Donidalorsen provides sustained HAE disease control: Trial data
Ionis Pharmaceuticals to seek treatment's FDA approval this year
Treatment with donidalorsen to prevent swelling attacks led to fewer of them and gains in quality of life for adults and teens with hereditary angioedema (HAE), according to final data from a Phase 3 trial and interim findings from its open-label extension study.
The patients who switched from other prophylactic therapies in the extension study also saw better disease control and most preferred donidalorsen over their previous treatment.
The findings from the Phase 3 trials OASIS-HAE (NCT05139810) and OASISplus ( NCT05392114) were discussed during oral presentations at the recent 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress. Data from OASIS-HAE were also published in The New England Journal of Medicine in “Efficacy and Safety of Donidalorsen for Hereditary Angioedema.”
Developer Ionis Pharmaceuticals plans to seek regulatory approval of donidalorsen as a prophylactic treatment for HAE in the U.S. this year. Otsuka Pharmaceuticals, which holds exclusive rights to commercialize the therapy in Europe, is preparing a similar submission.
“We’re delighted by the results from the OASIS clinical program, which we believe position donidalorsen to advance the prophylactic treatment paradigm for people living with HAE,” Brett Monia, PhD, Ionis CEO, said in a company press release. “We look forward to launching it as part of our growing independent commercial pipeline, if approved.”
Donidalorsen is designed to prevent the swelling attacks that appear in HAE by interfering with the pathway that leads to the production of the signaling molecule bradykinin, which is implicated in those attacks. Donidalorsen blocks the production of a molecule in that cascade, called prekallikrein.
Fewer swelling attacks with donidalorsen
OASIS-HAE enrolled 91 patients, ages 12 and older, with HAE type 1 or 2, who were having recurrent swelling attacks. They were randomly assigned to receive 80 mg of donidalorsen or a placebo as an injection under the skin, or subcutaneously, once every four weeks or eight weeks for about six months.
As reported, both donidalorsen dosing regimens were associated with significant reductions in HAE attack rates compared with a placebo, which met the trial’s main goal.
Monthly attack rates were reduced by 81% relative to a placebo with once monthly dosing and by 55% with dosing every other month.
From weeks five to 25, monthly treatment significantly reduced attack rates by 87% relative to a placebo, meeting a key secondary goal. In that time, moderate to severe attacks were reduced by 89%, and attacks that required on-demand therapy by 92%. Benefits observed in the every other month dosing group were similar, but not as strong.
After about six months, 91% of the patients given monthly donidalorsen and 74% who received it every two months reported having well-controlled HAE, compared with 41% of those on a placebo.
The treatment was also associated with clinically significant improvements in quality of life, lower incidence of visits to the emergency room, and greater drops in prekallikrein levels relative to a placebo.
After the main trial, 94% of participants from OASIS-HAE entered OASISplus and are all receiving donidalorsen, either once monthly or once every two months.
Interim analyses presented at the conference showed that reductions in HAE attack rates observed in the main trial were sustained for up to a year in OASISplus. HAE attack rates similarly dropped for those patients initially on a placebo once they switched to the monthly dosing regimen of the active medication. Most reported their disease is well controlled and gains in life quality have been sustained.
OASISplus also included a new group of 64 HAE patients who’d been on a stable dose of other prophylactic treatments, including C1 esterase inhibitors, Orladeyo (berotralstat), and Takhzyro (lanadelumab), for at least three months. All switched to monthly donidalorsen in the trial.
Interim results covering up to 17 weeks, which is a little more than four months, showed that these patients had a 62% reduction in mean monthly HAE attack rates relative to their previous treatment.
Most (84%) reported they preferred donidalorsen over their previous treatment, regardless of what they’d been on, and the reasons they gave included better disease control, less time to administer, and less injection site pain or reactions. On a prior prophylaxis, 50 to 74% of the patients said their disease was well controlled, whereas more than 90% reported this on donidalorsen. Improvements in life quality scores on donidalorsen were also observed.
Donidalorsen was well tolerated across the main trial and extension without causing serious treatment-related side effects. Injection site reactions and headache were the most common side effects related to donidalorsen in the main trial. No new safety issues were identified in the extension.
“The comprehensive OASIS clinical program demonstrates how donidalorsen can potentially address key concerns patients may experience with currently available treatment options,” said Kenneth Newman, MD, senior vice president of clinical development at Ionis. “We believe that donidalorsen has a unique profile that may address the needs of people with HAE.”
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