Phase 2 Study of Upadacitinib (RINVOQ) Alone or as a Combination Therapy Meets Primary and Key Secondary Endpoints in Patients with Systemic Lupus Erythematosus
May 31, 2023 – Clinical Trials –
North Chicago, Illinois, US – 31 May 2023 – PRNewswire – AbbVie (NYSE: ABBV) today announced the results of the Phase 2 SLEek study evaluating upadacitinib (RINVOQ 30 mg) alone and in combination [ABBV-599 high dose (elsubrutinib 60 mg and upadacitinib 30 mg)] in adults with moderately to severely active systemic lupus erythematosus (SLE) who continued to receive standard lupus therapies. The study results are being presented as an oral presentation during the European Congress of Rheumatology, EULAR 2023.
In the phase 2 SLEek study, a greater proportion of patients receiving upadacitinib 30 mg or ABBV-599 high dose achieved the primary endpoint, SLE Responder Index (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%; p=0.028 and 48.5%; p=0.081* versus 37.3%, 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.
‘There are limited treatment options for people living with SLE, leaving physicians challenged on how to effectively slow disease progression and limit potential organ damage in their patients,’ said Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer, AbbVie. ‘As a leader in immunology, AbbVie is committed to advancing care in areas of unmet need, such as SLE. We are encouraged by these positive phase 2 data and look forward to continuing to study upadacitinib for systemic lupus erythematosus in two phase 3 trials as part of our ongoing clinical program.’
Key secondary endpoints were also achieved at week 48 in both active treatment groups, including lupus flares measured by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) and time to first flare, which showed greater treatment effect in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo. Other measures of disease activity and treatment response were also met, including achievement of BICLA response, SRI-4, and Lupus Low Disease Activity State (LLDAS) in the upadacitinib 30 mg and ABBV-599 high dose groups compared to placebo.
SLE – the most common type of lupus – is an autoimmune disease where the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can impact the joints, skin, brain, lungs, kidneys and blood vessels, causing a variety of symptoms, including fatigue, skin rashes, fevers, and pain and swelling in the joints. Disease activity in lupus – often called flares – is unpredictable. Flares can appear without warning, come and go and vary in severityóserious flares can cause organ damage and require medical attention.
‘Lupus is an imbalance in the immune system caused by a diverse set of inherited and environmental factors. It impacts over three million people around the world and causes an overlapping spectrum of symptoms,’ said Joan Merrill, M.D., Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program. ‘To achieve sustainable progress with SLE, we need more treatment options for patients with this disease.’
No new safety signals were observed beyond the known safety profile for upadacitinib. Types of adverse events reported with ABBV-599 high dose were similar to those reported for patients treated with upadacitinib alone. The rate of treatment emergent adverse events (TEAEs) in this study were similar across groups (ABBV-599 at 86.8%, upadacitinib at 82.3% and placebo at 78.7% ). Serious AEs were reported in 10.3% of patients in the ABBV-599 high dose, 21.0% in upadacitinib 30 mg, and 17.3% in placebo groups. Adjudicated cardiovascular events were reported in one patient in each of the three treatment groups. There were no reports of malignancies or venous thromboembolic events. The use of upadacitinib and elsubrutinib in SLE are not approved and their safety and efficacy have not been evaluated by regulatory authorities.
