Ionis reveals an oasis for HAE patients as RNA med reduces attacks in phase 3

We can now envision the oasis that Ionis Pharmaceuticals saw with its hereditary angioedema data.

Earlier this year, the company announced that donidalorsen had met the primary endpoint of a phase 3 study, but now we know it’s because the treatment spurred an 81% lower monthly rate of swelling attacks in patients who received the drug every four weeks.

Data from the OASIS-HAE and OASISplus studies also showed that 84% of patients who switched from previous prophylactic treatment preferred Ionis’ offering. Patients can administer the treatment themselves via auto-injector.

The therapy had a favorable safety profile, according to Ionis’ Friday announcement. The data will be presented at the 2024 European Academy of Allergy and Clinical Immunology Annual Congress in Valencia, Spain.

Ionis is taking the data to regulators to support an approval in HAE, a life-threatening condition that causes random swelling attacks to parts of the body. Donidalorsen is an RNA-targeting prophylactic therapy that reduces the production of prekallikrein, thereby interrupting the pathway that leads to HAE attacks.

“These data underscore the potential of donidalorsen to continually improve HAE attack rates and quality of life over time, positioning donidalorsen as an attractive potential treatment option,” said Ionis CEO Brett Monia, Ph.D. “In our prospective switch cohort, patients switched to donidalorsen from another prophylactic without increased breakthrough attacks and achieved greater disease control. In fact, a majority of patients who switched reported a preference for donidalorsen.”

Ionis previously reported in January that the OASIS-HAE study met its primary endpoint, with the rate of angioedema attacks at both the four-week and eight-week regimens of donidalorsen lower than the placebo cohorts.

The study featured patients receiving 80 mg of donidalorsen every four weeks or every eight weeks or placebo, with a total of 90 people across the cohorts. In the four-week cohort, which featured 45 patients, donidalorsen significantly reduced monthly attacks by 87% compared to placebo, which was a key secondary endpoint. The drug also reduced severe to moderate attacks per month by 89% in the same time frame and reduced attacks that required acute therapy by 92%.

At week 25, 91% of patients taking the drug in this group had well-controlled disease. While Ionis did not provide detailed data on the eight-week group, the company said patients had a similar benefit.

In the OASISplus study, an open-label extension and switch trial, attack rates continued to improve over time, with 93% and 92% improvements from baseline in the four-week and eight-week groups, respectively. Patients also had improved quality of life.

In a group of patients who previously switched over to donidalorsen, there was a 62% improvement in monthly attacks compared to baseline. Patients also managed the transition without breakthrough attacks.

William Blair analysts said donidalorsen has showcased a “highly competitive” profile with the latest cut of data. An approval in 2025 is expected as Ionis is planning to submit a new drug application soon.

“Ultimately, we see donidalorsen’s profile as generally superior to current prophylactic options, with less frequent dosing and at-home autoinjector dosing potential being further differentiators,” William Blair’s analysts wrote Friday morning.

The profile is comparable to CSL Behring’s garadacimab, which is under review for the indication with a decision expected by year end. However, garadacimab requires a loading dose administered in-office followed by monthly injections, whereas patients can self-administer donidalorsen, with the possibility of dosing every eight weeks.

Ionis is behind CSL Behring, but William Blair believes the market can handle multiple options. If Ionis captures a conservative 15% of the market, revenue could reach $450 million in the U.S. in 2030.

“We view today’s updates as positive for Ionis, with the current donidalorsen clinical profile appearing as good or better overall than available and other late-stage options, which is reinforced in data from the switch study showing a strong patient preference,” the analysts said.