Anifrolumab Shows Promise for Lupus

December 17, 2015
Stephanie Pappas

A Phase II trial of a new monoclonal antibody drug shows promise for a potential new treatment for lupus.

A Phase II trial of a new monoclonal antibody drug shows promise for a potential new treatment for systemic lupus erythematosus. If the results hold, anifrolumab could become only the second new drug approved to treat the disease in more than 50 years.

In a randomized, double-blind study, anifrolumab outperformed a placebo in improving the symptoms of moderate to severe systemic lupus erythematosus, researchers reported November 10 at the annual meeting of the American College of Rheumatology in San Francisco.[[{"type":"media","view_mode":"media_crop","fid":"44367","attributes":{"alt":"©Artemida-psy/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_8548901060130","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4951","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©Artemida-psy/Shutterstock.com","typeof":"foaf:Image"}}]]

Anifrolumab is a type I interferon receptor antagonist. It's been granted fast-track status by the Food and Drug Administration, a designation reserved for drugs that aim to fill a serious and unmet need. Anifrolumab's maker, MedImmune, is the biologics development subsidiary of AsteraZeneca.

In an interview with Rheumatology Network, Jorn Drappa, the vice president of clinical biologics and respiratory, inflammation and autoimminity at MedImmune, said the group is simultaneously testing another drug, sifalimumab, which targets the interferon alpha protein itself. Phase II trials in both drugs have returned positive results.

The joint results "very clearly validated the interferon hypothesis," Drappa said.

Both drugs come at the pathway from different directions, with anifrolumab targeting the receptor and sifalimumab targeting the protein. So far, anifrolumab's Phase II results outpace sifalimumab's, which had smaller effect sizes than hoped, Drappa said.

The researchers randomized 305 adults with moderate to severe systemic lupus erythematosus to receive either intravenous anifrolumab in 300 mg or 1,000 mg doses or a placebo every four weeks for 48 weeks. The primary endpoint was scores on the Systemic Lupus Erythematosus Responder Index (SLR-4), combined with a measure of steroid sparing.

At day 169 of the trial, the primary endpoint had been met by 34.3 percent of patients receiving the 300 mg dose of anifrolumab compared with 17.6 percent of those receiving a placebo (p=0.014). 28.8 percent of those receiving the 1000 mg dose of the drug met the primary endpoint as well (p=0.063). At day 365, the secondary SRI end point was met by 56.4 percent of the patients taking a 300 mg dose of anifrolumab, 31.7 percent of those taking a 1000 mg dose (p=0.595) and 26.6 percent of those taking a placebo (p=0.001 for the 300 mg dose and p=0.595 for the 1000 mg dose).

The lack of dose-response was likely due to the fact that even the lower dose suppressed around 90 percent of activity in 21 interferon-regulated genes, the researchers reported.

The trial also demonstrated that patients with a high interferon gene signature  responded better to anifrolumab than those with a low interferon gene signature.

"It's particularly exciting because we may be able to provide clinicians with an understanding of which of their patients might be able to respond to those therapies by looking at the interferon signature test," Drappa said.

Patients taking anifrolumab did report a higher frequency of influenza, with 7.5 percent on the 1000 mg dose and 6.1 percent on the 300 mg dose reporting the flu compared with 1 percent of the placebo group. Most cases were unconfirmed, however. There was a dosage-dependent increase in Herpes zoster cases, with 9.5 percent of the 1000 mg dose group reporting cases compared with 5.1 percent of the 300 mg group and 2 percent of the placebo group.

"With any drug that targets the immune system, there is always the concern of infection, so that is something we're looking at very carefully," Drappa said.

The ACR abstract presenting the trial data was highlighted for a discussion by the Rheumatology Journal Club on Dec. 10 by a group of rheumatologists polled on Twitter.  Led by Christopher E. Collins, MD, an associate professor of medicine at Georgetown University Medical Center and a member of the Rheumatology Network Editorial Board, the group noted the rapid skin response seen in the Phase II data - a finding that makes sense, Collins wrote on Twitter, given the high interferon signature in the skin in systemic lupus erythematosus.

The discussion also focused on the use of steroid sparing as an outcome measure.

"We need more real life data with these drugs to see how we are able to manage steroids in these patients," Collins wrote.

The interest in the abstract spotlights the high hopes for anifrolumab. The last drug approved for the treatment of lupus was Benlysta (belimumab) in 2011, the first drug approval for lupus since 1955. Benlysta targets abnormal B cells by inhibiting  B-lymphocyte stimulator (BLyS) protein.

Phase III trials of anifrolumab have begun, Drappa said, and a Phase II trial for the use of anifrolumab in lupus nephritis is also ongoing.

"This is by far the most clear-cut result of any drug that has ever been tested in Phase II" for systemic lupus erythematosus, Drappa said. "I think clinicians will be glad to know there is certainly another option for a target biologic therapy for lupus patients on the horizon."

 

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