NOBILITY, a phase 2 trial of 125 patients with lupus nephritis, showed that obinutuzumab plus standard of care led to clinically meaningful improvements in the percentage of patients with a complete renal response at weeks 52, 76 and 104, compared with placebo plus standard of care.3 Post-hoc analyses showed that compared with placebo plus standard of care, obinutuzumab plus standard of care delayed time to lupus nephritis flares and unfavorable kidney outcomes and reduced loss in estimated glomerular filtration rate (eGFR), a surrogate for kidney survival.
The REGENCY Trial
NOBILITY’s success justified the phase 3 REGENCY trial, Dr. Furie says. It included 271 patients with proliferative lupus nephritis. All study patients received the standard therapy, mycophenolate mofetil, plus a target dose of 7.5 mg/day of oral prednisone by week 12, and 5 mg/day by week 24. One-half got 1,000 mg of obinutuzumab on day 1, and at weeks 2, 24, 26 and 52, with or without a dose at week 50.
The study’s primary end point was a complete renal response at week 76, defined as a urine-protein-to-creatinine ratio (UPCR) lower than 0.5 (with protein and creatinine both measured in milligrams), an eGFR at least 85% of baseline value and no intercurrent events. Secondary end points included complete renal response with 7.5 mg/day or less of prednisone during weeks 64–76 and a UPCR less than 0.8, without intercurrent events.
More than 46% of patients who received obinutuzumab achieved the desired response, complete renal response, compared with 33.1% in the placebo group. The complete renal response rate was 42.7% for the patients in the obinutuzumab group, compared with 30.9% for patients who received standard care. The researchers saw UPCR less than 0.8 in 55% of patients in the obinutuzumab group vs. 41.9% of patients in the standard care group.
Patients in the obinutuzumab group had a higher frequency of serious adverse events related to infection, particularly COVID-19. “The REGENCY study was unfortunately the victim of the surprise attack by COVID,” says Dr. Furie. However, once the medical community gained experience with COVID and vaccines were developed, COVID-related adverse events decreased in frequency, he notes.
In March, Roche submitted a supplemental application for obinutuzumab, marketed as Gazyva/Zazyvaro, in lupus nephritis.
Prescribing Obinutuzumab
Vaccines are generally important for all autoimmune disease patients, but current politics and declining public support for vaccination make some patients in Dr. Furie’s practice hesitant to get vaccines that are important prior to starting obinutuzumab and other B cell-depleting drugs. “When you start immunosuppressive medicines, and I don’t care what their mechanism[s] of action are, they attack the immune system and make patients more susceptible [to these illnesses]. The bottom line is anybody going on a B cell depleter should be vaccinated,” says Dr. Furie. At a minimum, patients need influenza, pneumonia and COVID-19 vaccines, he adds.
