Giant cell arteritis (GCA) is a chronic inflammatory disease of medium-large arteries.
Monoclonal antibody targets granulocyte macrophage colony-stimulating factor receptor alpha (GM-CSFRα) and inhibits the signaling of granulocyte macrophage colony-stimulating factor (GM-CSF).
GM-CSF is a key growth factor and cytokine that can govern the development and function of dendritic cells, monocytes, macrophages, and granulocytes (eg, neutrophils, basophils, and eosinophils).
We estimate that there are approximately 75,000 to 150,000 patients with GCA in the United States.
Orphan Drug designation granted by the US Food and Drug Administration (FDA) for mavrilimumab for the treatment of giant cell arteritis.
We believe that by blocking GM-CSF signaling, mavrilimumab may be able to reverse the course of GCA by upstream targeting of the cell types driving the inflammatory process, a mechanism that is different from currently available therapies.
The Phase 2 trial randomized 70 patients 3:2 to mavrilimumab 150 mg (N=42) or placebo (N=28) biweekly injected subcutaneously, co-administered with a protocol-defined 26-week oral corticosteroid taper. Patients were stratified by new onset (n=35) or relapsing/refractory (n=35) disease.
The primary efficacy endpoint of time-to-first adjudicated GCA flare by Week 26 in all treated patients was statistically significant (Hazard Ratio = 0.38, p=0.0263). There was a 62% lower risk of flare in mavrilimumab recipients compared to placebo recipients.
The secondary efficacy endpoint of sustained remission at Week 26 in all treated patients was also statistically significant. The sustained remission rate was a 33.3 percentage points higher in mavrilimumab recipients (83.2%) compared to placebo recipients (49.9%) (p=0.0038).
While the study was not powered for disease cohorts, there was a consistent trend of efficacy across the new onset and relapsing/refractory cohorts.
Mavrilimumab was well-tolerated; there were no drug-related serious adverse events, and the rates of drug-related treatment-emergent adverse events between mavrilimumab recipients and placebo recipients were similar.
A 12-week washout safety follow-up period is ongoing, and additional analyses of this Phase 2 trial are planned.
Kiniksa expects to provide next steps for mavrilimumab, including for giant cell arteritis (GCA), in the first half of 2021.
COVID-19 Pneumonia and Hyperinflammation
In the Phase 2 portion of a Phase 2/3 trial of mavrilumuab in severe COVID-19, a 116 non-mechanically ventilated patients were randomized in a 1:1:1 ratio to receive a single intravenous (IV) dose of mavrilimumab 10 mg/kg, 6 mg/kg or placebo. Data showed that patients treated with mavrilimumab demonstrated a reduction in mechanical ventilation and death at Day 29 pooled across dose levels. Clinical improvement was observed on top of steroids and/or antivirals. Mavrilimumab was well-tolerated and exhibited a favorable safety profile.
Kiniksa continues to enroll patients in the Phase 3 portion of the Phase 2/3 clinical trial of mavrilimumab in severe COVID-19 pneumonia and hyperinflammation.
Corticosteroids are the mainstay for the treatment of GCA, but approximately 50% to 70% of patients are corticosteroid refractory or corticosteroid dependent. Long-term administration of corticosteroids carries significant morbidity, especially in an elderly population such as in those with GCA. The FDA recently approved an inhibitor of IL-6 activity as an adjunct to a corticosteroid taper for the treatment of GCA; however, IL-6 production is downstream of GM-CSF and does not address all of the underlying causes of inflammation.