Obinutuzumab Reduced Proteinuria, Improved eGFR in FSGS

Ladan Zand, MD

Credit: Mayo Clinic

Obinutuzumab was well-tolerated and significantly reduced proteinuria in patients with refractory primary focal segmental glomerulosclerosis (FSGS), which was associated with an improvement in estimated glomerular filtration rate (eGFR) and serum albumin.¹

These findings, from the first 12 months of an open-label phase 2 trial, were presented at The American Society of Nephrology (ASN) Kidney Week 2024, held October 23- 26 in San Diego, California, by Ladan Zand, MD, Associate Professor of Medicine at the Division of Nephrology and Hypertension at Mayo Clinic.

“Patients that truly have primary FSGS in adults about lose to 60% of patients may not respond appropriately to glucocorticoids that then need to treat with alternate therapy, and within that group there are patients that don’t respond to second- or third-line agents. These patients really have no other good therapeutic options available for them and they tend to have a progressive course and end up needing dialysis or transplant. Patients with primary FSGS tend to have a really high rate of recurrence post kidney transplantation so the options become really limited for these patients and how to go about treating them once they have failed therapies,” Zand told HCPLive during the meeting.

The trial enrolled 20 patients with FSGS with an average age of 43.5 years (standard deviation [SD], 17.5), 55% of which were male. Participants had an average systolic blood pressure (BP) of 132 mmHg (SD. 17.5), an average diastolic BP of 77.1 mmHg (SD, 9.5) and had disease refractory to an average of 2-3 therapies.¹

Participants received 2 doses of 1-gram obinutuzumab 2 weeks apart, at baseline and 6 months. The trial primarily evaluated change in proteinuria from baseline at 6 and 12 months. Secondary endpoints assessed complete (proteinuria <0.3g/d) or partial (50% reduction in proteinuria & proteinuria < 3.5 g/d) remission, & rates of serious adverse events (AEs).¹

Zand and colleagues found that participants treated with obinutuzumab had significant improvements in proteinuria, with average reductions from 10.7 g/d (interquartile range (IQR), 7.5-13.7) to 7.3 g/d (IQR, 4.0-10.3) at 6 months and 3.8 g/d (IQR, 1.5-8.6) after 12 months (P = .001). Overall, 8 patients (40%) reached complete remission or partial remission at 12 months and none had relapsed disease.¹

There were also improvements in eGFR from baseline (48 mL/min/1.73m2; IQR, 28-89) to 12 months (62 mL/min/1.73m2; IQR, 37-95; P = .04); serum albumin from baseline (2.5 g/dL; SD, 0.6) at 6 months (3.1 g/dL; SD, 0.8) and 12 months (3.5 g/dL; SD, 0.8; P <.001); total cholesterol from baseline (285 mg/dL; SD, 120) at 6 months (277 mg/dL; SD, 132) and 12 months (213 mg/dL; SD, 49; P = .002); LDL cholesterol from baseline (194 mg/dL; SD, 122) at 6 months (175 mg/dL; SD, 148) and 12 months (122 mg/dL; SD, 40; P = .008); and B-cell counts from baseline (160 cells/uL; IQR, 75-251) at 6 months (0 cells/uL; IQR, 0-1) and 12 months (0 cells/uL; IQR, 0-0; P <.001). There was no significant improvement in serum creatinine from baseline to 12 months.¹

Three serious AEs unrelated to treatment did occur during the trial, these were suicidal ideation and pseudo-seizures in 1 participant and the development of follicular lymphoma in another. Common AEs included infusion-related reactions in 7 patients, none of which resulted in therapy discontinuation, and 7 infections, none of which required hospitalization.¹

“We were able to see an improvement in their GFR. A lot of time we don’t anticipate GFR to get better with treatment especially when they have failed other therapies. Perhaps we can expect to slow it down but to see that GFR improved was a really nice change to see, and also [to see] how many patients responded to the therapy within that 1 year,” Zand said.

Obinutuzumab is a type 2 anti-CD20 antibody marketed under the name Gazyva and currently approved for treating patients with chronic lymphocytic leukemia and follicular lymphoma.²

REFERENCES
1. Zand L, Greene EL, Cheungpasitporn W, et al. Single-Center, Phase 2, Open-Label Trial Evaluating the Efficacy and Safety of Obinutuzumab in Treatment of Immunosuppression-Resistant Primary FSGS, or Contraindication to High-Dose Corticosteroids. Presented at: ASN Kidney Week 2024.

2. Gazyva FDA Approval History. Webpage. Drugs.com. https://www.drugs.com/history/gazyva.html