RegulationPriority Review (United States), Breakthrough Therapy (United States), Accelerated Approval (United States), Orphan Drug (United States), Rare Pediatric Disease (United States), Orphan Drug (European Union), PRIME (European Union), Priority Review (China), Breakthrough Therapy (China), Orphan Drug (South Korea), Orphan Drug (Australia), Priority Review (Australia), Orphan Drug (Japan), Conditional marketing approval (China)

Structure/Sequence

Molecular FormulaC25H33ClN2O5

InChIKeyJUWBBUFSAGEROP-VVJLZRNGSA-N

CAS Registry2447007-60-3

Clinical Trials associated with Iptacopan

NCT06994845

/ Not yet recruitingPhase 3

A Single-arm, Multicenter, Phase III Study to Assess Efficacy, Pharmacokinetics, Safety and Tolerability of Iptacopan in Pediatric Patients of 2 to <18 Years of Age With Primary Immunoglobulin A Nephropathy (IgAN)

The study is an open-label, single arm, multicenter, Phase III study to determine proteinuria reduction, pharmacokinetics (PK), safety and tolerability (including CV surveillance) of iptacopan in primary immunoglobulin A nephropathy (IgAN) pediatric patients aged 2 to <18 years.

Start Date08 Dec 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT06934967

/ Not yet recruitingPhase 3

An Open-label, Single-arm, Multicenter, Phase 3 Study to Assess Pharmacokinetics, Safety and Tolerability of Iptacopan in Pediatric PNH Patients 2 to <18 Years of Age

The purpose of this open-label, single arm, multicenter, phase 3 study is to assess the pharmacokinetics of iptacopan in pediatric patients and to assess whether iptacopan is safe and well tolerated when used for the treatment of pediatric paroxysmal nocturnal hemoglobinuria (PNH) patients 2 to < 18 years of age.

Start Date28 Jul 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

NCT06931691

/ RecruitingNot Applicable

A Multi-center, Ambispective Cohort Study to Evaluate the Impact of Iptacopan on Disease Management, Treatment-Related Outcomes and Healthcare Resource Utilization for Adult Patients With Paroxysmal Nocturnal Hemoglobinuria in China

The implementation of new standards for the management of PNH and the use of iptacopan in patients with PNH are expected to change the treatment landscape and improve the overall prognosis of patients.
Based on these backgrounds, we plan to conduct a real-world study of iptacopan to further evaluate its impact on treatment-related outcomes, disease management, and healthcare resource utilization in Chinese patients with PNH.

Start Date10 Jun 2025

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

100 Clinical Results associated with Iptacopan

100 Translational Medicine associated with Iptacopan

100 Patents (Medical) associated with Iptacopan

103

Literatures (Medical) associated with Iptacopan

31 Dec 2025·Hematology

Severe hemolysis flare of refractory autoimmune hemolytic anemia with positive complement component C3d responsive to Iptacopan with cyclophosphamide and prednisone: a case report

Article

Author: He, Guangsheng ; Zhang, Yawen ; Gong, Yuemin

OBJECTIVES:

Autoimmune hemolytic anemia (AIHA) is characterized by autoimmune-mediated destruction of erythrocytes. Both AIHA and Evans syndrome are rare, manifesting a severe clinical course, high relapse rate, and potentially fatal outcomes. Refractory AIHA shows poor responsiveness to multiple treatment regimens, and there is still a lack of effective treatment regimens for serious hemolytic episodes.

METHODS:

Three refractory AIHA cases with a positive complement component C3d and hemolytic flare were treated with the oral factor B inhibitor ptacopan in conjunction with cyclophosphamide and prednisone.

RESULTS:

After treatment with iptacopan plus cyclophosphamide and prednisone, all three patients showed a rapid increase in Hb levels, a decrease in reticulocyte proportion, and a significant reduction in hemolysis manifestations (Lower LDH level and unconjugated bilirubin).

CONCLUSION:

Three refractory cases of AIHA showed good therapeutic efficacy after treatment with iptacopan combined with cyclophosphamide and prednisone. These cases provide a potentially effective treatment option for severe hemolytic episodes in refractory AIHA.

31 Dec 2025·Hematology

Successful switch from pegcetacoplan to iptacopan after repeated severe breakthrough hemolysis events – case report

Article

Author: Füreder, Wolfgang ; Reinisch, Andreas

OBJECTIVES:

A subset of paroxysmal nocturnal hemoglobinuria (PNH) patients develops clinically relevant extravascular hemolysis when treated with complement C5 inhibitors. These patients may benefit proximal complement inhibitors such as pegcetacoplan, danicopan or iptacopan. No studies comparing these substances are available. Breakthrough hemolysis (BTH) - defined by exacerbation of intravascular hemolysis despite complement inhibition - can be severe especially in patients treated with proximal complement inhibitors.

METHODS:

We report on a PNH patient who had suffered repeated episodes of severe BTH with acute renal failure during 1 year of treatment with pegcetacoplan. The patient was switched to iptacopan and followed also for 1 year.

RESULTS:

After switching to iptacopan, no further BTH occurred for the duration of 12 months follow up. The patient maintained stable hemoglobin and reticulocyte counts as well as lactate dehydrogenase (LDH) levels within the normal range.

DISCUSSION:

Despite dose escalation of pegcetacoplan, BTH recurred in our patient. Therefore, an alternative therapy was warranted. During iptacopan therapy - chosen due to patient preference -no further BTH occurred. However, more data from a larger number of patients are needed.

CONCLUSION:

A switch to iptacopan may be an option for pegcetacoplan treated patients who experience repeated BTH in spite of dose escalation.

01 Oct 2025·CTS-Clinical and Translational Science

Assessment of QT Interval Prolongation Using Concentration–QT Modeling for Iptacopan, an Oral Complement Factor B Inhibitor, in Healthy Individuals

Article

Author: Armas, Danielle ; McNamara, Elizabeth ; Kaetterer, Noemi ; Jarugula, Venkateswar ; Nidamarthy, Prasanna Kumar ; Schmouder, Robert ; Kulmatycki, Kenneth

ABSTRACT:

To assess cardiac and safety parameters of iptacopan (an oral, selective, reversible, small‐molecule factor B inhibitor), we conducted a phase I, single ascending dose (SAD), exposure–response study (A2107) instead of a traditional thorough QT study. Healthy participants were randomized 3:1 to receive a single, supratherapeutic, oral dose of iptacopan 400, 800, or 1200 mg, or placebo. A2107's primary objectives were to assess iptacopan's effect on Fridericia‐corrected QT interval (QTcF) in a pooled analysis with the SAD phase of the first‐in‐human X2101 study, and the safety and tolerability of supratherapeutic iptacopan doses in participants. Secondary objectives included pharmacokinetics, changes in selected electrocardiogram (ECG) parameters, and categorical changes to the QTcF, PR, and QRS intervals and heart rate (pooled analysis). Thirty‐two participants were randomized in A2107 and 56 in X2101; demographic data were similar across treatment groups. The estimated placebo‐adjusted change from Day 1 baseline in QTcF at the geometric mean maximum drug concentration was 1.61 (90% confidence intervals: 0.39 to 2.82), 1.26 (−0.42 to 2.94), and 0.84 (−1.54 to 3.22) ms for 400, 800, and 1200 mg doses, respectively. These primary results are consistent with no risk of QT prolongation at single, supratherapeutic, oral iptacopan doses; secondary ECG data support this conclusion. No deaths, serious adverse events (AEs), or AEs leading to study discontinuation were reported; iptacopan was overall well tolerated. A high systemic exposure of iptacopan was confirmed, allowing us to conclude that single, supratherapeutic, oral doses of iptacopan had no QTcF prolongation or proarrhythmic potential in healthy individuals.

232

News (Medical) associated with Iptacopan

20 Oct 2025

·investors.apellis.com

New One-Year Data Reinforcing the Robust and Sustained Efficacy of EMPAVELI® (pegcetacoplan) in C3G and Primary IC-MPGN to be Presented at ASN Kidney Week

Significant proteinuria reduction maintained at one year, regardless of immunosuppressant use or baseline proteinuria levels Complete proteinuria remission (UPCR ≤0.5 g/g) achieved in one-third of patients and sustained through one year Two indirect treatment comparisons indicate that EMPAVELI was superior to iptacopan in reducing proteinuria and achieving the composite renal endpoint in patients with C3G WALTHAM, Mass., Oct. 20, 2025 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) today announced new data from the open-label period of the Phase 3 VALIANT study that reinforce the robust and sustained efficacy of EMPAVELI® (pegcetacoplan), a C3 inhibitor, in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), rare and debilitating kidney diseases. Among seven EMPAVELI presentations at the upcoming American Society of Nephrology (ASN) Kidney Week, the new results build on previous data showing durable reductions in proteinuria and stable kidney function over one year with EMPAVELI. “These results further reinforce EMPAVELI’s ability to deliver meaningful, lasting benefits for patients with C3G and primary IC-MPGN, with consistent efficacy across patient groups,” said Peter Hillmen, M.B. Ch.B., Ph.D., chief medical advisor, rare disease, Apellis. “As the only approved treatment for C3G and primary IC-MPGN in patients 12 years and older, EMPAVELI has the potential to transform care for people living with these rare diseases, who have a high risk of kidney failure.” New One-Year Phase 3 VALIANT Data Reinforce EMPAVELI’s Robust and Sustained Treatment Effect Maintained proteinuria reduction regardless of immunosuppressant use or baseline proteinuria levels: Through one year, EMPAVELI sustained the significant 68% proteinuria reduction versus placebo (p<0.0001) achieved at Week 26, with consistent efficacy in patients who were or were not taking immunosuppressants and independent of baseline proteinuria levels. Complete proteinuria remission achieved in one-third of patients and sustained through one year: One-third of EMPAVELI-treated patients achieved complete proteinuria remission (urine protein-to-creatinine ratio [UPCR] ≤0.5 g/g) compared to 3% for placebo at week 26. These benefits were maintained through one year, and patients who switched from placebo experienced similar improvements. Additionally, EMPAVELI continued to stabilize kidney function as measured by estimated glomerular filtration rate (eGFR), a key measure of kidney function. EMPAVELI showed favorable safety and tolerability, consistent with its established profile. There were no new safety signals. EMPAVELI Was Superior to Iptacopan in Reducing Proteinuria Levels and Achieving the Composite Renal Endpoint in C3G Patients Two anchored indirect treatment comparisons (ITCs) were conducted using individual data from patients with C3G from the Phase 3 VALIANT study of EMPAVELI and published data from the Phase 3 APPEAR-C3G trial of iptacopan. The Bucher method, which preserves randomization, was used as the primary analysis with a matching-adjusted indirect comparison (MAIC), which adjusts for trial differences, as a supportive analysis. These analyses indicate that EMPAVELI was superior to iptacopan in lowering proteinuria levels and achieving the composite renal endpoint, which combines proteinuria reduction and stabilization of eGFR. A significantly greater proportion of EMPAVELI-treated patients achieved a UPCR reduction to less than 1 g/g, at least a 50% reduction in UPCR, and the composite renal endpoint. EMPAVELI was also numerically favored over iptacopan on improvement in eGFR. In the absence of a head-to-head study, anchored ITCs are valid and accepted methods for comparative effectiveness research used by health technology assessment bodies around the world.1,2 As with other indirect treatment comparisons, these studies may not adjust for all confounding factors due to differences inherent in study design and entry criteria. Key limitations include differences in the route of administration, treatment administration schedule, and dosing regimen. Presentation Details: Oral Presentation Pegcetacoplan for 52 weeks results in sustained proteinuria reduction to remission (≤0.5 g/g) and normalization (≤0.2 g/g): Phase 3 VALIANT trial - Carla M. Nester, MD, MSA, FASN - Glomerular Targeted Therapies: The New Era - Saturday, November 8 - 4:50-5:00 p.m. CT Poster Presentations Pegcetacoplan for 52 weeks maintains proteinuria reduction regardless of immunosuppressant use or nephrotic-range proteinuria at baseline: VALIANT subgroup analysis - Carla M. Nester, MD, MSA, FASN - Friday, November 7 - 10:00 am. - 12:00 p.m. CT - Poster FR-PO0836 Pegcetacoplan for 52 weeks maintains proteinuria reduction and eGFR stabilization in pediatric patients: Phase 3 VALIANT subgroup analysis - Larry A. Greenbaum, MD - Friday, November 7 - 10:00 a.m. - 12:00 p.m. CT - Poster FR-PO0693 Clinical efficacy of pegcetacoplan versus iptacopan in patients with C3 glomerulopathy: Indirect treatment comparisons - Bradley P Dixon, MD - Saturday, November 8 - 10:00 a.m. - 12:00 p.m. CT - Poster SA-PO0826 Human factors validation of a pegcetacoplan on-body injector demonstrates ease of use by adolescents with C3 glomerulopathy / primary immune-complex membranoproliferative glomerulonephritis - Eliyahu Khankin, MD - Friday, November 7 - 10:00 a.m. - 12:00 p.m. CT - Poster FR-PO0890 Pegcetacoplan for adolescents and adults with C3 glomerulopathy or primary immune-complex membranoproliferative glomerulonephritis: Enrollment status of the VALE extension - Eliyahu Khankin, MD - Thursday, November 6, 2025 - 10:00 a.m. to 12:00 p.m. CT - Poster INFO15-TH Pegcetacoplan for adults with high risk of delayed graft function: A phase 3, randomized, placebo-controlled trial - Eliyahu Khankin, MD - Thursday, November 6 - 10:00 a.m. to 12:00 p.m. CT - Poster INFO16-TH About the VALIANT Study The VALIANT Phase 3 study (NCT05067127) was a randomized, placebo-controlled, double-blinded, multi-center study that evaluated efficacy and safety of EMPAVELI® (pegcetacoplan) in 124 patients who were 12 years of age and older with C3G or primary IC-MPGN. It is the largest single trial conducted in these populations and the only study to include pediatric and adult patients, with native or post-transplant kidneys. Study participants were randomized to receive EMPAVELI or placebo twice weekly for 26 weeks. Following this 26-week randomized controlled period, patients were able to proceed to a 26-week open-label phase in which all patients received EMPAVELI. The primary endpoint of the study was the log transformed ratio of urine protein-to-creatinine ratio (UPCR) at Week 26 compared to baseline. About the Indirect Trial Comparisons (ITCs) A common placebo arm in both trials allowed two anchored indirect treatment comparisons (ITCs) to be performed using individual data from the Phase 3 VALIANT study of EMPAVELI and published data from the Phase 3 APPEAR-C3G trial of iptacopan among patients with C3G. The Bucher method, which preserves randomization, was used as the primary analysis and a matching-adjusted indirect comparison (MAIC), which adjusts for trial differences, was used as a supportive analysis. Outcomes assessed from the VALIANT study at week 26 and the Phase 3 APPEAR-C3G study at week 26 included urine protein to creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR) and composite renal endpoint (≥50% reduction from baseline in UPCR and ≤15% reduction in eGFR). As with other indirect treatment comparisons, matching may not adjust for all confounding factors due to differences inherent in study design and entry criteria. About EMPAVELI®/Aspaveli® (pegcetacoplan) EMPAVELI®/Aspaveli® (pegcetacoplan) is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. It is the first treatment approved in the United States for C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in patients 12 years of age and older, to reduce proteinuria. EMPAVELI is also approved for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other countries globally, and is under investigation for other rare diseases. About C3 Glomerulopathy (C3G) and Primary Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) C3G and primary IC-MPGN are rare and debilitating kidney diseases that can lead to kidney failure. Excessive C3 deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. Approximately 50% of people living with C3G and primary IC-MPGN suffer from kidney failure within five to 10 years of diagnosis, requiring a burdensome kidney transplant or lifelong dialysis therapy.3-5 Additionally, approximately 90% of patients who previously received a kidney transplant will experience disease recurrence.6 The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.7 U.S. Important Safety Information for EMPAVELI BOXED WARNING: SERIOUS INFECTIONS CAUSED BY ENCAPSULATED BACTERIA EMPAVELI, a complement inhibitor, increases the risk of serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, unless the risks of delaying therapy with EMPAVELI outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against encapsulated bacteria in patients receiving a complement inhibitor. Patients receiving EMPAVELI are at increased risk for invasive disease caused by encapsulated bacteria, even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious infections and evaluate immediately if infection is suspected. Because of the risk of serious infections caused by encapsulated bacteria, EMPAVELI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the EMPAVELI REMS. CONTRAINDICATIONS Hypersensitivity to pegcetacoplan or to any of the excipients For initiation in patients with unresolved serious infection caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B WARNINGS AND PRECAUTIONS Serious Infections Caused by Encapsulated Bacteria EMPAVELI, a complement inhibitor, increases a patient’s susceptibility to serious, life-threatening, or fatal infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis (caused by any serogroup, including non-groupable strains), and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. The initiation of EMPAVELI treatment is contraindicated in patients with unresolved serious infection caused by encapsulated bacteria. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of EMPAVELI, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy with EMPAVELI. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent EMPAVELI therapy is indicated in a patient who is not up to date with vaccines against encapsulated bacteria according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible. The benefits and risks of treatment with EMPAVELI, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by encapsulated bacteria. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Serious infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of EMPAVELI in patients who are undergoing treatment for serious infections. EMPAVELI is available only through a restricted program under a REMS. EMPAVELI REMS EMPAVELI is available only through a restricted program under a REMS called EMPAVELI REMS, because of the risk of serious infections caused by encapsulated bacteria. Notable requirements of the EMPAVELI REMS include the following: Under the EMPAVELI REMS, prescribers must enroll in the program. Prescribers must counsel patients about the risks, signs, and symptoms of serious infections caused by encapsulated bacteria, provide patients with the REMS educational materials, ensure patients are vaccinated against encapsulated bacteria at least 2 weeks prior to the first dose of EMPAVELI, prescribe antibacterial drug prophylaxis if patients’ vaccine status is not up to date and treatment must be started urgently, and provide instructions to always carry the Patient Safety Card both during treatment, as well as for 2 months following last dose of EMPAVELI. Pharmacies that dispense EMPAVELI must be certified in the EMPAVELI REMS and must verify prescribers are certified. Further information is available at www.empavelirems.com or 1-888-343-7073. Infusion-Related Reactions Systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria, pyrexia) have occurred in patients treated with EMPAVELI, which may resolve after treatment with antihistamines. Cases of anaphylaxis leading to treatment discontinuation have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue EMPAVELI infusion immediately, institute appropriate treatment, per standard of care, and monitor until signs and symptoms are resolved. Interference with Laboratory Tests There may be interference between silica reagents in coagulation panels and EMPAVELI that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, avoid the use of silica reagents in coagulation panels. ADVERSE REACTIONS Most common adverse reactions in adult and pediatric patients 12 years of age and older with C3G or primary IC-MPGN (incidence ≥10%) were infusion-site reactions, pyrexia, nasopharyngitis, influenza, cough, and nausea. USE IN SPECIFIC POPULATIONS Females of Reproductive Potential EMPAVELI may cause embryo-fetal harm when administered to pregnant women. Pregnancy testing is recommended for females of reproductive potential prior to treatment with EMPAVELI. Advise female patients of reproductive potential to use effective contraception during treatment with EMPAVELI and for 40 days after the last dose. Please see full Prescribing Information, including Boxed WARNING regarding serious infections caused by encapsulated bacteria, and Medication Guide. About the Apellis and Sobi Collaboration Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy. About Apellis Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company leading the way in complement science to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two C3-targeting medicines approved to treat four serious diseases. Breakthroughs for patients include the first-ever therapy for geographic atrophy, a leading cause of blindness, and the first treatment for patients 12 and older with C3G or primary IC-MPGN, two severe, rare kidney diseases. We believe we have only begun to unlock the potential of targeting C3 across many serious diseases. For more information, please visit http://apellis.com or follow us on LinkedIn and X. Apellis Forward-Looking Statement Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding the potential market opportunity of EMPAVELI for C3G and IC-MPGN. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether the data analyses of EMPAVELI for C3G and IC-MPGN in the presentations reported in this release indicate an effect that is greater than the actual positive effect ; and any other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 28, 2025 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Media: Tracy Vineis media@apellis.com 617.420.4839 Investors: Eva Stroynowski ir@apellis.com 617.938.6229 References 1. Guo JD, et al. BMJ Open. 2025;15(3):e091961 2. Tanaka, S et al. Value in Health. 2024;27(9):1179-1190. 3. Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143. 4. Servais A, et al. Kidney Int. 2012;82(4):454-464. 5. Zand L, et al. J Am Soc Nephrol. 2014;25(5):1110-1117. 6. Tarragón, B, et al. C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation. Clinical Journal of the American Society of Nephrology. August 2024; 19(8)1005-1015. doi: 10.2215/CJN.0000000000000474. 7. Data on file using literature consensus.

Clinical ResultPhase 3Drug Approval

17 Oct 2025

·www.globenewswire.com

Novartis Fabhalta® (iptacopan) meets Phase III primary endpoint, slows kidney function decline in patients with IgA nephropathy (IgAN)

In APPLAUSE-IgAN final analysis, Fabhalta demonstrated statistically significant, clinically meaningful improvement in estimated glomerular filtration rate (eGFR) slope vs. placebo over two years1 eGFR is key marker of kidney function; IgAN is progressive autoimmune kidney disease that leads to kidney failure in many patients1-3 Fabhalta is first and only approved complement inhibitor for adults with IgAN and has potential to delay disease progression4,5 Fabhalta received accelerated approval for reduction of proteinuria in adults with IgAN in US in 2024; data support 2026 submission for traditional FDA approval4,5 October 16, 2025 – Novartis today announced positive final results from APPLAUSE-IgAN, a Phase III study evaluating Fabhalta® (iptacopan) in adults living with IgA nephropathy (IgAN). Fabhalta, an oral alternative complement pathway inhibitor, demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of estimated glomerular filtration rate (eGFR) decline over two years1. “Progressive diseases such as IgAN present an urgent need for interventions that can ultimately improve kidney health. Many people with IgAN commonly experience fear and anxiety of disease progression,” said Ruchira Glaser, Development Unit Head, Cardiovascular, Renal & Metabolic, Novartis. “We are excited about today’s positive Phase III APPLAUSE-IgAN results showing slowed eGFR decline, which add to the growing evidence of Fabhalta as a targeted therapy to preserve long-term kidney function, giving hope to people living with this condition.” Novartis intends to use these data to support Fabhalta submissions in 2026. Alongside Fabhalta, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Vanrafia® (atrasentan) and investigational compound zigakibart. IgAN is a progressive autoimmune kidney disease with approximately 25 per million people newly diagnosed worldwide each year3. IgAN is highly debilitating as it leads to glomerular inflammation, proteinuria, and a gradual decline in eGFR2. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management2,6,7. Furthermore, people living with IgAN often face mental, social, and economic challenges2,8. Supportive care does not address the underlying causes of the disease and often fails to slow disease progression, reinforcing the need for more targeted therapies for IgAN3,9. In APPLAUSE-IgAN, Fabhalta was well tolerated with a favorable safety profile in line with previously reported data10. Full data from the APPLAUSE-IgAN final analysis will be presented at future medical meetings. Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway10. Discovered at Novartis, Fabhalta received US Food and Drug Administration (FDA) and European Commission (EC) approval in December 2023 and May 2024, respectively, for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). Fabhalta also received accelerated approval in the US in August 2024, and in China in September 2025, for the reduction of proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression (generally UPCR ≥1.5 g/g4,5,11,12. In 2025, Fabhalta received FDA and EC approval as well as approvals in China and Japan for the treatment of adults with C3 glomerulopathy (C3G), making it the first treatment approved for this condition13-15. Fabhalta is being studied in a broad range of rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN)16-18. Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications and support potential regulatory submissions16-18. APPLAUSE-IgAN (NCT04578834) is a Phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in 477 adult primary IgAN patients (main study population). Patients were randomized to Fabhalta or placebo, on top of supportive care (a stable dose of maximally-tolerated renin-angiotensin system (RAS) inhibitor therapy with or without a stable dose of SGLT2i)1. The two primary endpoints of the study for the interim and final analysis, respectively, are proteinuria reduction at 9 months as measured by UPCR, and the annualized total eGFR slope over 24 months10,18. During the final analysis, the following secondary endpoints were assessed: proportion of participants reaching UPCR 2 or maintenance dialysis or receipt of kidney transplant or death from kidney failure), and change from baseline to 9 months in the fatigue scale measured by the Functional Assessment Of Chronic Illness Therapy-Fatigue questionnaire19. The main study population enrolled patients with an eGFR ≥30 mL/min/1.73 m2 and UPCR ≥1 g/g at baseline10,18. In addition, a smaller cohort of patients with severe renal impairment (eGFR 20–30 mL/min/1.73 m2 at baseline) was also enrolled to provide additional information but not contributing to the main efficacy analyses10,19. Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. References Novartis. Data on file. Kwon CS, Daniele P, Forsythe A et al. A systematic literature review of the epidemiology, health-related quality of life impact, and economic burden of immunoglobulin a nephropathy. J Health Econ Outcomes Res 2021;8:36–45. Cheung C, Barratt J. The rapidly changing treatment landscape of IgA nephropathy. Semin Nephrol 2025;44:151573. Novartis Pharmaceuticals Corporation. Fabhalta prescribing information. 2023 (2025 update). Available at: https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf (accessed October 2025). Novartis Pharmaceuticals Corporation. Novartis receives FDA accelerated approval for Fabhalta® (iptacopan), the first and only complement inhibitor for the reduction of proteinuria in primary IgA nephropathy (IgAN) (2024). Available at: https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-fabhalta-iptacopan-first-and-only-complement-inhibitor-reduction-proteinuria-primary-iga-nephropathy-igan (accessed October 2025). Pitcher D, Braddon F, Hendry B et al. Long-term outcomes in IgAN. Clin J Am Soc Nephrol 2023;18:727–8. Mohd R, Mohammad Kazmin NE, Abdul Cader R, et al. Long-term outcome of immunoglobulin A (IgA) nephropathy: a single center experience. PLoS One. 2021;16:e0249592. National Kidney Foundation. The voice of the patient (2020). Available at: https://igan.org/wp-content/uploads/2021/01/VOP_IgAN_12-7-20__FNL.pdf (accessed October 2025). Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int 2021;100:S1–276. Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. N Engl J Med. 2025;392:531–543. Fabhalta®. EMA Summary of Product Characteristics. Novartis Europharm Limited (2024). Available at: https://www.ema.europa.eu/en/documents/product-information/fabhalta-epar-product-information_en.pdf (accessed October 2025). PHARMCUBE. Novartis expands indications for iptacopan, capmatinib in China (2025). Available at: Novartis Expands Indications for Iptacopan, Capmatinib in China PharmCube-News & Reports (accessed October 2025). Fineline Cube. Novartis’ fabhalta approved in China for C3 glomerulopathy (2025). Available at: Novartis' Fabhalta Approved in China for C3 Glomerulopathy - Insight, China's Pharmaceutical Industry (accessed October 2025). Pharma Japan. Novartis makes full foray into nephrology space with fabhalta: exec (2025). Available at: Novartis Makes Full Foray into Nephrology Space with Fabhalta: Exec | PHARMA JAPAN (accessed October 2025). Novartis. Press release. Novartis receives third FDA approval for oral Fabhalta® (iptacopan) – the first and only treatment approved in C3 glomerulopathy (C3G) (2025). Available at: https://www.novartis.com/news/media-releases/novartis-receives-third-fda-approval-oral-fabhalta-iptacopan-first-and-only-treatment-approved-c3-glomerulopathy-c3g (accessed October 2025). Clinicaltrials.gov. NCT04889430. Efficacy and Safety of Iptacopan (LNP023) in Adult Patients with Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy (APPELHUS). Available at: https://clinicaltrials.gov/study/NCT04889430 (accessed October 2025). Clinicaltrials.gov. NCT05755386. Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN (APPARENT). Available at: https://clinicaltrials.gov/study/NCT05755386 (accessed October 2025). Clinicaltrials.gov. NCT05268289. Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/ - V. Available at: https://clinicaltrials.gov/study/NCT05268289 (accessed October 2025). Rizk DV, Rovin BH, Zhang H et al. Targeting the alternative complement pathway with iptacopan to treat IgAN: design and rationale of the APPLAUSE-IgAN study. Kidney Int Rep 2023;8:968–79. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultDrug Approval

16 Oct 2025

·www.fiercepharma.com

Novartis advances IgAN efforts with phase 3 win for Fabhalta, plots FDA filing for full approval

While Novartis already has two approved IgA nephropathy medicines, a third is in late-stage testing. Novartis has spent considerable time and energy building its presence in the IgA nephropathy (IgAN) disease area, and now it can celebrate a key trial win for its first drug to gain an FDA approval in the indication.At the final analysis of the phase 3 Applause-IgAN trial, Novartis’ complement factor B inhibitor Fabhalta showed that it can slow kidney function decline and IgAN progression, the company said in an Oct. 16 release.The placebo-controlled trial measured patients’ kidney function by looking at their estimated glomerular filtration rate (eGFR) slopes over the span of two years. An eGFR blood test is a straightforward process to assess kidney functioning, and doing the tests over a period of time can show how patients’ conditions are progressing.Novartis plans to leverage the data for Fabhalta regulatory submissions next year, the company said in its release. The Swiss drugmaker didn’t share detailed results from the phase 3 trial but said they would be presented at future medical meetings.The final analysis showing follows Fabhalta’s prior win in the same study on a separate surrogate endpoint that measured the reduction in patients’ proteinuria (protein in the urine) at nine months versus placebo. That endpoint is an “increasingly recognized surrogate marker correlating with progression to kidney failure,” Novartis said at the time of the trial readout.Those data allowed the drug to secure an accelerated FDA approval in IgAN in April of last year. Now, Novartis believes it has the evidence to support a traditional FDA approval for the medicine.A debilitating autoimmune kidney disease, IgAN is diagnosed in about 25 people per million each year worldwide, according to Novartis. Many patients eventually progress to kidney failure. Supportive care and symptom management alone usually don't slow progression. Fabhalta won its original FDA approval in late 2023 as a treatment for the rare blood disease paroxysmal nocturnal hemoglobinuria. And, since its IgAN approval last year, the med picked up yet another approval in March as a treatment for complement 3 glomerulopathy.The medicine, which pulled down $201 million in the first half of 2025, forms part of Novartis’ ambitious positioning in IgAN. Besides Fabhalta, the company in April won an IgAN approval for Vanrafia, a medicine picked up in its $2.7 billion buyout of Chinook Therapeutics.In addition to those two medicines, the company’s investigational anti-APRIL antibody, zigakibart, is in phase 3 testing in IgAN.In this disease area, the Swiss drugmaker is going up against Travere Therapeutics and its Filspari, which is approved to slow kidney function decline in adults with primary IgAN who are at risk of disease progression. Calliditas Therapeutics’ Tarpeyo is also cleared to treat patients at risk of disease progression. All of the FDA approvals in IgAN so far are for oral medications.

Drug ApprovalPhase 3AcquisitionAccelerated Approval

100 Deals associated with Iptacopan

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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
C3 glomerulopathy	United States	Novartis Pharmaceuticals Corp.	20 Mar 2025
Glomerulonephritis, IGA	United States	Novartis Pharmaceuticals Corp.	07 Aug 2024
Hemoglobinuria, Paroxysmal	United States	Novartis Pharmaceuticals Corp.	05 Dec 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Complement Factor H Deficiency	NDA/BLA	European Union	Novartis Europharm Ltd.	27 Feb 2025
Myasthenia Gravis	Phase 3	United States	Novartis Pharma AG	31 Jul 2024
Myasthenia Gravis	Phase 3	United States	Novartis Pharmaceuticals Canada, Inc.	31 Jul 2024
Myasthenia Gravis	Phase 3	China	Novartis Pharmaceuticals Canada, Inc.	31 Jul 2024
Myasthenia Gravis	Phase 3	Japan	Novartis Pharma AG	31 Jul 2024
Myasthenia Gravis	Phase 3	Japan	Novartis Pharmaceuticals Canada, Inc.	31 Jul 2024
Myasthenia Gravis	Phase 3	Denmark	Novartis Pharma AG	31 Jul 2024
Myasthenia Gravis	Phase 3	Denmark	Novartis Pharmaceuticals Canada, Inc.	31 Jul 2024
Myasthenia Gravis	Phase 3	Germany	Novartis Pharma AG	31 Jul 2024
Myasthenia Gravis	Phase 3	Greece	Novartis Pharmaceuticals Canada, Inc.	31 Jul 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04578834 (APPLAUSE-IgAN, GlobeNewswire) Manual	Phase 3	Glomerulonephritis, IGA	477	Fabhalta	gvpibkswbw(whblctrkeq) = Fabhalta demonstrated statistically significant, clinically meaningful superiority compared to placebo in slowing IgAN progression measured by annualized total slope of eGFR decline over two years. erzzdusrog (nnaadyqpha ) Met View more	Positive	16 Oct 2025
				Placebo
NCT04820530 \| NCT04558918 (Pubmed \| Lancet Haematol)	Phase 3	Hemoglobinuria, Paroxysmal	-	Iptacopan 200 mg twice daily	visolgscop(prtlfoaxrq) = Clinical breakthrough haemolysis occurred in seven (7%) of 96 iptacopan-treated patients in APPLY-PNH (including both groups) and two (5%) of 40 in APPOINT-PNH, but it was generally mild or moderate with no iptacopan discontinuation krrbapwtzc (zsjjsbhrqf ) View more	-	01 Jun 2025
				Intravenous eculizumab or ravulizumab regimen
NCT04747613 (EHA2025) Manual	Phase 3	Hemoglobinuria, Paroxysmal	136	Iptacopan (APPLY-PHN in REP)	tiugleibiq(xosjnfwbls) = affwpvcfjd xlbdziorqi (phvqxkhawi ) View more	Positive	14 May 2025
				Iptacopan (APPOINT-PHN in REP)	tiugleibiq(xosjnfwbls) = knpbebbmgh xlbdziorqi (phvqxkhawi ) View more
NCT05630001 (APPULSE-PNH, EHA2025)	Phase 3	Hemoglobinuria, Paroxysmal	52	Iptacopan	kqbovzysof(naansumpjm) = kxwrpnuxbn mllgbjqdeq (mkbzmxzush, 1.74 - 2.29) View more	Positive	14 May 2025
PB2799 (EHA2025)	Not Applicable	Hemoglobinuria, Paroxysmal	43	Iptacopan	hooklkspox(abuzomubnj) = Two patients reported instances of missed iptacopan doses without notable clinical consequences gbwgeigfhw (vmtvawrrxh ) View more	Positive	14 May 2025
				Ravulizumab
PF1303 (EHA2025)	Phase 3	Hemoglobinuria, Paroxysmal	75	Iptacopan	rglzzfqnhl(hsyfmwzhlb) = bsfuaptvca tpibskkhbm (jaghgwqhku, 0.3) View more	Positive	14 May 2025
				Pegcetacoplan	rglzzfqnhl(hsyfmwzhlb) = dkxppdmlho tpibskkhbm (jaghgwqhku, 0.4) View more
PF671 (EHA2025)	Not Applicable	-	30	Iptacopan	rmavxocjxf(hdtlifnisw) = One bacterial infection was reported; a cystitis (Klebsiella) which did not lead to any iptacopan modification or discontinuation ktzdwwwtoy (kvsnmhucvn )	Positive	14 May 2025
				Iptacopan (Compassionate use)
NCT04817618 (APPEAR-C3G, FDA_CDER) Manual	Phase 3	C3 glomerulopathy	74	FABHALTA 200 mg	xpqimftfcm(klhxlqsnss) = cmoddrmhkw regrtihjbi (snmahqxhyc, 0.57 - 0.85) View more	Positive	20 Mar 2025
				Placebo	xpqimftfcm(klhxlqsnss) = cmhtgfsegx regrtihjbi (snmahqxhyc, 0.88 - 1.31) View more
NCT04820530 \| NCT04558918 (APPOINT-PNH, Pubmed) Manual	Phase 3	Hemoglobinuria, Paroxysmal	135	iptacopan (C5i-experienced patients)	omaehadinu(quggksdlzx) = hehawauoxn tbijukqfzc (cmkujbgcst ) View more	Positive	07 Jan 2025
				Placebo (C5i-experienced patients)	omaehadinu(quggksdlzx) = kdjhtvters tbijukqfzc (cmkujbgcst ) View more
ASH2024	Not Applicable	Hemoglobinuria, Paroxysmal	-	Iptacopan monotherapy 200 mg twice daily	zuykmaldqj(tbjjgzazgl) = fvdhllzshf asrhcewowi (figblscatz, 87.4) View more	-	09 Dec 2024
				Eculizumab	zuykmaldqj(tbjjgzazgl) = wapylexvfx asrhcewowi (figblscatz, 77.2) View more

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