Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) (“Calliditas”), today announced data presentations highlighting additional analyses from the Phase 3 NefIgArd study with Nefecon in adults with primary IgA nephropathy (IgAN), as well as pre-clinical data on the treatment of Alport syndrome with setanaxib, a novel NOX inhibitor, presented at the American Society of Nephrology (ASN) Kidney Week 2023 in Philadelphia, PA on November 1-5, 2023.
“The additional analyses of data from the NeflgArd Phase 3 trial that we and our scientific collaborators presented at ASN Kidney Week showcased our commitment to advancing the science in understanding IgA nephropathy and to shaping a better future for patients with rare diseases,” said Richard Philipson, Chief Medical Officer at Calliditas.
Oral Presentation Analyses
NefIgArd Phase 3 Trial full analysis
The Phase 3 double-blind, randomized NefIgArd study evaluated the impact of Nefecon, a novel targeted-release formulation of budesonide, vs placebo on eGFR in adults with IgAN. The 2-year study period consisted of nine months of treatment with Nefecon (16 mg/day) or placebo, followed by a 15-month follow-up period off the study drug. The full analysis of the 364 patients randomized 1:1 to Nefecon or placebo showed:
- A statistically significantly smaller proportion of Nefecon-treated patients saw a 30% eGFR reduction compared to placebo-treated patients
- A delayed progression to a confirmed 30% eGFR reduction was observed in the Nefecon arm compared to the placebo arm
- Use of rescue medication did not alter the response to Nefecon vs placebo according to a pre-defined analysis
Late-Breaking Poster Presentation Analyses
NefIgArd Phase 3 trial population sub-analysis
The 2-year NefIgArd trial included 62 patients with IgAN from mainland China (n=32 in Nefecon arm, n=30 in the placebo arm), with similar baseline characteristics as the global study population. In these patients, Nefecon treatment for 9 months resulted in:
- Lower time-weighted average change in eGFR from baseline in the Nefecon arm
- 66% less deterioration in renal function over the 2-year study period in the Nefecon arm, as well as reduced 2-year eGFR total slope
- 31% greater mean reduction in urine: protein creatinine ratio at 9 months in patients treated with Nefecon vs placebo, which was sustained at 2 years
- A higher proportion of Nefecon-treated patients did not display microhematuria during the observational follow-up period compared to patients who received placebo
Poster Presentations Analyses
Additional analyses were conducted from Part A of the Phase 3 NefIgArd trial(n=160)
- Serum samples collected from patients enrolled in Part A of the NefIgArd study were analyzed for functional protein interaction and showed that Nefecon modulates serum biomarkers associated with proteins known to play a role in the intestinal immune network for IgA production and control of B cell activation. These data further support a disease-modifying effect of Nefecon at the site of IgA synthesis and reinforce the link between the ileal gut-associated lymphoid tissue (GALT) and the kidneys.
- Levels of circulating anti-gliadin IgA and anti-casein IgA were reduced in IgAN patients treated with Nefecon vs placebo in Part A of the NefIgArd study at the 3-, 6- and 9-month mark after randomization. Levels of secretory IgA and fatty acid-binding protein, a gut permeability marker, were unchanged at these same time points. Reduction in IgA antibodies directed at dietary antigens supports a local disease-modifying effect for Nefecon via targeted action in the ileal GALT rather than modulation of gut permeability and antigen exclusion.
- Levels of three soluble biomarkers known for modulating B cell maturation, CD23, CD27, and CD30, were reduced in response to Nefecon 16 mg/day at the 3-, 6-, and 9-month post-randomization mark when compared to placebo responses. The degree of reduction in soluble CD23, CD27, and CD30 correlated with the magnitude of B-cell activating factor (BAFF) reduction at the same three study timepoints. Reduction in CD30 levels also correlated with the magnitude of IgA/IgG immune complex reduction at the 6- and 9-month timepoints. Together, these biomarker data add to the body of evidence supporting a disease-modification effect for Nefecon, including modulation of immune complex formation.
Additional analysis from the full Phase 3 NefIgArd trial
- Modeling analyses leveraging the two-year eGFR total slope from 352 patients enrolled in the Phase 3 trial were applied to the records of 192 real-world IgAN patients to evaluate the long-term clinical potential of Nefecon. Using published linear regression analysis, Nefecon was predicted to substantially delay progression to renal failure, with a modeled 62 % risk reduction vs placebo and a median delay to progression of 12.8 years.
The potential of setanaxib, a novel dual NOX inhibitor to modulate renal function and fibrosis was evaluated in a mouse model of Alport syndrome, a rare genetic disease characterized by fibrosis and progressive kidney damage. Setanaxib was evaluated alone or in combination with standard of care ramipril, an ACE inhibitor.
- Combined daily oral administration of setanaxib 60mg/kg and ramipril 10mg/kg resulted in a statistically significant reduction of urine albumin and albumin/creatinine ratio compared to vehicle alone after a 2-week and 4-week treatment duration.
- Histological analysis showed that this combination treatment decreased fibrosis and glomerular sclerosis.
- In silico and proteomics analyses demonstrated a reduction in both glomerular basement membrane proteins and collagen proteins in mice treated with both setanaxib and ramipril
All presentations are available on the Presentations and Publications page on the Calliditas’ corporate website.
For further information, please contact:
Åsa Hillsten, Head of Investor Relations & Sustanaibility, Calliditas
The information was sent for publication, through the agency of the contact persons set out above, on November 6, 2023 at 20:30 p.m. CET.