Phase 2 SLEek Clinical Trials Showed Promising Results for Patients With Systemic Lupus Erythematosus

The ABBV-599 Phase 2 SLEek studyclinical trial met the endpoint goals for efficacy and safety in the treatment of systemic lupus erythematosus (SLE). ABBV-599 is a combination of elsubrutinib (ELS), which is a selective BTK inhibitor, and upadacitinib (UPA), which is a JAK inhibitor. The treatment targets non-overlapping signaling pathways associated with SLE. Joan Merrill, MD, and investigator at the Oklahoma Medical Research Foundation, has been involved in lupus clinical trials for more than 30 years. She presented the trial results at the 2023 European Congress of Rheumatology in Milan, Italy held May 31-June 3, 2023.¹

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“I was involved in the study, from the beginning, giving advice and working on the team that designed the trial,” she explained. “A new thing we're doing in lupus trials is taking seasoned lupus investigators, and actually monitoring the data for quality to make sure that when the patients enter the trial, they have enough disease activity that's due to lupus and not some other condition, and that the patient's stable enough to participate in a trial without a great risk.”

Merrill’s passion for lupus investigation stems from seeing the painful rashes, lesions, ulcerations, and alopecia patients experience and wanting to help improve their quality of life. “As an older woman, I feel for anybody who has to deal with that [alopecia] because it's not fun. It can be quite relentless.”

Participants (n=341) in the Phase 2 SLEek study were chosen at random to receive either ELS 60 mg and UPA 15 mg, ELS 60 mg, UPA 30 mg, or a placebo. More than half of patients reached week 24 or withdrew from the study. In a press release, AbbVie disclosed that the “ABBV-599 low dose and ELS 60 mg arms were discontinued for lack of efficacy.” Nearly 200 patients continued to week 48 with ABBV-599 high dose (n=68), UPA 30 mg (n=62), and placebo (n=65).

Study investigators measured the primary endpoint based on the SLE Responder Index (SRI-4). In their published study results, they said, “A greater proportion of patients receiving UPA30 mg or ABBV-599 high dose achieved the primary endpoint, SRI-4 and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24, compared to placebo (54.8 percent; p=0.028 and 48.5 percent; p=0.081* versus 37.3 percent, respectively). SRI-4 and steroid dose less than or equal to 10 mg prednisone equivalent per day assess reductions in disease activity and glucocorticoid use, respectively.”

The clinical trial also achieved secondary endpoints at week 48 in both active treatment groups.

Secondary endpoints were also achieved at week 48 in both active treatment groups compared to the placebo.Lupus flares measured lower, according to measurement of the Safety of Estrogens in Lupus Erythematosus National Assessment, Systemic Lupus Erythematosus Disease Activity Index, and Lupus Low Disease Activity State.

Merrill explained that both formulations left investigators optimistic.

“Either way...both of those formulations were successful at meeting the primary endpoint, which was a composite endpoint where you had to get better by one disease activity score, and you couldn't get worse by any of the others,” Merrill said. “It was added to the fact that you had to get your steroids down really low...Both of those met the primary endpoint, and both met many or most of the secondary endpoints.”

Merrill shared with Dermatology Times® that she is excited and hopeful as AbbVie advances to Phase 3 clinical trials for upadacitinib in SLE. ABBV-599 will not move forward since there was no proof of efficacy by elsubrutinibrelative to upadacitinib alone.

Reference

1. Phase 2 study of Upadacitinib (RINVOQ®) alone or as a combination therapy meets primary and key secondary endpoints in patients with systemic lupus erythematosus. News Center. May 31, 2023. Accessed June 2, 2023. https://news.abbvie.com/news/press-releases/phase-2-study-upadacitinib-rinvoq-alone-or-as-combination-therapy-meets-primary-and-key-secondary-endpoints-in-patients-with-systemic-lupus-erythematosus.htm.