"The positive findings from biomarker and patient subgroup analyses from the Phase 3 NefIgArd study highlights that Nefecon^® treatment results in a coordinated immunological response with the potential to modulate the intestinal immune network responsible for IgA production. They also reinforced Nefecon^®'s ability to slow kidney function decline by targeting the origin of the disease," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines. "Everest participated in the NefIgArd study, and plans to publish the Chinese subpopulation data in a future medical conference. We look forward to bringing this differentiated and disease-modifying treatment to more Asian patients soon."

Biomarker Analyses

IgA-containing immune complexes (IgA-IC) have previously been shown to accumulate in renal tissue, where they trigger inflammation and scarring of the glomeruli. Investigation of the effect of Nefecon^® on circulating levels of IgA-IC in the Part A population of the NefIgArd clinical trial (n=160) revealed that patients treated with Nefecon^® 16mg/day exhibited a statistically significant decrease in IgA-IC levels compared to patients who received placebo when evaluated at the 3-, 6- and 9-months post randomization. Suppression by treatment with Nefecon^® of both IgA-IC formation and galactose-deficient IgA1 as previously reported offers an unprecedented opportunity to target the fundamental immune abnormalities that drive IgA deposition in the kidney and development of IgAN.

An additional analysis of the 160 patients enrolled in Part A of the Phase 3 NefIgArd clinical study was conducted to assess the levels of three soluble factors known for modulating B cell maturation in gut-associated lymphoid tissue (GALT): B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and serum B-cell maturation antigen (sBCMA). Compared to placebo, levels of BAFF were decreased at 3-, 6-, and 9-months after treatment initiation. Levels of APRIL were significantly reduced at the 3- and 6-months timepoints and levels of sBCMA were decreased at the 6-months timepoint. These data further support the potential disease-modifying effect of Nefecon^® in IgAN and reinforce the central role of the gut–kidney axis in the pathogenesis of IgAN.

To further understand the impact of Nefecon^® on chemokine signaling in IgAN patients, the levels of three circulating chemokines known to be present in the intestinal tract at the site of IgA production, CXCL5, CCL13 and CCL11, were assessed in the Part A patient population portion of the NefIGArd trial (n=160). Compared to placebo, the analyses showed that treatment with Nefecon^® 16 mg/day resulted in a statistically significant decrease in the levels of CXCL5 and CCL13 and an increase in levels of CCL11 at 3-, 6- and 9-months after treatment initiation. These biomarker data provide additional evidence for a mucosal mechanism of action of Nefecon^® in IgAN and support previous observations that disordered lymphocyte trafficking and mucosal dysregulation likely contribute to the pathogenesis of IgAN.

Patient Subgroup Analyses

The full two-year results of the Phase 3 NefIgArd trial (n=364 patients) were further analyzed to assess potential differences in response to Nefecon^® treatment based on self-reported Asian (n=83) or White (n=275) ancestry in patients with IgAN. Treatment with Nefecon^® 16 mg/day over a 9-month period resulted in clinically meaningful preservation of kidney function in both subgroups, as evidenced by reduction in proteinuria and stabilization of eGFR in these two subgroups when compared to placebo subgroups.

Nefecon^® has already been approved and marketed in the United States, the European Union and the UK. The NDA for Nefecon^® in mainland China is currently under Priority Review and is expected to be approved in the second half of this year. It was the first non-oncology medicine to receive Breakthrough Therapy Designation in China, reinforcing the urgent need of Nefecon^® as a first-in-disease therapeutic option in the nation.  Nefecon^® has been available for clinical use in Shanghai Ruijin Hospital's Hainan subsidiary through an early-access program since April.