Sayna Norouzi, MD, is an assistant professor of medicine, clinical nephrologist, and founder and director of the glomerular disease and polycystic kidney disease clinics at Loma Linda University Medical Center.

Sayna Norouzi, MD

Sayna Norouzi, MD, discusses Pegcetacoplan's Approval and the Shifting C3G Landscape.

Pegcetacoplan's Approval and Shifting C3G Landscape, with Sayna Norouzi, MD

After years of limited treatment options, the care landscape for 

 is undergoing a drastic transformation. Once defined by off-label therapies and uncertainty, the rare kidney disease obtained its second US Food and Drug Administration-approved treatment in July 2025 in the form of pegcetacoplan (Empaveli).

In March 2025, iptacopan (Fabhalta) became the first FDA-approved treatment for C3G, offering long-awaited hope to patients and providers. Now, with the approval of pegcetacoplan, 2 approved therapies are available—an unprecedented shift for a rare kidney disease that had long relied on off-label or trial-and-error approaches.

“For years and years, patients with C3G came to our clinics and we didn't have any specific FDA-approved medications for them,” Sayna Norouzi, MD, an assistant professor of medicine, clinical nephrologist, and founder and director of the glomerular disease and polycystic kidney disease clinics at Loma Linda University Medical Center, explained to 

. “We were treating them with medications that we were hoping would help control the disease, control the proteinuria, but we didn't have precise clinical trial results for any of those medications.”

Now, with 2 FDA-approved options, she says clinicians can have informed, hopeful discussions with their patients about the treatment options available to them. However, Norouzi cautions that this new era brings more than hope—it brings complexity.

“Having access to 2 really good medications as treatment options for our patients with C3G is exciting, but at the same time, it's bringing in a lot of responsibility on our side that we have to keep ourselves updated and navigate the treatment options for our patients in a really smart way to make sure that they are receiving the medication that is appropriate for the kind of disease that they're dealing with, for the situation that they are dealing with, because all patients are different,” Norouzi explained.

While these approvals mark major progress, she notes the need for long-term safety data, post-marketing experience, and future trials—including combination strategies—to optimize care.

Editors’ note: Norouzi has relevant disclosures with Calliditas, Novartis, Otsuka, and Boehringer Ingelheim.

Brooks A. FDA Approves Pegcetacoplan (Empaveli) for C3 Glomerulopathy, IC-MPGN. HCPLive. July 28, 2025. Accessed July 31, 2025. 

https://www.hcplive.com/view/fda-approves-pegcetacoplan-empaveli-for-c3-glomerulopathy-ic-mpgn

Campbell P. FDA Approves Oral Iptacopan (Fabhalta) as First C3 Glomerulopathy Therapy. HCPLive. March 20, 2025. Accessed July 31, 2025. 

https://www.hcplive.com/view/fda-approves-oral-iptacopan-fabhalta-as-first-c3-glomerulopathy-therapy

Videos

C3G treatment options expand with FDA approvals of pegcetacoplan and iptacopan, offering new hope for patient care.

Panelists discuss how the complexity of diagnosing C3 glomerulopathy (C3G), the need for long-term treatment options, and the importance of addressing unmet needs, including the psychological impact on patients and families, highlights the challenges and future directions in improving care for these individuals.

Treating the Whole Patient: Addressing the Broader Unmet Needs in C3G Management

Video content above is prompted by the following: 

Discussion on C3G Treatment and Challenges

The conversation highlighted various aspects of managing C3G, with an emphasis on treatment options, diagnosis, and unmet needs in patient care.

Diagnosing C3G can be complicated due to the need to differentiate between acquired and genetic forms of the disease.

Current treatment options focus on long-term therapy, but the uncertainty of how long treatment should continue remains a challenge.

C3G patients, especially young adults, face significant psychological challenges due to the uncertainty surrounding their disease and its impact on their future, such as career development, education, and family support.

Mental health and psychosocial support are critical. This includes addressing not just the disease itself but the broader emotional and social impacts of living with a chronic condition.

The pediatric population presents a key unmet need. Current studies (e.g., the VALIANT and APPEAR C3G studies) focus on patients aged 12 and older, but younger children with C3G (ages 7-9 years) also need treatment and safety data.

There is a need for the development of pediatric-friendly formulations of medications, such as liquid forms for those unable to swallow pills.

Early diagnosis is crucial. Physicians should strive to identify C3G in the general population earlier to prevent the progression to chronic kidney disease (CKD) and improve patient outcomes.

The ultimate goal is to prevent patients from needing dialysis by catching the disease early.

Future Directions and Precision Medicine:

While there has been significant progress in treatment options for C3G, the next phase of research should focus on identifying which patients will benefit most from specific therapies.

Precision medicine approaches will be critical in advancing the care for C3G and other glomerular diseases.

The discussion concluded with optimism about ongoing research and the potential to dramatically improve the outcomes for C3G patients through early intervention and personalized treatment strategies.

Panelists discuss how patient history, vaccination status, and risk of infection influence the decision to administer complement inhibitors, with some expressing caution in high-risk cases, particularly in pediatric populations with prior infections or low immunoglobulin levels.

Balancing Complement Inhibition and Infection Risk in C3G Treatment

Summary for Physicians on Use of Complement Inhibitors in High-Risk Patients:

Patients with nephrotic syndrome who experience significant protein loss, leading to very low IgG levels, are at an increased risk for infections. These patients may not be ideal candidates for complement inhibitors due to concerns about their ability to fight bacterial infections, particularly encapsulated organisms.

Early trial data, particularly from studies like 

, suggest that while complement inhibitors are used in posttransplant patients on immunosuppressive therapy, they did not significantly increase the risk of infections, especially when vaccinated and managed with prophylactic antibiotics.

Vaccination and prophylactic antibiotics (e.g., penicillin or macrolides) are essential to reduce infection risks when using complement inhibitors. It’s important to assess local infection resistance patterns (e.g., penicillin resistance rates) before initiating therapy.

Clinical trials, such as the APEX trial, excluded patients with a history of recurrent invasive infections caused by encapsulated organisms. However, in clinical practice, the timing of infections, vaccination status, and use of prophylactic antibiotics are important factors to consider.

A patient who has had a meningococcal infection but was not vaccinated may still be a candidate for complement inhibitor therapy if vaccinations are administered and prophylactic antibiotics are used.

In real-world settings, physicians may proceed with complement inhibitors in high-risk patients, provided that adequate precautions are taken, including vaccination, use of prophylactic antibiotics, and consultation with infectious disease specialists when necessary. This approach has been successful in managing patients safely over extended periods.

It’s crucial to address concerns from parents or caregivers, particularly in pediatric populations. Parents need reassurance regarding the safety of long-term use of complement inhibitors, especially in the context of infection risks.

After years of dormancy, the therapeutic pipeline for lupus nephritis is heating up and appears to offer a level of promise with the potential to start address the unmet need within the disease state.

In the last 5 years, the field has welcomed newly approved agents in belimumab and voclosporin, but the goal of achieving complete renal response in these patients remains out of reach for many. However, the therapeutic pipeline for lupus nephritis is heating up and appears to offer a level of promise with the potential to start addressing the unmet need within the disease state.

With multiple agents being examined in completed or ongoing clinical trial programs, nephrologists now look ahead with a renewed sense of optimism as options like obinutuzumab, anifrolumab, and ianalumab, which target B-cell depletion through anti-CD20, interferon alpha-beta receptor antagonism, and BAFF inhibition, respectively, as their mechanisms of action. Beyond these, several potential therapeutic options leveraging different mechanisms, including complement C3 inhibition, CAR-T, and more, are being investigated in phase 1 or 2 trials.

Further evidence of the therapeutic pipeline progress within lupus nephritis could be seen at the 

62nd European Renal Association (ERA 2025) Congress

, where multiple studies examined the impact of these therapies, including an analyses of the phase 2 NOBILITY trial of obinutuzumab. In all, ERA 2025 featured 24 presentations and 62 total abstracts focused on lupus nephritis, potential therapies, impact on quality of life, and more.

To learn more about how the field is navigating these recent updates and the anticipation around agents in development, the editorial team of HCPLive Nephrology sat down with leading subject matter expert Sayna Norouzi, MD, director of the Glomerular Disease Clinic, Polycystic Kidney Disease Clinic, and GlomCon Glomerular Disease Fellowship Program at Loma Linda University Medical Center, on the floor at ERA 2025.

Navigating Lupus Nephritis Pipeline Updates, with Sayna Norouzi, MD

Duarte-Garcia A. A New Era for the Treatment of Lupus. Rheumatology.org. Published May 22, 2023. Accessed June 9, 2025. 

http://rheumatology.org/patient-blog/a-new-era-for-the-treatment-of-lupus

DelveInsight Business Research, LLP . Lupus Nephritis Clinical Trial Pipeline Experiences Momentum: DelveInsight Estimates a Diverse Pipeline Comprising 30+ Companies Working in the Domain. Prnewswire.com. Published December 3, 2024. Accessed June 9, 2025. 

https://www.prnewswire.com/news-releases/lupus-nephritis-clinical-trial-pipeline-experiences-momentum-delveinsight-estimates-a-diverse-pipeline-comprising-30-companies-working-in-the-domain-302320381.html

Sayna Norouzi, MD, reflects on the recent progress in the therapeutic pipeline for lupus nephritis.

Sayna Norouzi, MD

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