A Phase 3 study of Gazyva in lupus nephritis is expected to start next year.
The findings were presented at two meetings this month. The first presentation, “A Phase 2 Randomized, Controlled Study of Obinutuzumab with Mycophenolate and Corticosteroids in Proliferative Lupus Nephritis,” took place at the American Society of Nephrology’s Kidney Week 2019, in Washington.
The second presentation, “A Phase II Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Obinutuzumab or Placebo in Combination with Mycophenolate Mofetil in Patients with Active Class III or IV Lupus Nephritis,” occurred at the 2019 American College of Rheumatology and the Association of Rheumatology Professionals Annual Meeting, in Atlanta.
Gazyva — developed by Genentech (a subsidiary of Roche) and Biogen — is a monoclonal antibody that targets CD20, a protein found on the surface of certain healthy and malignant immune B-cells. By targeting CD20, the therapy is thought to induce cell destruction by the immune system.
While Gazyva is approved to treat blood cancers associated with malignant B-cells, its mechanism of action suggests that it could help prevent excessive inflammation in autoimmune diseases, such as systemic lupus erythematosus (SLE).
The multi-center, Roche-sponsored Phase 2 NOBILITY study (NCT02550652) was designed to evaluate whether adding Gazyva to standard treatment induced greater benefits than standard treatment alone in people with lupus nephritis, a common and serious kidney inflammation in SLE.
A total of 125 patients were randomly assigned to receive either Gazyva or a placebo, given intravenously (directly into the bloodstream) in combination with standard treatment — Genentech’s CellCept (mycophenolate mofetil) and corticosteroids — on days 1, 15, 168, and 182. Patients are being followed for up to two years.
The trial’s primary goal was to assess whether adding Gazyva to standard-of-care treatment induces complete kidney responses in a higher proportion of patients than a placebo, after one year of treatment.
Secondary goals include assessing overall response rates at one year, the levels of disease activity markers, and Gazyva’s safety and pharmacokinetics (uptake, distribution, and elimination in the body).
NOBILITY’s top-line data had shown that the study met its primary goal and several secondary goals.
Adding Gazyva to standard treatment led to a significantly higher proportion of complete and overall kidney response (partial or complete), as well as a decrease in other measures of disease activity, compared with a placebo. Also, no new adverse events were reported among patients receiving Gazyva.
These findings supported Gazyva’s breakthrough therapy designation by the U.S. Food and Drug Administration for the treatment of adults with lupus nephritis, which is intended to accelerate the therapy’s development, review, and approval.
Newly presented results showed that, at 18 months of treatment, rates of complete kidney response were increased from 34.9% to 40% between 12 and 18 months in the Gazyva group. In contrast, these rates were decreased in the placebo group (22.6% to 18%).
This means that adding Gazyva to standard treatment more than doubled the proportion of people achieving complete kidney response after 18 months.
Gazyva’s safety profile was consistent with that reported in previous trials, with no new adverse events at 18 months. Non-serious reactions to treatment administration were more common with Gazyva than with a placebo (15.9% vs. 9.7%). However, Gazyva was not associated with an increase in serious adverse events (24% vs. 29% in placebo group) or serious infections (6% vs. 18% in placebo group).
“We are very encouraged by the positive results from the NOBILITY study, which suggest that Gazyva may provide a clinically meaningful benefit for adults with proliferative lupus nephritis; a condition for which there is a strong need for more effective and targeted treatment options,” Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of global product development, said in a press release.
“These results support the continued development of Gazyva for people with lupus nephritis and underscore our longstanding commitment to pursue new treatment options that may benefit the lupus community,” Garraway added.
A replay of a webcast on NOBILITY’s findings is available here.
Forthcoming two-year data will allow further evaluation of longer-term safety and effectiveness of Gazyva in proliferative lupus nephritis.
“Obinutuzumab [Gazyva] could potentially result in a change in the lupus nephritis treatment paradigm if all goes well in future studies,” Richard A. Furie, MD, the trial’s principal investigator, said in another press release from the Lupus Research Alliance (LRA). Furie is also a member of Lupus Therapeutics’ Lupus Clinical Investigators Network, which is affiliated with the LRA.