Ionis finds relief for HAE patients with RNA drug in phase 3

In recent developments, Ionis Pharmaceuticals is making significant strides with its hereditary angioedema (HAE) treatment, donidalorsen. Earlier in the year, the company had announced promising results from a phase 3 study, revealing that donidalorsen considerably reduced the frequency of swelling attacks in patients who received the drug every four weeks. Specifically, it led to an 81% reduction in monthly attack rates.

The OASIS-HAE study had previously met its primary endpoint, demonstrating lower angioedema attack rates for patients on both the four-week and eight-week regimens of donidalorsen compared to those on placebo. Participants in this study were administered 80 mg of donidalorsen every four or eight weeks, across a total cohort of 90 individuals. Among these, the four-week cohort, consisting of 45 patients, saw an 87% reduction in monthly attacks compared to the placebo group. Furthermore, this regimen reduced severe to moderate attacks by 89% and cut down attacks needing acute therapy by 92%. By the 25th week, 91% of these patients had their disease well-controlled.

Additionally, data from the OASISplus study, an open-label extension and switch trial, showed continued improvement over time. Attack rates improved by 93% and 92% from baseline in the four-week and eight-week groups, respectively. The study also highlighted an improved quality of life for patients. For those who switched to donidalorsen from other prophylactic treatments, there was a 62% reduction in monthly attacks compared to baseline, and patients managed the transition without experiencing breakthrough attacks.

Ionis has shared that donidalorsen, an RNA-targeting prophylactic therapy, works by reducing the production of prekallikrein, thereby interrupting the pathway leading to HAE attacks. The therapy has also demonstrated a favorable safety profile. Importantly, 84% of patients who transitioned from previous prophylactic treatments preferred donidalorsen, which can be self-administered via an auto-injector. This data will be presented at the 2024 European Academy of Allergy and Clinical Immunology Annual Congress in Valencia, Spain.

Brett Monia, Ph.D., CEO of Ionis, emphasized the potential of donidalorsen to enhance HAE attack rates and improve the quality of life over time. Monia pointed out that patients who switched to donidalorsen from other prophylactic treatments achieved better disease control without an increase in breakthrough attacks. Many of these patients expressed a preference for donidalorsen.

According to William Blair analysts, donidalorsen has demonstrated a highly competitive profile with these latest data. An approval for the treatment is anticipated in 2025, as Ionis is preparing to submit a new drug application. The analysts noted that donidalorsen’s profile appears superior to current prophylactic options due to its less frequent dosing and the convenience of at-home auto-injector administration.

While CSL Behring's garadacimab, a competing treatment, is also under review, it requires an initial in-office loading dose, followed by monthly injections. In contrast, donidalorsen offers the possibility of dosing every eight weeks, with the added convenience of self-administration.

Despite being behind CSL Behring in the race, William Blair analysts believe the market can accommodate multiple treatment options. They project that if Ionis captures a conservative 15% of the market, the company could see revenues of $450 million in the U.S. by 2030. They regard the recent updates as very positive for Ionis, reinforcing the clinical profile of donidalorsen as good, if not better, than existing and other late-stage options. This is further supported by data from the switch study showing strong patient preference for donidalorsen.