IgA Nephropathy Clinical Trial Monitor — Complement, BAFF & Endothelin Programs 2026

The IgA nephropathy trial landscape in 2026

IgA nephropathy (IgAN) has undergone an extraordinary therapeutic transformation. Before 2021, patients had no approved disease-modifying therapy — only supportive care with renin-angiotensin system (RAS) inhibitors and occasional immunosuppression. By 2024, three targeted therapies were approved, each acting through a different mechanism. The pace of this transformation is nearly unprecedented in nephrology.

The commercial proof of concept is clear: IgAN is now a high-value target with demonstrated regulatory pathways. With 21+ active trials and multiple Phase 3 programs competing across complement, BAFF/APRIL, endothelin, and anti-CD38 mechanisms, the IgAN landscape has become one of the most densely competed in nephrology drug development. Novartis alone has four active IgAN programs, reflecting the strategic value of a leading position in the space.

Three approved therapies reshaped the IgAN field

Tarpeyo (budesonide ER, Calliditas Therapeutics)

Tarpeyo is a targeted-release formulation of the corticosteroid budesonide designed to reach peak levels in the distal ileum, where IgA-producing B cells are concentrated. It received FDA accelerated approval in December 2021 based on proteinuria reduction, with full approval following in August 2023 after the NEFIGAN trial demonstrated kidney function preservation. Calliditas is running an extended study (NCT06712407) to generate additional long-term data.

Filspari (sparsentan, Travere Therapeutics)

Filspari is the first-in-class dual endothelin type A receptor (ETA) and angiotensin II type 1 receptor (AT1) antagonist approved for IgAN. By blocking both the endothelin and renin-angiotensin pathways simultaneously, sparsentan provides greater proteinuria reduction than RAS inhibition alone. Full FDA approval was granted in February 2024 following positive PROTECT trial data. Travere's lifecycle management and competitor monitoring programs are active.

Fabhalta (iptacopan, Novartis)

Fabhalta is the first complement inhibitor approved for IgAN — a complement factor B (FB) inhibitor that blocks the alternative complement pathway. Novartis received FDA approval in August 2024 based on the APPLAUSE-IgAN Phase 3 trial demonstrating significant proteinuria reduction and kidney function preservation. Multiple OLE studies (NCT04557462) are ongoing, and Novartis is studying iptacopan in additional kidney indications.

Complement, BAFF/APRIL, and endothelin: the three dominant pathways

Complement pathway inhibition

Following iptacopan's approval, complement remains an active development target in IgAN:

• MASP-2 inhibitors (lectin pathway) are in early clinical development
• C3 and C5 inhibitors being evaluated in IgAN subpopulations with complement deposition
• Iptacopan OLE studies generating long-term safety and durability data critical for prescribing confidence

BAFF/APRIL pathway: reducing pathogenic IgA production at the source

BAFF and APRIL are cytokines that drive the production of galactose-deficient IgA1 (Gd-IgA1) — the pathogenic immunoglobulin central to IgAN. Two major programs target this axis:

• Zigakibart (Novartis): Anti-APRIL monoclonal antibody in Phase 3 OLE (NCT06858319). APRIL is a key driver of IgA class switching; blocking it directly reduces Gd-IgA1 production.
• Sefaxersen (Roche): A subcutaneously administered siRNA that silences hepatic expression of APRIL protein (NCT05797610). This RNAi approach provides sustained APRIL suppression from a single injection. Phase 3 OCTOBER trial ongoing.

Both programs target the same APRIL protein but with different modalities (antibody vs. siRNA), representing a direct head-to-head competition at the mechanism level between Novartis and Roche.

Endothelin and RAS: well-validated renoprotective pathway

Sparsentan (Filspari) has validated the dual ETA/AT1 blockade approach. Post-approval real-world studies are examining long-term renal outcomes, adherence, and use in combination with newer targeted agents. The endothelin pathway may also have relevance in other kidney diseases (FSGS), expanding its clinical importance beyond IgAN.

Anti-CD38: targeting long-lived plasma cells

Takeda's mezagitamab (anti-CD38) targets plasma cells that produce pathogenic IgA. CD38 is expressed on long-lived plasma cells in the bone marrow that are not addressed by APRIL/BAFF inhibition, potentially offering additive or complementary benefit. Takeda's Phase 3 study (NCT06963827) is a key trial to watch, given CD38 antibodies' established success in multiple myeloma and emerging roles in autoimmune disease.

Phase 3 spotlight: key IgA nephropathy trials

NCT ID	Sponsor	Drug / Intervention	Phase	Mechanism	Status
NCT06858319	Novartis	Zigakibart — anti-APRIL antibody OLE	Phase 3 OLE	APRIL inhibition	Active
NCT04557462	Novartis	Iptacopan (Fabhalta) OLE	Phase 3 OLE	Complement factor B inhibition	Active
NCT05797610	Roche / Genentech	Sefaxersen — APRIL-targeting siRNA (OCTOBER trial)	Phase 3	APRIL siRNA	Recruiting
NCT06963827	Takeda	Mezagitamab — anti-CD38 antibody	Phase 3	Anti-CD38 / plasma cell depletion	Recruiting
NCT06712407	Calliditas Therapeutics	Tarpeyo (budesonide ER) — extended study	Phase 3/4	Targeted corticosteroid / IgA production	Active
NCT07390123	Haisco Pharmaceutical	HSK39297 — Phase 3	Phase 3	TBD	Recruiting

Top sponsors in IgA nephropathy

• Novartis — Dominant portfolio with 4 active IgAN programs: iptacopan (Fabhalta, approved), iptacopan OLE, zigakibart Phase 3 OLE, and additional complement programs. Largest IgAN sponsor by far.
• Roche / Genentech — Sefaxersen siRNA Phase 3 (OCTOBER trial); direct APRIL-axis competition with Novartis's zigakibart using a differentiated RNA modality.
• Takeda — Mezagitamab Phase 3 targeting CD38+ plasma cells; distinct mechanism with potential for combination with complement/APRIL inhibitors.
• Calliditas Therapeutics — First approved IgAN therapy (Tarpeyo); ongoing extended studies and lifecycle management programs. European market through Stada partnership.
• Travere Therapeutics — Filspari (sparsentan) fully approved 2024; post-approval real-world studies and potential label expansion work.

Monitoring IgAN trials for nephrology BD teams

IgAN's rapid evolution — three approvals in three years, multiple Phase 3 programs still running, and at least two distinct multi-billion-dollar mechanism races underway — makes it one of the most commercially dynamic indications in nephrology. Key intelligence events to track:

• Novartis vs. Roche in APRIL inhibition: Zigakibart (antibody) vs. sefaxersen (siRNA) target the same protein via different modalities. Phase 3 data timing and enrollment updates are critical competitive signals for any company with an IgAN BD position.
• Takeda mezagitamab Phase 3 enrollment: Anti-CD38 in IgAN is a new frontier — positive Phase 3 data would open a new mechanism category and likely trigger partnership activity.
• Iptacopan OLE durability data: Long-term complement inhibition data from Novartis will shape physician confidence in the complement class and affect the market entry strategy for competitive programs.
• New trial registrations: The IgAN pipeline is still expanding. New early-phase programs in combination therapy (APRIL inhibitor + complement inhibitor) represent the next competitive wave.
• Haisco and other emerging biotech entrants: HSK39297 Phase 3 registration (NCT07390123) signals global competitive expansion; monitoring non-Western biotech entries is important for global BD strategy.

DataLookout monitors all IgAN trials on ClinicalTrials.gov daily, delivering field-level change alerts on sponsor, status, enrollment, and protocol changes.

Related nephrology and immunology trial monitors

• Chronic kidney disease clinical trials — broader CKD pipeline including SGLT2i programs and anti-fibrotic agents
• Lupus clinical trials — overlapping complement and BAFF/APRIL biology; lupus nephritis programs share mechanisms with IgAN
• Myasthenia gravis clinical trials — anti-FcRn programs (shared mechanism class with IgAN anti-IgG approaches)