Completed IgAN studies

Efficacy in IgA nephropathy patients was initially assessed in a multi-center 16-patient, open-label, Phase 2a (NCT00767221) study in which patients received 8 mg NEFECON for six months, followed by a three-month follow-up. Patients in this study had a mean reduction in proteinuria of 23 per cent at end of treatment with a further reduction to 40 per cent two months after end of treatment; and an increase in eGFR of 8 per cent.

NEFECON was subsequently investigated in a 150 patient Phase 2b (NCT01738035) study that involved leading clinicians at 62 sites across ten countries in Europe. This study is still the largest completed double-blind study ever conducted with an experimental product in IgA nephropathy patients. It is also the only successful randomized, placebo-controlled Phase 2b study to date.

In the completed pan-European Phase 2b clinical trial, Nefecon was observed to statistically

significantly reduce proteinuria and to provide clinical benefit by preserving kidney function, as measured by estimated glomerular filtration rate, eGFR, which is considered a key metric for measuring kidney disease progression. This trial, known as NEFIGAN, was a double-blind, placebo-controlled trial in 150 patients randomized to receive either 8 mg or 16 mg per day of Nefecon or placebo, each on top of optimized RAS blockade to lower blood pressure, the predominant current standard of care. NEFIGAN achieved its primary endpoint of reduction in proteinuria for the 16 mg dose cohort. As measured by the urine protein creatinine ratio, or UPCR, patients in the placebo cohort exhibited an increase in proteinuria of 2.7%, while patients in the 16 mg dose cohort also exhibited statistically significant and clinically meaningful reductions in proteinuria of 27.3%. Patients treated with Nefecon also exhibited stabilization of eGFR, reflecting preservation of kidney function, while patients administered with placebo continued to show deterioration.

The trial findings supported NEFECON’s ability to counteract a decline in kidney function and potentially also promote a slight improvement. This suggests that NEFECON with its attractive efficacy / safety profile may have an important disease-modifying activity which could help delay onset of dialysis or potentially remove the need for such treatment.

IgAN Phase 3

Calliditas is currently conducting a global pivotal Phase 3 clinical trial in IgAN or Nefecon. The clinical trial ‘NefIgArd’ is designed to evaluate reduction of the surrogate marker proteinuria as its primary endpoint, which is the same endpoint used in NEFIGAN. NefIgArd is a randomized, double-blind, placebo-controlled, two-part Phase 3 clinical trial. Calliditas expects to report topline data from this trial in the fourth quarter of 2020.

The pivotal Phase 3 clinical trial in IgAN, NefIgArd, is designed to evaluate reduction of the surrogate marker proteinuria as its primary endpoint, which is the same endpoint used in the previously completed NEFIGAN clinical trial. The first patient in NefIgArd was randomized in November 2018. NefIgArd is a double-blind, placebo-controlled, two-part Phase 3 clinical trial. The first part, Part A, is a pivotal efficacy and safety trial expected to form the basis for submissions of a New Drug Application, or NDA, to the FDA and a Marketing Authorization Application, or MAA, to the EMA. The primary endpoint of Part A is the decrease in proteinuria in the first 200 randomized and dosed patients. In addition, a secondary endpoint of Part A is the difference in kidney function between treated and placebo patients as measured by eGFR. The topline results from Part A is expected to be reported in the fourth quarter of 2020.

If the topline data are positive, the intention is to file marketing applications in the first half of 2021 for accelerated approval in the United States by the FDA and conditional approval in the European Union by the EMA. The second part, Part B, is a post-approval confirmatory trial designed to validate proteinuria as a surrogate marker. Following completion of enrollment in Part A, recruitment of an additional 160 patients is continuing during 2020 in order to power Part B to assess the difference in kidney function between treated and placebo patients as measured by eGFR over a two-year period from the start of dosing of each patient, which is the same metric reported as a secondary endpoint in Part A over a one-year period. Data from Part B is expected to be reported in 2022. Across both parts, NefIgArd will enroll a total of 360 patients and generate nine months of dosing data, as well as an aggregate of 15 months of follow-up data from Parts A and B. If approved, the intention is to market and commercialize Nefecon in the United States as an on-label treatment specifically designed to have a disease-modifying effect for IgAN by preserving kidney function and thereby avoiding progression to ESRD.