Clinical Trial Shows Promise in Treating Lupus Nephritis With Existing Drug Belimumab

Update: It was announced on December 18, 2020 that the US Food and Drug Administration (FDA) has expanded the indication for belimumab (Benlysta) to adults with active lupus nephritis who are receiving standard therapy.

Despite existing treatments and advancements in medicine, 10–30% of people with lupus nephritis reach end-phase kidney failure. As this condition can be fatal, patients with lupus nephritis are in need of more treatment options.

The positive results of a phase 3 clinical trial led by Richard Furie, MD, chief of rheumatology at Northwell Health, indicate that the drug belimumab (brand name Benlysta) helps manage lupus nephritis. If approved by the Food and Drug Administration (FDA), belimumab would be the first drug approved by the FDA to treat lupus nephritis.

What Is Lupus Nephritis?

Lupus nephritis is triggered by systemic lupus erythematosus (SLE), the most common form of lupus. Lupus is an inflammatory autoimmune disease that causes the immune system to mistakenly attack the body’s healthy tissues. It can affect the joints, skin, kidneys, blood cells, brain, heart and lungs. Lupus nephritis occurs when a person with SLE has kidney involvement. Between 25 to 60% of people with SLE develop lupus nephritis.

Some common symptoms of lupus nephritis include:

Swelling of the legs, ankles and feet
Weight gain
High blood pressure
Dark urine
Foamy, frothy urine
The need to urinate during the night

Like with many chronic illnesses, symptoms of lupus nephritis can be debilitating for those who live with the condition. Diane Jobin-Gilroy, a participant in the phase 3 clinical trial for belimumab, explained to The Mighty how her lupus nephritis symptoms affected her life. She said:

I was very sick where I had trouble walking, even turning taps for water for the shower and stuff like that. I couldn’t do anything. It was just debilitating. I already knew I had lupus and needed to go for help. I felt like this could not be a life.

According to a 2012 study, 10 to 30% of people with lupus nephritis progress to end-stage renal failure (ESRD), also known as kidney failure. Lupus patients with ESRD have a 26-fold increase for risk of death. There are currently no medication treatment options that target lupus nephritis directly.

What Is Belimumab?

Belimumab, also known by its brand name Benlysta, is a biologic drug, which means it is made in part using living organisms. Belimumab was previously approved by the FDA in 2011 to treat patients with active, autoantibody-positive lupus who are also on other standard therapies for the condition. Autoantibodies are a type of antibody produced in the immune system that attack healthy proteins.

In initial clinical trials to approve the drug for lupus patients, researchers identified that in combination with a patient’s other treatments, belimumab reduced lupus symptoms in a significant number of people. For example, in one phase 3 clinical trial, the response rate for patients taking 10 mg of belimumab was 58% compared to 44% who received a placebo.

The primary side effects reported during belimumab trials included nausea, diarrhea, fever, insomnia, migraine, and depression, among others.

Belimumab for Lupus Nephritis

To continue building on the success of its early clinical trials, Dr. Furie said one of the reasons belimumab could be helpful in managing lupus nephritis is because it could be safer than some medications already used to manage the condition. The research stemmed from the Feinstein Institutes for Medical Research, the science arm of Northwell Health.

“When the FDA approved belimumab in March 2011, it has a very good safety profile,” Furie said. “That seems to extend to this particular study too. That’s important because patients with lupus nephritis get steroids, they get mycophenolate. We do see problems. We do see infections and toxicity with steroids.”

The most recent phase 3 clinical trial (nicknamed BLISS-LN) for belimumab was conducted internationally and included 448 patients with active lupus nephritis. Patients already on a standard therapy for lupus enrolled in the trial were given belimumab or a placebo. Furie explained why patients were given belimumab as an “add-on” treatment:

The way that the study was designed was to use belimumab as add-on therapy. In fact, that’s how all our trials are done because you do not want to deprive the patient of the standard of care. In this particular therapy, the design was unique because it allowed patients to be on mycophenolate as a background therapy or cyclophosphamide.

Most studies for lupus nephritis (and many clinical trials in general) have six- or 12-month endpoints. The current clinical trial followed patients for two years, providing better data on long-term use and effectiveness. Roughly 90% of people included in the trial were women, which is representative of the ratio of lupus, which occurs at a ratio of 9:1 in between women and men.

What the Study Found

In this study, belimumab combined with standard therapy reduced the risk of worsening kidney function by almost 50% compared with standard therapy alone (the placebo). After 24 months, 43% of patients who received belimumab achieved primary efficacy renal response in comparison to 32% of those who received placebo. Furie also said patients had a reduced risk of flares.

Before enrolling in this trial, photographer and Lyft driver Elijah White, who has lupus nephritis, said he struggled with depression. White told The Mighty he enrolled in the trial to see if belimumab could help with his lupus symptoms, which included arthritis. “I just wanted to see if anything would help the situation because I did not want it to get worse.”

White started to feel relief around two months after receiving drug therapy, but he does not know whether he was given belimumab or the placebo. Regardless of whether they received the active drug or placebo, participants were offered the option to continue belimumab for free after the conclusion of the two-year trial. White accepted.

“I felt that it was helping. I didn’t have any side effects,” White said. “It helps with the nephritis and helps me overall because my other organs are actually functioning normally as well.”

Like White, Jobin-Gilroy joined the trial because she wanted to see if there was a medication that could help her. Jobin-Gilroy was asked if she was interested in the trial after being hospitalized for a month due to lupus nephritis.

Jobin-Gilroy reported she felt some dizziness after her therapies in this trail (Like White, Jobin-Gilroy does not know whether she received belimumab or the placebo.) After the trial, Jobin-Gilroy said she is still doing well. “Now I can walk and feel like I have a lot more energy. I can do my daily routine easier now,” she said.

Limits to Keep in Mind

It’s important to keep in mind that all studies and drugs have limits. Belimumab was effective for some patients, a significant portion of patients don’t receive any benefit. While 43% of participants taking belimumab did improve based on the study’s benchmarks, this is only 11% more patients than those who received the placebo.

Like earlier clinical trials of belimumab, not many Black patients were enrolled in the new trial, with 31 Black patients in the belimumab group and 32 Black patients in the placebo group. Black people are three times more likely to die from lupus complications than white people with lupus. Black people enrolled in this trial experienced a lower response to belimumab compared to patients overall. Earlier clinical trials had a similar result.

Like other biologic medications, belimumab is expensive. In 2012, it was estimated to cost patients $35,000 a year (pre-insurance or patient support) at either $443 or $1,477 per vial. The cost has likely increased since then. According to GoodRx, a drug discount finder, one carton of four 200/mg belimumab autoinjectors costs about $3,750.

GlaxoSmithKline, the manufacturer of the drug, sponsored the latest clinical trial to expand belimumab’s FDA approval to cover lupus nephritis. Furie and others associated with this trial disclosed financial connections with the company, which you can see here. The results of the two-year randomized study were published in The New England Journal of Medicine on Sept. 17.

What’s Next for Patients

From here, Furie and his team are hopeful belimumab will be FDA-approved to treat lupus nephritis. If it is approved by the FDA, it would be the first drug to treat the common lupus complication. In addition to its 2011 FDA approval, belimumab was also approved in 2019 for use in children with lupus.

Despite the progress of his belimumab clinical trial for lupus nephritis and other treatment developments in the works, Furie believes even more research is needed to continue helping patients and improving health outcomes.

“Our job is not over with those drugs and I’m not even sure our job is over with belimumab,” Furie said. “But it’s a step in the right direction.”