Ionis’ HAE drug bests placebo in phase 3, setting up run to FDA approval

Ionis Pharmaceuticals’ investigational treatment for hereditary angioedema (HAE) has hit the primary endpoint of a phase 3 trial, allowing the biotech to ready its approval application to the FDA.

The global study involved 91 patients aged 12 years and above with type 1 or type 2 HAE receiving either a 80 mg dose of donidalorsen via subcutaneous injection once every four weeks or every eight weeks for 24 weeks, or placebo. The rate of angioedema attacks at both the four-week and eight-week regimens of donidalorsen were lower than the placebo cohorts—with p values or 0.001 and 0.004, respectively—hitting the trial’s primary endpoint.

California-based Ionis also reported “statistical significance on all secondary endpoints” for the four-week cohort as well as hits on “key” secondary endpoints for the eight-week group. “Donidalorsen demonstrated a favorable safety and tolerability profile in the study, and there were no serious adverse events in the patients treated with donidalorsen,” the company added in the Jan. 22 release.

The RNA-targeted medicine is designed to halt the production of prekallikrein (PKK), interrupting the pathway that leads to attacks among patients with the rare genetic disease. Last month, Ionis sold the European rights to the drug to Otsuka Pharmaceutical for $65 million upfront.

At the time, William Blair analysts called Ionis’ move to focus on its own rare disease drug launch efforts in the U.S. while seeking partners outside of the country as “a prudent use of resources,” and said they saw “sound commercial potential for donidalorsen.”

Based on today’s data, Ionis said it is now preparing to submit a new drug application with the FDA, while Otsuka is readying its own application for the European Medicines Agency. Ionis’ IND application for donidalorsen will follow hot on the heels of its AstraZeneca-partnered transthyretin amyloidosis (ATTR) drug Wainua, which secured an FDA nod at the end of last year.

"These data represent our third highly positive phase 3 readout over the last 12 months, underscoring the strength of our LICA platform for RNA-targeted medicines," Ionis CEO Brett Monia, Ph.D., said in today's release. “Following the recent launch of Wainua, we are now well on our way to independently launching medicines from our wholly owned pipeline with regulatory submissions this year for olezarsen in familial chylomicronemia syndrome and donidalorsen in HAE.”

If approved, donidalorsen will be going up against CSL Behring’s Haegarda, BioCryst's Orladeyo and Takeda’s Takhzyro, while potential competitors from the likes of Pharvaris and Intellia are waiting in the wings. Despite this “increasingly crowded space,” William Blair analysts said in a note in November that they continued to “see donidalorsen as a potentially differentiated … growth driver for Ionis.”