Benzinga | Oct 7, 2021 08:17AM EDT

AbbVie Reports Upadacitinib Met Primary, Most Secondary Endpoints In Phase 3 Study For Non-Radiographic Axial Spondyloarthritis

- In Study 2 of the Phase 3 SELECT-AXIS 2 clinical trial, upadacitinib (RINVOQ(r)) met the primary endpoint of ASAS40 at week 14 versus placebo (45 percent compared to 23 percent)[1]

- The first 12 of 14 ranked secondary endpoints were met[1]

- Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications and the known safety profile of upadacitinib, with no new risks identified[1-6]

- Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy in several immune-mediated diseases[1,6-14]

NORTH CHICAGO, Ill., Oct. 7, 2021 /PRNewswire/ -- AbbVie (NYSE:ABBV) today announced positive top-line results from Study 2 of the Phase 3 SELECT-AXIS 2 clinical trial in adults with active non-radiographic axial spondyloarthritis (nr-axSpA), showing upadacitinib (RINVOQ(r); 15 mg, once daily) met the primary endpoint of Assessment in SpondyloArthritis International Society (ASAS) 40 response and the majority of ranked secondary endpoints at week 14.1 Significantly more upadacitinib-treated patients achieved ASAS40 response at week 14 compared to placebo (45 percent versus 23 percent; p<0.0001).1

SELECT-AXIS 2 is the first trial to evaluate the efficacy and safety of upadacitinib in adult patients with non-radiographic axial spondyloarthritis.1 Earlier today, AbbVie announced positive results from Study 1 of SELECT-AXIS 2 in adults with active ankylosing spondylitis (AS) and inadequate response to biologic disease-modifying antirheumatic drugs (bDMARDs).1

"People living with active non-radiographic axial spondyloarthritis suffer from chronic inflammatory back pain and limited physical function that can be very debilitating," said Michael Severino, M.D., vice chairman and president, AbbVie. "These patients need treatments that help them improve their physical function and quality of life. We are encouraged by the potential of upadacitinib in helping to provide relief of these signs and symptoms through meaningful disease control."

Treatment with upadacitinib resulted in reductions in signs and symptoms of non-radiographic axial spondyloarthritis, including back pain and inflammation, as well as improvements in physical function and disease activity at week 14.1 Significantly more patients treated with upadacitinib achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) Low Disease Activity compared to those treated with placebo (42 percent versus 18 percent; p<0.0001).1 A statistically significantly improvement in Magnetic Resonance Imaging (MRI) Spondyloarthritis Research Consortium of Canada (SPARCC) Score (SI Joints) as measured by mean change from baseline was reported in the upadacitinib group versus the placebo group (-2.49 versus 0.57; p<0.0001).1 Patients on upadacitinib experienced significantly greater decrease from baseline in Patient's Assessment of Total Back Pain at week 14 than those on placebo (-2.91 versus -2.00; p=0.0004).1 Additionally, patients treated with upadacitinib experienced significantly greater improvement in physical function as assessed by mean change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) compared to patients on placebo (-2.61 versus -1.47; p<0.0001).1

SELECT-AXIS 2 (Study 2) Efficacy Results at Week 14&#x2A;,1

Upadacitinib 15 mg,Placebo once daily (n=157) (n=156)

Percent of Patients achieving ASAS40a 45% 23%

Percent of Patients achieving ASDAS Low Disease42% 18% Activityb

Mean Change from Baseline in Magnetic Resonance-2.49 0.57 Imaging (MRI) SPARCC Score (SI Joints)c

Mean Change from Baseline in Patient's -2.91 -2.00 Assessment of Total Back Paind

Mean Change from Baseline in BASFIe -2.61 -1.47

&#x2A;Primary and ranked secondary endpoints at week 14. Not all ranked secondary endpoints are shown. All endpoints shown with the exception of total back pain (p=0.0004) achieved p-values of <0.0001 versus placebo.

a ASAS 40 is defined as a ?40 percent improvement and an absolute improvement of ?2 units (on a scale of 0 to 10) from Baseline in at least 3 of the 4 domains (patient's global assessment, back pain, function and inflammation) with no worsening at all in the remaining domain.

b ASDAS Low Disease Activity is defined as ASDAS score <2.1.

c SPARCC scores for SI-Joints are calculated by adding up the dichotomous outcomes from evaluations of the presence, depth, and intensity of bone marrow edema lesions of the SI-joints.

d Back Pain is measured using 0 - 10 numerical rating scale (NRS) for Total Back Pain (0 = no pain and 10 = severe pain).

e BASFI is a validated patient-reported outcome (PRO) instrument for use in the axial SpA patient population. It consists of 10 items measured on a 0 to 10 NRS, which assesses the ability to perform activities known to be problematic to axial SpA patients such as dressing, bending, reaching, turning, and climbing steps. The total scores range from 0 to 10.

"Non-radiographic axial spondyloarthritis affects a younger adult patient population which can have a significant impact during prime years of those dealing with the disease," said Atul Deodhar, M.D., professor of medicine and medical director of the Rheumatology Clinics for the Division of Arthritis and Rheumatic Diseases at Oregon Health & Science University. "These data show that upadacitinib has the potential to improve non-radiographic axial spondyloarthritis symptoms and help patients take control of their disease."

Safety data were consistent with SELECT-AXIS 1, previous Phase 3 studies in other indications, and the known safety profile of upadacitinib, with no new risks identified.1-6 Through week 14, the most common adverse events (? 3 percent of patients) with upadacitinib were headache, COVID-19, nasopharyngitis and nausea.1 The proportion of patients with adverse events leading to discontinuation, serious adverse events and serious infections were 2.6 percent/2.6 percent/1.3 percent for upadacitinib and 1.3 percent/1.3 percent/0.6 percent for placebo, respectively.1 Serious infections included COVID-19 induced pneumonia and pyelonephritis in two patients on upadacitinib and hemorrhagic fever with renal syndrome in one patient on placebo.1 Two patients treated with upadacitinib and one treated with placebo developed non-serious, mild or moderate herpes zoster limited to one dermatome.1 One patient treated with placebo developed a malignancy (basal cell carcinoma).1 No adjudicated major adverse cardiovascular events, venous thromboembolic events or deaths were reported in either group through week 14.1

Full results from the SELECT-AXIS 2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Use of upadacitinib in non-radiographic axial spondyloarthritis is not approved, and its safety and efficacy have not been evaluated by regulatory authorities.