Switching to donidalorsen brings fewer HAE swelling attacks: Study
Patients in clinical trial also reported improvements in quality of life
People with hereditary angioedema (HAE) types 1 and 2 had fewer swelling attacks and reported improvements in quality of life after they switched to donidalorsen from other preventive therapies, according to interim data from an ongoing clinical trial.
“The study was designed to provide patients and physicians with data to inform switching to donidalorsen, and the results support our belief that donidalorsen has the potential to be the prophylactic treatment of choice for HAE, if approved,” Kenneth Newman, MD, senior vice president of clinical development at Ionis Pharmaceuticals, said in a company press release. The findings were detailed in the study, “Donidalorsen Treatment of Hereditary Angioedema in Patients Previously on Long-Term Prophylaxis,” which was published in The Journal of Allergy and Clinical Immunology: In Practice. The study was funded by Ionis.
HAE types 1 and 2 are caused by mutations that impair the production or function of the C1-inhibitor (C1-INH) protein, low activity of which leads to the overproduction of bradykinin, a signaling molecule that triggers swelling. Swelling attacks are the primary symptom of HAE.
Donidalorsen is designed to reduce the levels of kallikrein, an enzyme involved in bradykinin production. Ionis is developing it as a preventive therapy to be injected under the skin to reduce the risk of swelling attacks in HAE.
Analyzing donidalorsen’s efficacy profile
A Phase 3 clinical trial called OASIS-HAE (NCT05139810) tested donidalorsen against a placebo in people with HAE types 1 and 2. Patients given the therapy had fewer swelling attacks and generally reported better life quality, results showed.
Bolstered by these findings, Ionis is seeking donidalorsen’s approval in the U.S. and a decision is expected next month. An application is also under review in Europe and a similar one in Canada is in the works.
After completing OASIS-HAE, participants could join an open-label extension study called OASISplus (NCT05392114), where they are all being treated with donidalorsen and monitored for long-term outcomes. OASISplus also enrolled dozens of people with HAE types 1 or 2 who were on other prophylactic treatments before switching to donidalorsen upon entering the trial. Researchers at Ionis and other institutions analyzed the outcomes for this specific group of patients.
The analysis included 65 patients, including 32 who switched to donidalorsen from Takhzyro (lanadelumab-flyo), 22 who switched from C1-INH concentrates, and 11 who’d previously been on Orladeyo (berotralstat).
Overall, the patients saw their attack rates drop by a mean of 62% after 16 weeks, or about four months, with donidalorsen.
On Takhzyro, patients had a mean of 0.69 swelling attacks a month. In the first few months after switching, their mean monthly swelling attack rate was 0.24, a 65% decrease. Similar results were seen with a C1-INH concentrate, where monthly swelling attack rates fell by a mean of 41% following the switch to donidalorsen, from 0.61 to 0.36. Patients who’d been on Orladeyo saw their mean monthly rate of swelling attacks fall by 73% — from 1.80 to 0.48.
Those who’d had more frequent swelling attacks before switching tended to see a more dramatic decrease after starting donidalorsen. There was no increase in HAE attack rates during the months when patients were transitioning from their previous therapies to donidalorsen, researchers said.
Patient-reported outcomes
Average scores on the Angioedema Quality of Life, an assessment of life quality, also improved after switching to donidalorsen, regardless of prior treatment. The proportion of patients with well-controlled disease, as measured by the Angioedema Control Test, also increased from 67% before the switch to 93% after it.
“In this study, we saw that patients were able to switch to donidalorsen from another prophylactic without an increase in attacks, and in fact, there was a reduction in mean attack rate. This translated to meaningful improvements in quality of life and disease control compared to baseline with their prior treatment,” Newman said.
Switching to donidalorsen was generally well tolerated, and no serious side effects related to donidalorsen were reported.
In a survey of 55 patients conducted at week 16, 84% patients said they preferred donidalorsen over their previous therapy, with 65% reporting a strong preference for it.
Their reasons for their preference varied, depending on what their other therapy had been. Those who’d been on Takhzyro most often said the injections were less bothersome and they had less injection-site pain or reactions, while those on C1-INH products reported less time to administer treatment. Patients who’d been on Orladeyo said donidalorsen helped control their disease better.
“At week 16, patients predominantly preferred donidalorsen to the prior treatment and reported higher satisfaction with the convenience and effectiveness of donidalorsen treatment,” wrote the researchers, noting the data “further support the safety and efficacy of donidalorsen for the treatment of [HAE types 1 and 2].”
The researchers did say the results were likely influenced by selection bias, a notable caveat, because patients who weren’t satisfied with their current treatment were probably more likely to enroll in the trial to try an experimental treatment. For this reason, the results probably can’t be generalized to everyone with HAE, they said.
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