AbbVie's Rinvoq Succeeds Against The Odds In Phase II Lupus Trial

Despite a troubled history of JAK inhibitors in lupus trials, AbbVie’s Rinvoq has hit the mark in a mid-stage study of the condition, shifting focus to a pivotal program that could expand the blockbuster drug’s reach.

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Rinvoq Is Now Progressing To A Phase III Lupus Program

 

Key Takeaways:

• More than half of patients treated with Rinvoq saw a minimum four-point reduction in their disease score.

• Rinvoq will now move into the Phase III SELECT-SLE program for lupus.

• Rival Bristol Myers Squibb’s TYK2 inhibitor Sotyktu is slightly ahead in the race to market.

AbbVie Inc.’s JAK inhibitor Rinvoq has hit the bullseye in a Phase II systemic lupus erythematosus (SLE) trial, sparking hopes for a pivotal program in the works, even though a Rinvoq combination with the firm’s selective BTK inhibitor candidate, elsubrutinib, disappointed

Rinvoq (upadacitinib) is currently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ankylosing spondylitis, axial spondyloarthritis and ulcerative colitis and earlier this month won a label expansion to Crohn’s disease. Full-year 2022 revenues of the product rocketed by 52.8% to $2.52bn. (Also see "Rinvoq Approved For Crohn’s Disease In Pivotal Year For AbbVie’s Immunology Business" - Scrip, 19 May, 2023.)

The Phase II SLEek trial randomized 341 SLE patients undergoing standard therapy to either once-daily high dose Rinvoq plus elsubrutinib, low dose Rinvoq plus elsubrutinib, Rinvoq plus placebo, elsubrutinib plus placebo or two placebo pills. During a previous interim analysis, AbbVie discontinued the low-dose Rinvoq plus elsubrutinib arm and the elsubrutinib plus placebo arm due to a lack of efficacy.

Now, topline data have revealed that more patients receiving single-agent Rinvoq or high-dose Rinvoq plus elsubrutinib met the trial’s dual primary endpoint at 48 weeks when compared with placebo. This endpoint comprised a minimum four-point reduction in the Systemic Lupus Erythematosus Disease Activity Index 2000 score and a maximum steroid dose of 10mg prednisone or equivalent once a day.

In the single-agent arm, 54.8% of patients achieved the primary endpoint versus 37.3% of those on placebo (p=0.028). While high-dose Rinvoq plus elsubrutinib missed significance with 48.5% of patients meeting the primary endpoint (p=0.081), the outcome was unsurprising seeing as at the time of the interim analysis, AbbVie had announced it did not plan to advance the combination as elsubrutinib did not contribute efficacy.

The firm instead touted plans to progress Rinvoq into the Phase III SELECT-SLE program, which comprises three studies and will investigate the drug versus placebo in 1,000 people with moderately to severely active lupus, according to ClinicalTrials.gov. While the trial has not yet started recruiting, it will measure the percentage of participants achieving a British Isles Lupus Assessment Group Based Combined Lupus Assessment (BICLA) response at 52 weeks as a primary endpoint.

Rinvoq’s largest indication is axial spondyloarthritis, a form of arthritis that affects around 3.2 million people in the US, but a label expansion to SLE could open up a market of 1.5 million more patients in the region. SLE is a complex autoimmune disorder characterized by fatigue, joint pain and impaired function among other symptoms and there is no cure for it.

Standard of care only addresses symptoms with little effect on disease progression. For example, over-the-counter NSAIDs, such as ibuprofen and naproxen, and corticosteroids are used to alleviate pain and swelling. Given the resultant high unmet need, there has been a surge of innovation in the lupus space in recent years.

In 2021, AstraZeneca PLC’s type I interferon inhibitor Saphnelo (anifrolumab) became the first new drug to be approved for SLE for more than a decade. The same year, Otsuka Holdings Co., Ltd./Aurinia Pharmaceuticals Inc.’ calcineurin inhibitor Lupkynis (voclosporin) became the first oral treatment approved for lupus nephritis. (Also see "AstraZeneca To Challenge GSK After Clinching Lupus Drug Approval" - Scrip, 3 Aug, 2021.)

However, attempts to break into the lupus market through JAK inhibition have largely failed to date, making Rinvoq’s smooth ride thus far particularly impressive. Last year, rival Eli Lilly and Company turned its back on pursuing an SLE label expansion for its oral JAK inhibitor Olumiant (baricitinib) after the drug failed to replicate primary endpoint success in the second of a pair of Phase III trials. (Also see "Lilly Says Safety Not A Factor In Dropping Lupus Development With Olumiant" - Scrip, 28 Jan, 2022.)

In 2019, Gilead Sciences, Inc. and Galapagos NV's JAK Inhibitor Jyseleca (filgotinib) missed the primary endpoint in a mid-stage lupus trial. Despite these headwinds, there are five other JAK inhibitors in active clinical development for the treatment of SLE, according to the Citeline database Pharmaprojects.

Notable contenders include Bristol Myers Squibb Company’s TYK2 inhibitor Sotyktu (deucravacitinib), which is in Phase III development for the condition, and Pfizer Inc./Roivant Sciences Ltd.’ first-in-class dual TYK2/JAK1 inhibitor, which is slightly behind at Phase II. (Also see "Bristol Confident To Move Deucravacitinib Into Phase III Lupus Trial" - Scrip, 1 Jun, 2022.)