A Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy on Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i)

The ASSIST study is a phase 2, double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of atrasentan vs. placebo in subjects with IgA nephropathy (IgAN) while on background standard of care therapy and an SGLT2 inhibitor (SGLT2i).

Start Date20 Jul 2023

Sponsor / Collaborator

Novartis Pharmaceuticals Canada, Inc.

CTR20212405

/ Active, not recruitingPhase 3

一项将Atrasentan用于治疗存在进行性肾功能丧失风险的IgA肾病患者的III期、随机、双盲、安慰剂对照研究（ALIGN研究）

[Translation] A phase III, randomized, double-blind, placebo-controlled study of atrasentan in patients with IgA nephropathy at risk of progressive renal function loss (ALIGN study)

比较Atrasentan与安慰剂在存在进行性肾功能丧失风险的IgAN受试者中的疗效和安全性；主要评估第24周时Atrasentan与安慰剂对蛋白尿水平的影响；次要评估评估Atrasentan与安慰剂从基线到第136周（随机治疗停止后4周）对估算肾小球滤过率(eGFR)变化的影响；比较Atrasentan与安慰剂之间的eGFR 2年期治疗变化率（从随机治疗第12周到第120周的eGFR斜率）；比较Atrasentan和安慰剂之间的eGFR总研究变化率（从基线到第136周的eGFR斜率）以及确定Atrasentan与安慰剂相比的安全性和耐受性特征。探索性评估与安慰剂相比，接受Atrasentan的受试者的生活质量(QOL)；Atrasentan的稳态药代动力学(PK)，为探索性暴露-反应分析提供支持；评估疾病生物标志物的变化以及其他安全性结局。

[Translation]

Compare the efficacy and safety of Atrasentan versus placebo in IgAN subjects at risk of progressive renal function loss; Primary assessment of the effect of Atrasentan versus placebo on proteinuria levels at Week 24; Secondary assessments to evaluate the effect of Atrasentan versus placebo on the change in estimated glomerular filtration rate (eGFR) from baseline to Week 136 (4 weeks after cessation of randomized treatment); Compare the 2-year treatment change rate of eGFR between Atrasentan and placebo (eGFR slope from Week 12 of randomized treatment to Week 120); Compare the overall study change rate of eGFR between Atrasentan and placebo (eGFR slope from baseline to Week 136) and determine the safety and tolerability profile of Atrasentan compared to placebo. Exploratory assessment of the quality of life (QOL) of subjects receiving Atrasentan compared to placebo; Steady-state pharmacokinetics (PK) of Atrasentan to support exploratory exposure-response analysis; Assess changes in disease biomarkers and other safety outcomes.

Start Date08 Jan 2022

Sponsor / Collaborator

Chinook Therapeutics U.S., Inc.

[+2]

JPRN-jRCT2071210028

/ RecruitingPhase 3IIT

A Phase 3, Randomized, Double-blind, Placebocontrolled Study of Atrasentan in Patients with IgA Nephropathy at Risk of Progressive Loss of Renal Function - The ALIGN Study

Start Date27 Sep 2021

Sponsor / Collaborator-

100 Clinical Results associated with Atrasentan

100 Translational Medicine associated with Atrasentan

100 Patents (Medical) associated with Atrasentan

520

Literatures (Medical) associated with Atrasentan

01 Apr 2025·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Pharmacoinformatics-based prediction of Checkpoint kinase-1 inhibitors from Momordica charantia Linn. for cancer

Article

Author: Ala, Chandu ; Kunjiappan, Selvaraj ; Murugesan, Sankaranarayanan ; Pandian, Sureshbabu Ram Kumar ; Haripriya, Subramanian ; Pavadai, Parasuraman ; Vijayalakshmi, Muniyandi

Checkpoint kinase 1 (Chk-1), a serine/threonine kinase family protein, is an emerging target in cancer research owing to its crucial role in cell cycle arrest. Therefore, we aimed to predict potential Chk-1 inhibitors from Momordica charantia Linn., using high-throughput molecular docking. We used a graph theoretical network approach to determine the target protein, Chk-1. Among 86 compounds identified from M. charantia L., five molecules such as α-spinasterol (-9.7 kcal × mol^-1), stigmasterol (-9.6 kcal × mol^-1), stigmasta-7,22,25-trienol (-9.5 kcal × mol^-1), campesterol (-9.5 kcal × mol^-1), and stigmasta-7,25-dien-3beta-ol (-9.5 kcal × mol^-1) and standard drug CCT245737 (-8.3 kcal × mol^-1) displayed highest binding affinity with Chk-1. Besides, pharmacokinetic studies have demonstrated the non-toxic and drug-like properties of these compounds. Furthermore, molecular dynamics (MD) simulation studies confirmed the strong intermolecular interactions and stability of the compounds with Chk-1. The estimation of binding free-energy derived from molecular docking was fully recognized by the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) produced from the MD simulation paths. Altogether, these five compounds may serve as effective inhibitors of Chk-1, thereby could be used to develop new medications for cancer treatment.

01 Mar 2025·Nature Reviews Nephrology

Endothelin receptor antagonists in chronic kidney disease

Review

Author: Liew, Adrian ; Kohan, Donald E ; Smeijer, J David ; Dhaun, Neeraj ; Heerspink, Hiddo J L ; Noronha, Irene L

Endothelin-1 is a potent vasoconstrictor that has diverse physiological functions in the kidney, including in the regulation of blood flow and glomerular filtration, electrolyte homeostasis and endothelial function. Overexpression of endothelin-1 contributes to the pathophysiology of both diabetic and non-diabetic chronic kidney disease (CKD). Selective endothelin receptor antagonists (ERAs) that target the endothelin A (ET_A) receptor have demonstrated benefits in animal models of kidney disease and in clinical trials. In patients with type 2 diabetes and CKD, the selective ET_A ERA, atrasentan, reduced albuminuria and kidney function decline. Concerns about the increased risks of fluid retention and heart failure with ERA use have led to the design of further trials to optimize dosing and patient selection. More recent studies have shown that the dual ET_A receptor and angiotensin receptor blocker, sparsentan, preserved kidney function with minimal fluid retention in patients with IgA nephropathy. Moreover, combined administration of a low dose of the ET_A-selective ERA, zibotentan, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, enhanced albuminuria reduction and mitigated fluid retention in patients with CKD. Notably, sparsentan and aprocitentan have received FDA approval for the treatment of IgA nephropathy and treatment-resistant hypertension, respectively. This Review describes our current understanding of the use of ERAs in patients with CKD to guide their optimal safe and effective use in clinical practice.

01 Mar 2025·DIABETOLOGIA

Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial

Article

Author: Kohan, Donald E ; Smeijer, J David ; Hou, Fan Fan ; Heerspink, Hiddo J L ; de Vries, Sieta T

AIMS/HYPOTHESIS:

In the Study Of diabetic Nephropathy with AtRasentan (SONAR), the endothelin receptor antagonist (ERA) atrasentan slowed progression of chronic kidney disease (CKD) in individuals with type 2 diabetes. Pre-clinical research suggests sex-based differences in the endothelin system might influence the efficacy and safety of atrasentan. We therefore assessed the effects of atrasentan in men and women participating in SONAR.

METHODS:

SONAR was a double-blind, placebo-controlled trial that compared atrasentan 0.75 mg/day with placebo in individuals with type 2 diabetes and CKD (eGFR 25-75 ml/min per 1.73 m², urine albumin/creatinine ratio [UACR] 300-5000 mg/g). The primary endpoint was defined as the time from randomisation to the first occurrence of a doubling in serum creatinine or kidney failure (eGFR <15 ml/min per 1.73 m², chronic dialysis, kidney transplantation or death from kidney failure). Hospitalisation for heart failure was the secondary endpoint. We performed Cox proportional hazards regression analyses to compare the treatment effect of atrasentan between male and female participants on the risk of the composite kidney outcome as well as hospitalisation for heart failure. Additionally, differences between male and female participants in atrasentan plasma exposure and eGFR change were assessed using, respectively, a t test and linear mixed effect model.

RESULTS:

Among 3668 randomised participants, 946 (25.8%) were female. Atrasentan significantly reduced the risk of the composite kidney outcome in female participants (HR 0.46 [95% CI 0.28, 0.76]) but not in male participants (HR 0.83 [95% CI 0.65, 1.05]; p value for interaction 0.032). Atrasentan compared with placebo reduced eGFR decline to a greater extent in female than in male participants (treatment effect difference between male vs female participants -0.99 ml/min per 1.73 m², p value for interaction=0.020). The RR for hospitalisation for heart failure with atrasentan vs placebo was 1.14 (95% CI 0.74, 1.76) in male participants and 1.88 (95% CI 0.98, 3.63) in female participants (p value for interaction=0.217). Female participants also had significantly higher atrasentan plasma exposure than male participants (geometric mean AUC 54.5 vs 42.6 ng/ml×h; p<0.001).

CONCLUSIONS/INTERPRETATION:

Atrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants. These data suggest that sex-specific dosing regimens may be considered to optimise ERA treatment.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01858532.

140

News (Medical) associated with Atrasentan

21 Mar 2025

·www.fiercepharma.com

Novartis snags FDA nod for Fabhalta in another kidney disease but leaves room for rival Apellis

Novartis' Fabhalta may be the first approved for complement 3 glomerulopathy, but it may not be the only one soon, as Apellis is also angling its Empaveli for the same kidney disease. Novartis’ kidney disease troika keeps marching forward.With a new FDA approval, the company’s Fabhalta has become the first treatment endorsed by the agency for the ultrarare kidney disease complement 3 glomerulopathy (C3G). But analysts spotted several shortfalls in the drug’s label, leaving more to be desired—and potential room for improvement for rival Apellis.Thursday’s approval clears Fabhalta to reduce excessive protein in the urine—a phenomenon called proteinuria—in adults with C3G.“This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients,” Carla Nester, M.D., at the University of Iowa, said in a statement.About one to two people per million worldwide are diagnosed with C3G each year, according to a Novartis estimate based on a 2020 study. The disease is marked by the buildup of C3 protein in the kidney glomeruli as a result of overactivation of the alternative complement pathway, triggering inflammation and kidney damage. Fabhalta works by inhibiting complement factor B, blocking activation of C3.Data from the phase 3 Appear-C3G trial initially showed that treatment with Fabhalta led to a statistically significant 35% relative reduction in proteinuria from baseline, as measured by 24-hour urine protein-to-creatinine ratio (UPCR), compared with placebo after six months. Nester was an investigator of the study.Then 12-month data found that Fabhalta’s proteinuria benefit was maintained after one year. And in patients who switched from placebo to Fabhalta, the magnitude of 24-hour UPCR improvement, at 31%, was similar to the outcome seen in the original Fabhalta group during a six-month testing period.C3G marks Fabhalta’s third U.S. indication, following its approval in paroxysmal nocturnal hemoglobinuria (PNH) in 2023 and IgA nephropathy (IgAN) last year.“It’s a molecule nephrologists already know, and we’re going to fully synergize our launch with the presence that we already have amongst these nephrologists,” Victor Bulto, president of Novartis U.S., said in an interview with Fierce Pharma ahead of the latest FDA approval. While Fabhalta is the first drug to enter the C3G field, it may soon have company. Apellis is also angling its Sobi-partnered C3 inhibitor Empaveli (pegcetacoplan) for a C3G nod. And by analysts’ observations, Apellis has better efficacy data.In the phase 3 Valiant trial, Empaveli led to a 68% relative reduction in proteinuria versus placebo after six months.Despite differences in trial design and baseline patient characteristics, analysts at Citi and William Blair view Empaveli as the winning C3G med between the two. And according to the team at William Blair, so too did Nester.Nester presented both trials’ results at the 2024 American Society of Nephrology Kidney Week conference in October. When asked about her expectation of commercial uptake for the two drugs, “she noted that physicians will be choosing based on efficacy, and pegcetacoplan has shown the best efficacy so would likely get the majority of patients,” William Blair analysts wrote in an October note.Novartis’ Bulto argued that C3G is a very heterogeneous disease, and the measurements of proteinuria can be highly variable, making cross-trial comparisons difficult.Rather than precise proteinuria numbers, doctors are really hoping to see stabilization of patients’ estimated glomerular filtration rate (eGFR), which is a key measurement of kidney function, Bulto argued.In Appear-C3G, Fabhalta appeared to confer eGFR stability through one year, compared with disease progression prior to treatment. However, the mean improvement of 1.3 mL/min/1.73m2 at six months was not statistically different from the 0.9 mL/min/1.73m2 deterioration seen with placebo.As the Fabhalta label now states, “there was no difference between arms in the proportion of patients with stable or improved eGFR compared to baseline at 6 months (90% in Fabhlata vs 89% in placebo).”That might be why the FDA’s approved indication for Fabhalta in C3G has specific language stating that it’s used “to reduce proteinuria.”In contrast, in Valiant, Empaveli showed a relative eGFR improvement of 6.3 mL/min/1.73m2 over placebo after six months. This represents an opportunity for Empaveli to earn a broader label without the proteinuria language, Evercore ISI analysts said in a Thursday note.However, to Bulto’s point of heterogeneity among C3G patients, Empaveli patients actually logged a 1.5 mL/min/1.73m2 eGFR decline from baseline in Valiant, although that was better than the 7.8 mL/min/1.73m2 drop seen in the placebo group. The Empaveli eGFR showing was not formally significant in Valiant thanks to the trial’s statistical design. Apellis’ study included adolescents. Novartis’ only enrolled adults, leading to an adult-only FDA label; Novartis has noted that the average age of diagnosis is around 23 years old. In addition, in the efficacy section, the FDA label specifies that Fabhalta’s profile has not been established in C3G patients following kidney transplant, whereas Empaveli has data in that population.“Overall, it looks to us like FDA label for [Novartis] includes specific language keeping the door open for [Apellis] to have a clearly differentiated label—on both breadth and efficacy,” the Evercore team said.There’s one potential advantage for Fabhalta, though—it’s an oral drug, while Empaveli is an injection.“We also hear from the patient community, if they can achieve that efficacy with an oral therapy, that's always a layer of preference as well,” Bulto said.Fabhalta is one of three meds that Novartis is developing against kidney diseases from different mechanisms of action. The company is also expecting an FDA decision on endothelin A receptor antagonist atrasentan in IgAN and is working on anti-APRIL antibody zigakibart.Commercially, Novartis is bringing “several products” and “several capabilities” in kidney diseases, Bulto noted. Apellis, in contrast, has one single asset here.

Clinical ResultPhase 3Drug Approval

21 Mar 2025

·endpts.com

FDA approves Novartis’ Fabhalta in another rare kidney disease

Novartis’ Fabhalta notched another FDA approval, this time in adults with an ultra-rare kidney disease called C3 glomerulopathy. Fabhalta is the first drug approved specifically to treat C3 glomerulopathy, or C3G, which is a progressive disease that damages the tiny filters in the kidney. In serious cases, the disease can eventually lead to kidney failure and lifelong dialysis. Fabhalta comes as a capsule taken twice a day. It’s also Fabhalta’s third approval — in late 2023, the drug got the green light for a rare blood disorder called paroxysmal nocturnal hemoglobinuria, and more recently it got an accelerated approval in a kidney disease called IgA nephropathy. The FDA’s decision in C3G was based on results from a Phase 3 study that showed that, alongside supportive care, treatment with Fabhalta led to a 35% reduction in proteinuria at 6 months compared to the placebo arm — meeting the primary endpoint of the study. Novartis in October also shared longer-term results that showed the proteinuria reduction was sustained through one year. In C3G, a part of the immune system known as the complement system is abnormally activated, and proteins build up in the small filters in the kidneys. Fabhalta blocks a protein that’s part of the complement system. The FDA had previously scheduled an advisory committee meeting to review Fabhalta in C3G, but canceled the meeting in February. “We had to produce, initially, six months of data, and then they [FDA] required 12 months of data. We submitted the 12 months of data, and the response was, we don’t deem it necessary anymore to have an adcomm. We don’t have more specifics than that,” Novartis’ US president Victor Bulto told Endpoints News in an interview ahead of the approval. When asked whether the cancellation was related to the new Trump administration, Bulto said that he didn’t know. “We only received a typical FDA communication saying that they didn’t deem it as necessary,” he said. Novartis has been building a suite of new kidney disease drugs, starting with Fabhalta. It’s also awaiting an FDA decision in the first half of the year on a drug called atrasentan in IgA nephropathy. And the pharma company is studying another drug called zigakibart, an anti-APRIL antibody, in Phase III for the same disease. Novartis acquired both drugs in its purchase of Chinook Therapeutics in 2023 for $3.2 billion.

Phase 3Clinical ResultDrug ApprovalAcquisitionAccelerated Approval

20 Mar 2025

·www.prnewswire.com

Novartis receives third FDA approval for oral Fabhalta® (iptacopan) - the first and only treatment approved in C3 glomerulopathy (C3G)

Phase III study showed sustained proteinuria reduction at one year with favorable safety1 Fabhalta is the only oral alternative complement pathway inhibitor thought to target the underlying cause of C3G1-3 C3G is an ultra-rare kidney disease typically diagnosed in young adults and often progresses to kidney failure2-4 Novartis continues to advance multiple kidney disease treatments with high unmet need, compounding capabilities and strengthening unique leadership presence EAST HANOVER, N.J., March 20, 2025 /PRNewswire/ -- Novartis today announced that oral Fabhalta® (iptacopan) has received U.S. Food and Drug Administration (FDA) approval for the treatment of adults with C3 glomerulopathy (C3G), to reduce proteinuria, making it the first and only treatment approved for this condition1-4. "C3G is a debilitating disease often affecting young people, impacting many aspects of their physical and emotional health, and our previous treatment options came with significant challenges," said Carla Nester, M.D., M.S.A., F.A.S.N., Professor of Pediatrics-Nephrology at the University of Iowa and Fabhalta APPEAR-C3G Study Co-Investigator. "This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients." Fabhalta is the only oral inhibitor of the alternative complement pathway to selectively target what is thought to be the underlying cause of the disease1-3. Before the approval of Fabhalta, patients had to rely on supportive care, broad immunosuppression, and symptom management5-6. "As someone whose family has suffered from C3G across multiple generations, it is difficult to fully express the physical and emotional challenges of living with this unrelenting disease," said Lindsey Fuller, C3G patient and Co-Leader of C3G Warriors. "To finally have an approved treatment – and one that can be taken orally – is something people with C3G have been waiting for. Today's approval brings new hope for me, my family, and so many others." C3G is a progressive and ultra-rare kidney disease that, until now, has had no approved treatments2-5. The average age of diagnosis is around 23 years old2. Prognosis is poor, with approximately half of people living with C3G progressing to kidney failure within 10 years of diagnosis, requiring lifelong dialysis and/or kidney transplantation2,7. People living with C3G may experience high levels of fatigue, mobility issues affecting everyday life activities, and mental health symptoms, including depression and anxiety8,9. Data supporting approval The pivotal Phase III APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G1,10. The study was comprised of a 6-month randomized, double-blind treatment period with Fabhalta compared to placebo in addition to supportive care, followed by an additional 6-month open-label treatment period where all participants received Fabhalta1,10. Treatment with Fabhalta resulted in clinically meaningful proteinuria reduction, which was seen as early as 14 days and sustained at 12 months1,10. Similarly, in the open-label period, proteinuria reduction was seen in participants who switched to Fabhalta1,10. Fabhalta demonstrated a favorable safety profile, with no new safety signals1. In patients with C3G, the most common adverse reactions (≥10%) with Fabhalta were nasopharyngitis and viral infections1. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires specific vaccinations1. Last month, Fabhalta received a positive CHMP Opinion in C3G by the European Medicines Agency (EMA)11. Regulatory reviews for this indication are ongoing in China and Japan. Transforming care in kidney disease "We extend our deepest gratitude to the patients and investigators who participated in our clinical trials, without whom this first FDA approval in C3G wouldn't have been possible," said Victor Bultó, President US, Novartis. "With this additional approval for Fabhalta – the second in kidney disease – we will leverage our established capabilities and expertise to bring this innovative treatment to patients in need as we work to help transform care for people living with kidney diseases." This is the third US approval for Fabhalta and its second within the Novartis kidney disease portfolio since August 2024, when Fabhalta was granted accelerated approval by the FDA for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Continued approval for this indication is contingent upon confirmatory evidence1. Fabhalta received its first FDA approval in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1. Discovered by Novartis, Fabhalta is also being studied in a broad range of other rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Studies are ongoing to evaluate the safety and efficacy profiles in these investigational indications. In addition to Fabhalta, Novartis is advancing the late-stage development of two additional IgAN therapies with highly differentiated mechanisms of action: atrasentan, an investigational oral endothelin A receptor antagonist that received FDA filing acceptance in Q2 2024 with a decision anticipated in H1 2025, and zigakibart, an investigational subcutaneously administered anti-APRIL monoclonal antibody that is currently in Phase III development. About APPEAR-C3G  APPEAR-C3G (NCT04817618) is a Phase III multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in patients with native kidney C3G1,12. The study comprises a 6-month double-blind period in which adult patients were randomized 1:1 to receive Fabhalta or placebo on top of supportive care, followed by a 6-month open-label period in which all patients receive Fabhalta (including those who were previously on placebo)1,12. The primary endpoint for the double-blind period was proteinuria reduction from baseline at 6 months for Fabhalta compared to placebo as measured by 24-hour urine protein-creatinine ratio (UPCR)1,12. In addition to the results from adult patients with C3G, enrollment is ongoing in a separate cohort of adolescent patients with C3G12. About C3 glomerulopathy (C3G) Each year, approximately 1-2 people per million worldwide are newly diagnosed with C3G, a form of membranoproliferative glomerulonephritis (MPGN)3. In C3G, overactivation of the alternative complement pathway – part of the immune system – causes deposits of C3 protein to build up in kidney glomeruli, which are a network of blood vessels that filter waste and remove extra fluids from the blood4,13. This triggers inflammation and glomerular damage that results in proteinuria (protein in urine), hematuria (blood in urine) and reduced kidney function4,14. Indication FABHALTA is a prescription medicine used to treat adults with a kidney disease called complement 3 glomerulopathy (C3G), to reduce protein in the urine (proteinuria). It is not known if FABHALTA is safe and effective in children with C3G. Important Safety Information FABHALTA is a medicine that affects part of the immune system and may lower one's ability to fight infections. FABHALTA increases the chance of getting serious infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. These serious infections may quickly become life-threatening or fatal if not recognized and treated early. Patients must complete or update vaccinations against Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks before the first dose of FABHALTA. If patients have not completed vaccinations and FABHALTA must be started right away, they should receive the required vaccinations as soon as possible. If patients have not been vaccinated and FABHALTA must be started right away, they should also receive antibiotics to take for as long as their health care provider tells them. If patients have been vaccinated against these bacteria in the past, they might need additional vaccinations before starting FABHALTA. Their health care provider will decide if they need additional vaccinations. Vaccines do not prevent all infections caused by encapsulated bacteria. Patients should call their health care provider or get emergency medical care right away if they have any of these signs and symptoms of a serious infection: fever with or without shivers or chills; fever with chest pain and cough; fever with high heart rate; headache and fever; confusion; clammy skin; fever and rash; fever with breathlessness or fast breathing; headache with nausea or vomiting; headache with stiff neck or stiff back; body aches with flu-like symptoms; or eyes sensitive to light. Health care providers will give their patients a Patient Safety Card about the risk of serious infections. Patients must carry it with them at all times during treatment and for 2 weeks after the last dose of FABHALTA. The risk of serious infections may continue for a few weeks after their last dose of FABHALTA. It is important for patients to show this card to any health care provider who treats them. This will help health care providers diagnose and treat patients quickly. FABHALTA is only available through a program called the FABHALTA Risk Evaluation and Mitigation Strategy (REMS). Before patients can take FABHALTA, their health care provider must enroll in the FABHALTA REMS program, counsel their patients about the risk of serious infections caused by certain bacteria, give their patients information about the symptoms of serious infections, make sure that their patients are vaccinated against serious infections caused by encapsulated bacteria and that they receive antibiotics if they need to start FABHALTA right away and are not up-to-date on vaccinations, as well as give patients a Patient Safety Card about the risk of serious infections. Patients should not take FABHALTA if they are allergic to FABHALTA or any of the ingredients in FABHALTA. Patients should not take FABHALTA if they have a serious infection caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae type b, when starting FABHALTA. Before taking FABHALTA, patients should tell their health care provider about all their medical conditions, including if they have an infection or fever, have liver problems, are pregnant or plan to become pregnant (it is not known if FABHALTA will harm an unborn baby), or are breastfeeding or plan to breastfeed as it is not known if FABHALTA passes into breast milk. Patients should not breastfeed during treatment and for 5 days after the final dose of FABHALTA. Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking FABHALTA with certain other medicines may affect the way FABHALTA works and may cause side effects. Patients should know the medicines they take and the vaccines they receive. Patients should keep a list of them to show their health care provider and pharmacist when they get a new medicine. FABHALTA may cause serious side effects, including those mentioned above as well as increased cholesterol and triglyceride (lipid) levels in the blood. Health care providers will do blood tests to check patients' cholesterol and triglycerides during treatment with FABHALTA. Health care providers may start patients on medicine to lower cholesterol if needed. The most common side effects of FABHALTA in adults include: headache; nasal congestion, runny nose, cough, sneezing, and sore throat (nasopharyngitis); diarrhea; pain in the stomach (abdomen); infections (bacterial and viral); nausea; and rash. Please see full Prescribing Information , including Boxed WARNING and Medication Guide . Novartis in kidney disease   Building on a 40-year legacy that began in transplant, Novartis is on a mission to empower breakthroughs and transform care in kidney health, starting with kidney conditions that have significant unmet need. Historically these conditions have had considerably less funding and research, leading to a treatment landscape largely focused on reactive or end-stage disease management, often with significant physical, emotional, and financial burdens. Our pipeline targets the underlying causes of disease, with an aim to protect kidney health and delay or prevent dialysis and/or transplantation. Our goal is to help patients get back to living life on their terms—whether at work, in school, or with loved ones, and by partnering with patients, advocates, clinicians, and policymakers we aim to raise awareness, accelerate diagnosis and get patients the right care, sooner.     Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "may," "could," "would," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis 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. Reimagine medicine with us: Visit us at and and connect with us on LinkedIn, LinkedIn US, Facebook, X/Twitter, X/Twitter US and Instagram. References FABHALTA prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corp; March 2025.  Martín B, Smith RJH. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. C3 Glomerulopathy. GeneReviews® [Internet]. Updated 2018. University of Washington, Seattle; 1993-2024. Available from: . Accessed February 2025.  Schena FP, Esposito P, Rossini M. A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease. Int J Mol Sci. 2020;21(2):525.  Caravaca-Fontán F, Lucientes L, Cavero T, Praga M. Update on C3 Glomerulopathy: A Complement-Mediated Disease. Nephron. 2020;144(6):272-280.  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(4S):S1-S276. doi:10.1016/j.kint.2021.05.021 National Kidney Foundation. Treatment for C3G. National Kidney Foundation. Available from: . Accessed February 2025. Smith RJH, Appel GB, Blom AM, et al. C3 Glomerulopathy – understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129-143. Feldman DL, Bomback A, Nester C. Voice of the patient: report of externally led patient-focused drug development meeting on Complement 3 Glomerulopathy (C3G). National Kidney Foundation. Published March 26, 2018. Available from: . Accessed February 2025. Lafayette R, Sidhu R, Proudfoot C, et al. Quality of life and fatigue burden in individuals living with Complement 3 Glomerulopathy – a real-world study. Nephrol Dial Transplant. 2024;39(Suppl 1). Smith RJ, Kavanagh D, Vivarelli M, et al. Efficacy and safety of iptacopan in patients with C3 glomerulopathy: 12-Month results from the Phase 3 APPEAR-C3G study. Presented at American Society of Nephrology (ASN) Kidney Week 2024; October 23-27, 2024; San Diego, CA. Novartis. Novartis oral Fabhalta® (iptacopan) receives positive CHMP opinion for the treatment of adults living with C3 glomerulopathy (C3G). Available from: . Accessed March 2025. ClinicalTrials.gov. Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy. (APPEAR-C3G). Available from: . Accessed February 2025. Ravindran A, Fervenza FC, Smith RJH, Sethi S. C3 Glomerulopathy Associated with Monoclonal Ig is a Distinct Subtype. Kidney Int. 2018;94(1):178-186. Medjeral-Thomas NR, O'Shaughnessy MM, O'Regan JA, et al. C3 Glomerulopathy: Clinicopathologic Features and Predictors of Outcome. Clin J Am Soc Nephrol. 2014;9(1):46-53. # # # SOURCE Novartis Pharmaceuticals Corporation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalPhase 3Clinical Result

100 Deals associated with Atrasentan

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KEGG	Wiki	ATC	Drug Bank
-	Atrasentan	-	DB06199

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Glomerulonephritis, IGA	NDA/BLA	United States	Novartis AG	18 Jul 2024
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	United States	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Japan	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Argentina	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Australia	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Belgium	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Brazil	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Canada	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Chile	AbbVie, Inc.	12 Jun 2013
Type 2 diabetes mellitus with established diabetic nephropathy	Phase 3	Czechia	AbbVie, Inc.	12 Jun 2013

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01858532 (SONAR, Pubmed \| Diabetologia)	Phase 3	Diabetes Mellitus, Type 2 \| Chronic Kidney Diseases	3,668	Atrasentan 0.75 mg/day	sqcwigxbsc(xktwexswxp) = Atrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants rwescabqom (scpjgejkrw )	Positive	11 Dec 2024
NCT04573478 (ALIGN, Pubmed) Manual	Phase 3	Glomerulonephritis, IGA	340	atrasentan	lvxukauptu(shhyanujvv) = odqjqgcumk ruwlefdqrf (ufntwvqvwa )	Positive	25 Oct 2024
				Placebo	lvxukauptu(shhyanujvv) = vnhznwzxye ruwlefdqrf (ufntwvqvwa )
NCT01858532 (SONAR, Pubmed \| Kidney Int)	Phase 3	Diabetes Mellitus, Type 2 \| Chronic Kidney Diseases estimated glomerular filtration rate \| urinary albumin-to-creatinine ratio	1,834	Atrasentan	sxomvnbutl(qpthfklcob) = wqxlfgazvt upwodegalj (cayznnebeh, 0.72 - 0.93)	Positive	01 Dec 2023
				Placebo	sxomvnbutl(qpthfklcob) = vsvmsaagym upwodegalj (cayznnebeh )
NCT04573478 (ALIGN , Corporate Publications) Manual	Phase 3	Glomerulonephritis, IGA	-	Atrasentan	mvsclpiepl(lkujhrkggp) = The study met its primary efficacy endpoint at the 36-week interim analysis, with atrasentan demonstrating superiority versus placebo with a clinically meaningful and highly statistically significant reduction in proteinuria (protein in urine) in patients with IgAN receiving supportive care (maximally tolerated and stable dose of a renin-angiotensin system [RAS] inhibitor). ahkwwfcmtp (owrstyolnl ) Met	Positive	30 Oct 2023
				Placebo
NCT01356849 (RADAR, ASN2022)	Phase 2	Type 2 diabetes mellitus with established diabetic nephropathy PCSK9	-	Atrasentan 0.75mg/d	wzjkmywppo(oqbcesabml) = fmcecwyjlc doafqfstkt (diezvgbkxb, -52.7 to 1.0)	Positive	05 Nov 2022
NCT04573920 (AFFINITY, ASN2022)	Phase 2	Glomerulonephritis, IGA	-	Atrasentan 0.75 mg	rstwaxfpsr(xjptvmypxq) = wlmulowgrm elwdscyyeb (wrfbcgpfun, 39.8 - 58.3)	Positive	03 Nov 2022
NCT04573920 (AFFINITY, Corporate Publications) Manual	Phase 2	Glomerulonephritis, IGA	20	Atrasentan	jvrbjoesam(egrzpnahbe) = ntccrfmwrl rnjqygvmso (szdjdfgcsg ) View more	Positive	01 Nov 2022
NCT01858532 (SONAR, Pubmed \| JACC Heart Fail)	Phase 3	Diabetes Mellitus, Type 2 \| Diabetic Nephropathies	5,107	Atrasentan 0.75 mg/day	jdfhcpxmxr(jktfesggff): HR = 1.39 (95% CI, 0.97 - 1.99), P-Value = 0.072	Positive	01 Jul 2022
				Placebo
NCT04573920 (AFFINITY, ERA2022)	Phase 2	Glomerulonephritis, IGA	17	Atrasentan 0.75 mg	ocwctrueid(qijicfsiua) = cshieqzhop ydkjshpdqk (dritgbguzb, 29.0 - 55.2)	Positive	03 May 2022
NCT01858532 (SONAR, Pubmed \| Clin J Am Soc Nephrol)	Phase 3	Heart Failure	3,668	Atrasentan	mmdmpoakkp(ytvijnnffn): hazard ratio = 1.39 (95% CI, 0.97 - 1.99) View more	-	01 Dec 2021
				Placebo

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