RARE Daily

Ionis Reports Publication of Positive Phase 2 data for Experimental HAE Therapy in NEJM

March 17, 2022

Ionis Pharmaceuticals published positive phase 2 data for donidalorsen, its experimental treatment for hereditary angioedema, in the New England Journal of Medicine.

Photo: Kenneth Newman, vice president of clinical development and leader of the immunology and pulmonology franchise at Ionis

In the phase 2 study, donidalorsen demonstrated a 90 percent reduction in angioedema attacks compared with placebo at the 80 mg monthly dose. There was significant improvement in quality of life as assessed by the Angioedema Quality of Life Questionnaire (AE-QoL) in the patients treated with donidalorsen.

Hereditary angioedema (HAE) is a rare and potentially fatal genetic disease that is characterized by rapid and painful attacks of inflammation in the hands, feet, limbs, face, abdomen, larynx, and trachea. HAE affects approximately 20,000 patients in the U.S. and Europe and can be fatal if swelling occurs in the larynx. In patients with frequent or severe attacks, doctors may use prophylactic treatment approaches to prevent and reduce the severity of HAE attacks.

Donidalorsen is Ionis’ wholly owned experimental antisense medicine designed to reduce the production of prekallikrein, which plays a key role in the activation of inflammatory mediators associated with acute attacks of HAE. Donidalorsen uses Ionis’ advanced Ligand-Conjugated Antisense (LICA) technology platform.

“Positive phase 2 data published in NEJM, along with data presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting, demonstrate that treatment with donidalorsen reduced attack frequency and disease burden of hereditary angioedema,” said Kenneth Newman, vice president of clinical development and leader of the immunology and pulmonology franchise at Ionis. “The promising findings from this study are particularly encouraging as we continue to advance the phase 3 clinical study for donidalorsen.”

The phase 2 study is double-blind and placebo-controlled in which patients with hereditary angioedema due to C1-inhibitor deficiency were randomized 2:1 to either 80 mg donidalorsen or placebo administered subcutaneously every 4 weeks for 16 weeks. The primary endpoint was the number of monthly angioedema attacks between weeks 1 and 17. Secondary endpoints included the time-normalized number of all, and only moderate or severe, angioedema attacks per month between weeks 5 and 17 and quality of life, measured with the AE-QoL. In this study, donidalorsen was safe and well tolerated.

The mean monthly rate of angioedema attacks was 0.23 and 2.21 in patients receiving donidalorsen and placebo, respectively. The mean attack rate between Weeks 5 and 17 was 0.07 in patients receiving donidalorsen and 2.06 for patients getting placebo.

Patients reported higher overall health-related quality of life (HRQoL) over 17 weeks with donidalorsen, with a mean change in total score of the AE-QoL of -26.85, compared with -6.15 in the placebo group where reduction in the score indicates better quality of life. There were improvements observed across all individual domains of the AE-QoL compared with placebo.

The majority of adverse events during the study were mild with a frequency that was similar between patients receiving donidalorsen and placebo groups. There were no deaths or serious adverse events. The most common treatment-emergent adverse events reported in patients treated with donidalorsen were headache (14.3 percent) and nausea (7.1 percent), both of which occurred at a higher incidence in the placebo group. None of the patients discontinued treatment due to adverse events.

Author: Rare Daily Staff

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