Donidalorsen may improve quality of life for people with HAE
FDA is reviewing request to approve therapy as preventive treatment
Donidalorsen, a preventive therapy being developed to reduce the frequency of swelling attacks for people with hereditary angioedema (HAE), significantly improved quality of life and symptom control for people with the condition, a new analysis of clinical trial data suggests.
Ionis Pharmaceuticals, donidalorsen’s developer, funded the study, “Patient-Reported Outcomes in the Phase III OASIS-HAE Study of Donidalorsen for Hereditary Angioedema,” which was published in Allergy.
In HAE, recurrent swelling attacks can affect different parts of the body and are typically caused by the overproduction of bradykinin, a signaling molecule that causes blood vessels to leak fluid into nearby tissues. Donidalorsen is an antisense oligonucleotide therapy made to interfere with the molecular pathways that lead to bradykinin’s production, bringing its levels back into check, and preventing or reducing the frequency of swelling attacks.
The U.S. Food and Drug Administration is reviewing a request to approve donidalorsen as a preventive treatment for HAE attacks and a decision is expected in August. The application was partly supported by data from the Phase 3 OASIS-HAE trial (NCT05139810), which showed donidalorsen could decrease swelling attack frequency.
That study assessed the safety and efficacy of donidalorsen in HAE patients, ages 12 and older. Its participants were randomly assigned to receive injections under the skin of donidalorsen or a placebo, given every four or eight weeks, for 24 weeks.
Gains in four-week group higher than eight-week, placebo groups
In this analysis, the researchers reviewed self-reported outcomes from 90 participants in OASIS-HAE to assess the therapy’s impact on quality of life and disease control.
They found that 88.1% of the participants who received donidalorsen every four weeks saw a clinically meaningful improvement on the Angioedema Quality of Life Questionnaire score, defined as a reduction of at least 6 points. This was significantly higher than the placebo group, where 45% of the patients met that criteria. The AE-QoL is a patient-reported measure of health-related quality of life. Most patients who received donidalorsen every eight weeks achieved the same outcome (71.4%), but the difference from the placebo group wasn’t statistically significant.
Patients in both treatment groups said their ability to complete daily activities improved. Feelings of fear and shame and concerns about nutrition also eased more in these groups than the placebo group. This shows “donidalorsen patients felt less anxiety/embarrassment around their HAE attacks and fewer limitations with food choices,” the researchers wrote.
The patients were also asked to complete the Angioedema Control Test to rate how well they felt their disease was under control. In the four-week treatment group, 91% of participants said their disease was well controlled by the end of the study, as did 74% in the eight-week group. Less than half of the placebo-treated participants reported this level of disease control.
Those treated with donidalorsen tended to perceive their disease as being less severe at the end of the trial than at the beginning. Compared with 44% of people in the placebo group, 82% who received donidalorsen injections every four weeks believed their disease became less severe. While 55% of participants in the eight-week group showed improvements in self-perceived disease severity, this wasn’t significantly different from the placebo group.
The patients in the four-week group also saw significant gains in work or school productivity, and had fewer activity impairments over those in the placebo group. The same trends were seen in patients in the eight-week group, but they didn’t reach statistical significance.
The smaller size of the eight-week treatment group may have contributed to the lack of statistical significance in many metrics, despite the overall improvements, the researchers said.
“Donidalorsen significantly reduced disease burden for patients with HAE by improving [quality of life], increasing disease control, and improving their ability to participate in work, school, and other normal activities of daily life,” they wrote.
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