Richard Furie, MD, chief of the division of rheumatology with Norwell Health, discusses the results of a phase 2 trial examining obinutuzumab for lupus nephritis.
Results of a recent phase 2 trials presented at the 2019 American College of Rheumatology annual meeting in Atlanta, GA showcased obinutuzumab, a type II anti-CD20 monoclonal antibody, as a promising treatment for proliferative lupus nephritis.
The randomized, double-blind, placebo-controlled NOBILITY trial evaluated the efficacy and safety of obinutuzumab in combination with mycophenolate mofetil in 125 patients and found use increased complete and partial renal responses compared to placebo in the treatment of proliferative lupus nephritis.
Of the 125 patients in the study, 63 were randomized to receive obinutuzumab and 62 were randomized to the placebo arm. For inclusion in the study, patients needed to have biopsy-proven ISN/RPS 2003 Class 3 or 4 lupus nephritis and urine protein to creatinine(UPCR neater than 1 on a 24-hour collection. Investigators noted all patients in the study, regardless of group, received mycophenolate mofetil and corticosteroids.
The primary outcome measure of the study was complete renal response at week 52, which investigators defined as achieving UPCR less than 0.5, normal serum creatinine not increased by more than 15% from baseline, urine red blood cells less than 10 HPF without red blood cell casts. Secondary endpoint measures for the study included achievement of overall renal response(ORR), modified complete renal response without urinary sediment, and improvements in serologics markers of activity.
At 52 weeks, 34.9% of patients achieved the primary endpoint in the obinutuzumab group compared to 22.6% of the placebo group (12.3% delta; 80% CI 2.1% to 22.6%; P=0.115). In regard to ORR, investigators noted 55.6^ of patients receiving obinutuzumab and 35.5% of patients receiving placebo achieved ORR at week 52 (20.1% delta; 80% CI 8.9% to 31.3%; P=0.025).
Additionally, results indicated 91% of patients receiving obinutuzumab group had no detectable peripheral B cells as measured by high sensitivity flow cytometry. Investigators also noted significant improvements in anti-dsDNA titers and C3 and C4 levels were observed with obinutuzumab compared to placebo.
In regard to safety, obinutuzumab was not associated with an increased rate of serious adverse events (14.3% versus 21.0%) or serious infections (1.6% versus 12.9%) when compared with placebo.
For more on the results and implications of the NOBILITY trial, MD Magazine® caught up with Richard Furie, MD, chief of division of rheumatology with Norwell Health, at ACR 2019.
MD Mag: What did you learn from the phase 2 study examining obinutuzumab for lupus nephritis?
Furie: Well for lupus nephritis, if you poll doctors about what kind of effect size they would like to see. Obviously, you want to see a very high effect size, but the minimum effect size, I think most people will say will be in the 10 to 15% range. So, that means for everybody who receives drug, 1 out of 10 to 2 out of 10 will benefit. As I said before, the needs in lupus nephritis are huge.
I can't tell you how many of my patients have gone on to renal failure, to dialysis, and need for transplant. The biggest unmet need right now in lupus is lupus nephritis. So, I think the clinical implications of the outcome of this study are huge, because if we reproduce these results in phase 3, the paradigm for treating lupus nephritis may very well change and that would be to introduce obinutuzumab for patients with lupus nephritis specifically proliferative nephritis.