New Drug Approved for Lupus

By Jill Tyrer

People living with systemic lupus erythematosus (SLE) have a new drug option. The U.S. Food and Drug Administration approved anifrolumab (Saphnelo) in early August — the first new drug approved for SLE in 10 years.

“I think this drug approval for lupus represents an important milestone,” says Mary K. Crow, MD, Benjamin M. Rosen Chair in Immunology and Inflammation Research and co-director of the Mary Kirkland Center for Lupus Research at Hospital for Special Surgery (HSS).

There is no cure for SLE, a complex autoimmune disease that can affect joints, skin and organs. The last new drug approved for the disease was belimumab (Benlysta) in 2011 — and that was the first new drug approved for SLE in decades, Dr. Crow says.

Anifrolumab is approved for people with moderate-to-severe SLE who are using other medications for lupus, like corticosteroids (commonly called “steroids”). It is delivered by infusion, and trials for injectable forms that can be administered by the patient are underway. Drugmaker AstraZeneca didn’t respond to questions about when it will become available.

“The investigators who participated in the trials were impressed by the improvement in skin disease seen in some patients, and that bore out in the data that came out of the trials. So lupus patients with significant skin involvement might be particularly appropriate candidates for trying anifrolumab,” Dr. Crow says.

Another benefit: It may help reduce the use of more toxic drugs, like corticosteroids, cyclophosphamide (Cytoxan) or azathioprine. “The treatments [for lupus] are not ideal. Particularly the use of steroids over long periods of time can cause damage. And some of the drugs, like azathioprine and cyclophosphamide, do have significant toxicity,” Dr. Crow says. The trials showed that patients using anifrolumab were able to reduce their use of steroids, which are effective in controlling disease, “but patients hate them because they have so many long-term side effects that can be very damaging,” she adds.

Still, Dr. Crow says, “I don’t think [anifrolumab] would be the first drug you would try. Most lupus patients are treated with hydroxychloroquine [Plaquenil], which is a fairly benign drug. It’s not a super potent drug but it does a pretty good job of controlling disease activity in many patients,” she says. “I think many lupus patients could be considered for anifrolumab if they’re not responding to other medications.”

Once the drug becomes available, it will take some time to learn where it fits in the lupus treatment toolbox. Just as when belimumab was introduced, “it took a few years to really understand how to use the drug: At what point in the course of disease, what kind of disease activity responded best? I think the same is going to be true here,” Dr. Crow says.

The most significant potential side effect is an increase in the risk of developing herpes zoster (shingles), so anyone starting it would need to be vaccinated for shingles first, Dr. Crow says. Some people in the trials also developed upper respiratory infections. 

“A Good Year for Lupus”

This is the latest of several treatments approved for lupus patients recently, following two drugs — voclosporin (Lupkynis) and belimumab — approved earlier this year to treat lupus nephritis, which is kidney disease caused by SLE.

“This is actually a pretty good year for lupus patients,” Dr. Crow says.

The approval of anifrolumab has been much anticipated since the results of the phase 2 trial came out, but it wasn’t all smooth sailing.

“The phase 2 study was fantastic. It really had outstanding results across skin and joints and overall disease activity,” Dr. Crow says. However, the first phase 3 trial didn’t meet its endpoint, meaning the results were not as expected. Yet the drug did meet its endpoint in the second phase 3 trial, showing that it did have efficacy.

Typically, the FDA wants two successful phase 3 trials, but in an unusual move, it considered all the results together, “and the clear message was that the drug had efficacy as well as safety, so they approved it.”

Anifrolumab is a monoclonal antibody that works by blocking the interferon 1 receptor. Interferons are members of an “immune system family of cytokines that rally the immune system to fight virus infections,” Dr. Crow explains. In lupus, however, the cells keep making type 1 interferon without shutting it off, “so all of that immune activation persists over months and years.”

As a result, anifrolumab should be effective for lupus patients with “high activation of the interferon pathway.” Not all patients fit that profile, but most do — about 80% of those in the HSS studies, Dr. Crow says.

Future of Lupus

“Lupus is such a complicated disease. It's been so hard to design informative clinical trials, so there have been many — I don’t know if I should call them failures — but that didn’t meet their endpoints, even though the mechanisms of the drugs seemed reasonable,” Dr. Crow says.

However, those many “failures” have added to the body of knowledge and understanding of lupus and how the disease works. As a result, a remarkable number of drugs targeting many different pathways and disease activities are currently being investigated.

Dr. Crow found nearly 700 clinical trials for lupus underway in clinicaltrials.gov. “They’re not all drug studies, but most of them are, and there are so many different drugs and mechanisms being tested for lupus,” she says. “Ten or 15 years ago, there were not many drugs being tested, and most trials were not successful. There’s been a lot of experience gained related to clinical trial design and most significantly, new understanding of the mechanisms of disease through research studies, so new ideas about how to target the disease therapeutically have been developed.”

While other drug options may become available in the next few years, anifrolumab may provide relief for some patients who haven’t yet found the right treatment for their lupus.

“I think patients should be very pleased that there’s a new drug approved for lupus that might improve their care,” Dr. Crow says. “It’s not going to be used in everyone, but I feel confident that there will be lupus patients who benefit from it.”