Everest Medicines' Partner Calliditas Therapeutics Announces Nefecon® the Only FDA-approved Treatment for IgA Nephropathy to Significantly Slow Kidney Function Decline

Everest Medicines's licensing partner Calliditas Therapeutics AB announced that the U.S. Food and Drug Administration (FDA) had approved Nefecon^® delayed release capsules to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. Nefecon^® was first approved in December 2021 under the FDA accelerated approval pathway and is now the first fully FDA-approved treatment for IgAN based on a measure of kidney function.

• The FDA approval is for adults with primary IgAN who are at risk for disease progression, irrespective of proteinuria levels.
• Nefecon^® is now approved by the FDA with a confirmed and statistically significant benefit over placebo (p<0.0001) in estimated glomerular filtration rate (eGFR) over the two-year period that consisted of 9 months of treatment with Nefecon^® or optimized RASi and a 15-month follow-up off drug.
• At 2 years, there was a 6.11 mL/min/1.73 m² decline in eGFR in the Nefecon^® group compared with a 12.0 mL/min/1.73 m² decline in the placebo group (p<0.0001), representing 50% less deterioration of kidney function in Nefecon^® -treated patients compared to placebo-treated patients over the 2-year period.
• Nefecon^® is a B-cell immunomodulator designed to target the origin of the disease and reduce the production of pathogenic galactose-deficient IgA1 antibodies, which cause IgAN.
• Nefecon^® was approved by China's National Medical Products Administration in November 2023. Results from Chinese subpopulation analysis demonstrated a numerically greater magnitude of Nefecon^® treatment effect over placebo in kidney function, proteinuria and microhematuria compared to the global population.

"We congratulate our partner on the full FDA approval of Nefecon^®, which confirms the drug's capability to preserve kidney function and significantly delay disease progression. This first-ever fully FDA-approved treatment for IgAN represents a beacon of hope for the entire IgAN community globally," said Rogers Yongqing Luo, Chief Executive Officer of Everest Medicines.  "On the back of this important milestone, we are excited to be launching this first-in-disease treatment in China in the first quarter of 2024. China has the largest population of IgAN patients in the world with more rapid disease progression, and we are very happy to have the solution to address this urgent need."

"Nefecon^® represents a revolutionary therapeutic option for Chinese patients who have more rapid disease progression in IgAN with no effective treatment options. This medicine offers patients a truly disease modifying treatment with sustained and clinically meaningful reduction in eGFR declines along with durable proteinuria reduction. The FDA full approval and the China approval allow physicians to take more proactive measures in managing the impact of the disease to preserve kidney function," said Professor Zhang Hong at Peking University First Hospital, a member of the global steering committee for the Phase 3 NefIgArd clinical trial. "Based on the exciting results in both efficacy and safety in the Chinese population observed from the NefIgArd trial, we believe Nefecon^® will bring significant changes to Chinese patients with IgAN."

In the global Phase 3 trial, Nefecon^® demonstrated a highly statistically significant and clinically relevant benefit compared to placebo in eGFR over the two-year period. The reduction in UPCR observed with Nefecon^® treatment was also durable and the proportion of patients with microhematuria in the Nefecon group declined. Nefecon^® was also generally well-tolerated in the Phase 3 clinical trial.

Further subpopulation analysis from the NefIgArd clinical trial showed a numerically greater treatment effect in kidney function prevention, proteinuria reduction and microhematuria improvement in the Chinese subpopulation compared to the global population. The mean absolute change from baseline in eGFR at 24 months showed approximately 66% less deterioration in kidney function with 9-month Nefecon^® treatment compared with a smaller preservation of kidney function (50%) in the global population. Patients treated with Nefecon^® in China showed a 43% greater reduction (95% CI 8%, 65%) in UPCR compared with placebo at 24 months and a 31% greater reduction (95% CI 0, 53) at 9 months.  In the global population, Nefecon^® treatment provided an approximately 30% greater reduction in UPCR at both 24 months and 9 months compared to placebo. The proportion of Chinese patients without microhematuria in the Nefecon^® group increased from 26.9% at baseline to 57.7% during observational follow-up, while it was maintained at 14.3% in the placebo group.