Kiniksa Announces Positive Data from Phase 2 Trial of Mavrilimumab in Giant Cell Arteritis - Seite 2

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).

• Median time-to-flare by Week 26 could not be estimated in mavrilimumab recipients due to the low number of flares in the mavrilimumab treatment arm. The median time-to-flare for placebo recipients was 25.1 weeks. 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 at Week 26 was 33.3 percentage points higher in mavrilimumab recipients (83.2%) compared to placebo recipients (49.9%) (p=0.0038).
  

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.

The 12-week washout safety follow-up period and additional analyses of this Phase 2 trial are ongoing. Next steps for the development program in GCA will be further informed by anticipated discussions with the U.S. Food and Drug Administration (FDA).

“We believe there is significant unmet need for safe and effective giant cell arteritis therapies, given that approximately only half of patients can achieve sustained remission on a yearly basis on current standard of care,” said John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa. “Novel therapies which safely provide long-term sustained remission in this aging patient population with comorbidities are needed. Mavrilimumab, with its upstream inhibition of two immune pathways implicated in giant cell arteritis, has the potential to provide differentiation by addressing the underlying pathophysiology of the disease.”

Preclinical data, previously shown at scientific conferences and available through the Science section of Kiniksa’s website, support the mechanistic rationale of targeting the granulocyte macrophage colony stimulating factor (GM-CSF) pathway upstream in patients with GCA. GM-CSF and downstream T helper type 1 (T_H1) cell and T helper type 17 (T_H17) cell pathways were demonstrated to be activated at the ribonucleic acid and protein level in arteries from GCA patients compared to healthy controls, and mavrilimumab was demonstrated to inhibit production of inflammatory molecules characteristic of GCA pathophysiology in an ex vivo culture model of arteries from GCA patients¹. Additionally, in an in vivo model of human GCA, mavrilimumab reduced arterial inflammation and gamma interferon production².