fell by 84%.
Moreover, patients reported better disease control and quality of life, less fatigue and anxiety, and improved work productivity and daily functioning, the researchers noted.
Additionally, the use of Takhzyro resulted in greater treatment satisfaction, per the study. And more than 60% of participants were able to extend their dosing intervals by the one-year mark, with no new safety signals identified, the data showed.
Overall, these real-world findings “support the benefits of [Takhzyro] for patients with HAE and its use as first-line [long-term preventive treatment], as recommended by the most recent HAE management guidelines,” the researchers wrote.
The study, “Sustained Effectiveness of Lanadelumab in Preventing Hereditary Angioedema Attacks: The ENABLE Study,” was published in the journal Clinical and Translational Allergy. It was sponsored by Takeda, which markets Takhzyro. Four of the study’s 16 authors are employed by the company.
HAE is a rare disorder characterized by recurrent, unpredictable swelling attacks. Most cases of HAE are caused by a deficiency of a protein called C1 inhibitor (C1-INH), either because the body does not produce enough functional protein or because the protein does not work properly. When C1-INH activity is insufficient, a signaling molecule called bradykinin is produced in excess, driving the swelling seen in HAE attacks.
Takhzyro is now widely approved as long-term preventive treatment for HAE. The antibody-based therapy, which is administered via a subcutaneous or under-the-skin injection, works by blocking plasma kallikrein, an enzyme involved in the production of bradykinin, thereby preventing its overproduction.
Trial tested preventive treatment for up to 3 years
Following its approval, the Phase 4 ENABLE trial (NCT04130191) was launched to evaluate Takhzyro’s long-term effectiveness and safety in real-world clinical practice across 18 locations in Europe and the Middle East.
Now, researchers have reported the final data from ENABLE.
The study involved 138 people, ages 12 and older, enrolled in Austria, Germany, Israel, Italy, Kuwait, Spain, and Switzerland. The participants were followed for up to three years. The main goal was to compare HAE attack rates during Takhzyro treatment with those recorded in the three months before treatment started. Safety, quality of life, disease control, and other patient-reported outcomes were also assessed.
All participants started Takhzyro at a dose of 300 mg every two weeks.
The mean patient-reported attack rate fell from 3.88 attacks per month before Takhzyro to 0.30 per month during treatment. Using a statistical model that accounted for different lengths of observation before and during treatment, the researchers estimated a mean 93% reduction in patient-reported attack rates. Physician-reported attack data showed a similar pattern, with a mean decline of 83%.
After starting Takhzyro, 82 patients (59%) were attack-free during at least one four-week period. By comparison, patients (9%) had been attack-free for a month during the three-month period before starting treatment.
Among attacks during treatment for which severity information was available, at least 80% were mild or moderate, and about 70% were treated, most often with C1-INH therapy or icatibant (sold as Firazyr).
The researchers noted that patients’ treatment schedules changed over time. After six months, 28% of participants had extended the interval between Takhzyro doses, with 61% increasing their dosing interval by month 12. Overall, 69% of patients had at least one dosing-interval change during follow-up, the data showed.
Quality of life, work productivity improve with Takhzyro
Before starting Takhzyro, patients generally perceived their HAE as poorly controlled, as measured by the Angioedema Control Test (AECT), and reported moderate-to-large impairments in health-related quality of life (HRQoL), based on the Angioedema Quality of Life (AE-QoL) questionnaire.
After just one month of treatment, about 80% of assessed patients had AECT scores indicating adequately controlled disease, the data showed. Clinically meaningful improvements in AE-QoL scores were also evident at one month and were sustained over time, the researchers noted.
Fatigue, measured with the Fatigue Severity Scale, and anxiety, assessed with the Hospital Anxiety and Depression Scale, also eased after treatment began and continued to decrease over time, the data showed.
In addition, work productivity improved, per the data. Before Takhzyro, adults in the study reported a mean 39.5% loss in overall work productivity, which fell to 19% after one month of treatment. Activity impairment dropped from 41.3% to 27.1% over the same period, while treatment satisfaction increased, per the data.
Findings from ENABLE demonstrated the long-term effectiveness of [Takhzyro] in clinical practice; substantial reductions in HAE attack rates and improvements in patient-reported [health-related quality of life] were maintained for up to 36 months.
Regarding safety, 69% of patients experienced treatment-emergent adverse events during follow-up, but most were considered unrelated to Takhzyro, according to the researchers.
Treatment-related events occurred in 25 patients (18%) and were nearly all mild or moderate. Injection-site reactions were the most common treatment-related side effect, affecting 12% of participants. No adverse events were fatal or caused patients to discontinue treatment or leave the study, the researchers noted.
“In conclusion, findings from ENABLE demonstrated the long-term effectiveness of [Takhzyro] in clinical practice; substantial reductions in HAE attack rates and improvements in patient-reported HRQoL were maintained for up to 36 months. The safety profile of [Takhzyro] was consistent with previous studies and no new safety signals were recorded,” the researchers wrote.
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