First-Ever Treatment for Lupus Nephritis Wins FDA Breakthrough Status

September 20, 2019

Roche announced this week that the U.S. Food and Drug Administration granted breakthrough therapy designation of obinutuzumab (Gazyva) for lupus nephritis, a major morbidity of systemic lupus erythematosus (SLE).

Roche announced this week that the U.S. Food and Drug Administration granted breakthrough therapy designation of obinutuzumab (Gazyva) for lupus nephritis, a major morbidity of systemic lupus erythematosus (SLE).

Obinutuzumab (Gazyva, Roche) is an FDA-approved treatment for chronic lymphocytic leukemia. It is a monoclonal antibody that works by blocking CD20, a protein found on the surface of B lymphocytes where chronic lymphocytic leukemia cells reside.

Finding an effective treatment for lupus nephritis has been challenging. Most existing treatments are associated with signficant adverse effects and have limited success. The objective is to design a treatment that can suppress autoimmune pathways that feed inflammation. B-cells have long been thought to offer an avenue of attack against overactive autoimmune pathways, but it's been a difficult road. With the exception of belimumab (Benlysta, GSK) approved for systemic lupus, other clinical trials have been launched and failed.

The FDA's decision is based the results of the phase two randomized, double-blind NOBILITY study that showed obinutuzumab, in combination with mycophenolate mofetil or mycophenolic acid and corticosteroids, led to more cases of a complete renal response in advanced lupus nephritis cases as compared to the group treated with standard care only.

The study, which included 126 people, met it's primary endpoint of complete renal response at 52 weeks and its secondary end point which included complete and partial renal response and improved serologic markers of disease activity. No new safety signals were reported.

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Narain S. and Furie R. writing in the September 2016 issue of Current Opinions in Rheumatology, wrote that investigators are currently pursuing at least 50 possible new treatments, or treatment targets, for systemic lupus. In their review, reported that few B-cell therapy trials have been successful. Other treatments, such as sifalimumab and anifrolumab, which target type 1 interferons, "have been efficacious albeit with an increase in incidence of Herpes zoster infections."

In a meta-analysis of existing studies on the calcineurin inhibitor tacrolimus for lupus nephritis, researchers writing in the March 2019 issue ofDrug Design, Development and Therapyfound that tacrolimus as induction therapy was effective and safe. The review included 13 clinical trials, of which 12 were randomized controlled trials. In clinical trials that compared combination treatment tacrolimus  and  glucocorticoids with cyclophosphamide and glucocorticoids, there were more cases of remission with the with the tacrolimus treatment group, but larger trials are needed to confirm these resuults.