The National Institute for Health and Care Excellence (NICE) has recommended obinutuzumab (Gazyvaro, Roche) in combination with mycophenolate mofetil for treating adults with active class 3 or 4 lupus nephritis, with or without class 5 involvement. 

The decision will make the treatment available to approximately 12,000 people in England with this kidney-damaging autoimmune disorder, providing a therapy that substantially outperforms existing immunosuppressive treatments in restoring normal kidney function.

Lupus nephritis affects approximately 60% of people with systemic lupus erythematosus, with around 60,000 people living with the condition in England and Wales. The disease develops when the immune system attacks kidney cells, particularly in the glomeruli, causing inflammation that can lead to permanent scarring, kidney failure, and the need for dialysis or transplantation. The condition disproportionately affects women, as well as people from Asian, Black African, and Caribbean backgrounds.

Current treatment options for lupus nephritis include mycophenolate mofetil alone or in combination with belimumab, rituximab, or voclosporin, alongside corticosteroids.

How the Monoclonal Antibody Works

Obinutuzumab is a humanised type II anti-CD20 monoclonal antibody. Unlike type I anti-CD20 antibodies, this agent shows enhanced direct B-cell killing, causing more potent B-cell depletion. This mechanism results in a more rapid, deep, and sustained depletion of the peripheral B cells responsible for the autoimmune attacks on the kidney's filtering units (glomeruli).

Obinutuzumab is administered as 1000-mg intravenous infusions on day 1 and at weeks 2, 24, 26, and 52, with an optional additional dose at week 50, depending on the specific protocol. Treatment will be given alongside mycophenolate mofetil and corticosteroids as standard background therapy.

Evidence of Superior Renal Response

The endorsement was based on evidence from the ongoing international phase 3 REGENCY trial, which evaluated obinutuzumab plus mycophenolate mofetil vs mycophenolate mofetil alone (control arm) in 271 patients with class 3 or 4 lupus nephritis. At 76 weeks, 46.4% of patients in the obinutuzumab arm achieved complete renal response vs 33.1% in the control arm, representing a significant difference. Additionally, patients receiving obinutuzumab experienced significantly longer time to renal flare compared with those on standard treatment alone.

The trial also showed improved proteinuria response, with 55.5% of patients in the obinutuzumab group achieving this outcome compared with 41.9% in the control arm. 

These findings were supported by evidence from the phase 2 NOBILITY trial with 125 participants, which showed similar benefits. In that study, 35% of patients receiving obinutuzumab reached complete renal response at week 52, compared with 23% receiving placebo, with the treatment effect continuing through week 104.

“This combination treatment has been shown to significantly improve the quality of life for people living with lupus nephritis,” said Helen Knight, director of medicines evaluation at NICE. “The evidence shows obinutuzumab improves outcomes, helping to restore normal kidney function, prevent long-term organ damage and reduce the risk of kidney failure,” she added. 

Cost and Implementation

The treatment has a list price of £3312.00 per 1000-mg vial, although a confidential discount arrangement is in place. The committee noted that, as an intravenous therapy, obinutuzumab would reduce the number of daily oral immunosuppressive tablets some patients currently take and require less frequent dosing than some alternatives. The endorsement specifically covers the most severe forms of lupus nephritis, addressing an unmet medical need in this patient population.

NHS England will make the therapy available within 90 days of the final guidance publication.