Upadacitinib headed to Phase 3 testing in SLE

Treatment with upadacitinib in Phase 2 trial yielded significant positive results

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Treatment with upadacitinib led to a significant reduction in disease activity for people with moderate-to-severe systemic lupus erythematosus (SLE) in a Phase 2 clinical trial, according to top-line results announced by its developer, AbbVie.

Based on these positive results, AbbVie now is planning to advance upadacitinib to Phase 3 clinical testing — a larger trial designed to comprehensively assess the therapy’s effectiveness and identify rare safety issues.

“Systemic lupus erythematosus is a very unpredictable life-long condition and the way it affects a patient can change over time. Therefore, there is a critical need for additional treatment options,” Roopal Thakkar, MD, said in a press release. Thakkar is senior vice president of development and regulatory affairs and chief medical officer at AbbVie.

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“We look forward to further evaluation of the potential benefits that upadacitinib could bring to patients,” Thakkar said.

Upadacitinib works by blocking the activity of Janus kinases (JAKs), which are proteins that help to coordinate molecular signaling processes inside immune cells. By blocking JAKs, the therapy may help to reduce immune cell activity, thus decreasing the inflammation that drives autoimmune diseases like lupus.

Upadacitinib is currently approved in the U.S. to treat certain forms of arthritis, inflammatory bowel disease, and dermatitis (eczema). AbbVie markets the therapy for these indications under the brand name Rinvoq.

The company conducted a Phase 2 clinical trial (NCT03978520) to explore the safety and efficacy of upadacitinib in SLE. The study also evaluated the effectiveness of elsubrutinib, an experimental therapy that works by blocking another immune cell signaling protein called Bruton’s tyrosine kinase (BTK). AbbVie is developing a combination of upadacitinib and elsubrutinib under the name ABBV-599.

The study enrolled 341 adults with lupus, who were assigned randomly to one of five groups. Two groups received different doses of upadacitinib in combination with elsubrutinib. Another two groups received either upadacitinib or elsubrutinib along with a placebo version of the other medicine. The fifth group received only placebo.

Study’s main goal

The study’s main goal was to assess the number of patients who met the SLE Responder Index-4 (SRI-4) criteria with a daily steroid dose equivalent to 10 mg prednisone or lower after 24 weeks (about six months). SRI-4 is a composite measure of disease severity that basically means patients have improved in some measures of disease activity, without worsening in others.

The study reached its goal, with higher response rates being observed in the upadacitinib 30 mg group, according to AbbVie. The company did not provide specifics on efficacy results, noting that full results will be presented at future medical conferences.

Safety data from the Phase 2 trial were generally consistent with the known safety profile of upadacitinib. The safety profile of the combination of upadacitinib and elsubrutinib was generally similar to that of upadacitinib alone. Among other safety data, upadacitinib is known to increase the risk of infections.

Its label for other approved indications includes a boxed warning stating the medication increases the risk of serious bacterial, viral, fungal, and opportunistic infections leading to hospitalization or death.