Lilly and Incyte Announce Additional Phase IIb Baricitinib Data, Including MRI Results, in Patients with Rheumatoid Arthritis
Positive results of the placebo-controlled 12-week portion of the study were presented at the European League Against Rheumatism's (EULAR) Annual
Response at 24 weeks |
2 mg (n=52) |
4 mg |
8 mg |
ACR20 |
63 |
78 |
73 |
ACR50 |
20 |
48 |
55 |
ACR70 |
10 |
28 |
24 |
"These data are important because collectively they show patients experienced improvement with baricitinib as early as week two that was sustained through week 24," said
Also Presented: MRI Findings
The study also included a large sub-study of 154 patients using Magnetic Resonance Imaging to examine the effect of different doses of baricitinib on joint changes in a subgroup of patients with erosive RA and inadequate response to treatment with methotrexate. There was statistically significant improvement in both the Total Inflammation Score and the Total Joint Damage Score for both 4 mg and 8 mg baricitinib doses compared with placebo at 12 weeks. The effects persisted through 24 weeks.
"This sub-study illustrates not only the efficacy of oral baricitinib in suppressing joint damage in RA, but also the power of MRI to demonstrate therapeutic effects in RA on synovitis, osteitis, bone erosion and even articular cartilage loss far more quickly (within only 12 weeks) and with far fewer patients than would be needed with conventional radiography," said
"We believe the janus kinase inhibitors are an innovative class of molecules which we hope have the potential to improve outcomes for patients with diseases such as rheumatoid arthritis. We are very encouraged about the results for baricitinib, which represent the first 24-week clinical data for a selective JAK1 and JAK2 inhibitor in RA," said Eiry Roberts, M.D., vice president of autoimmune product development at Lilly. "Based on the benefit/risk data from the Phase II program for baricitinib, we recently moved ahead with Phase III clinical trials in RA."
Safety Results
In the 12-week portion of the study, the most common treatment-emergent adverse event (TEAE) class was infections, with a similar rate observed among patients in the placebo group (12 percent) and patients receiving baricitinib (14 percent).
Over 24 weeks in the combined 2 mg, 4 mg and 8 mg groups, the rate of TEAEs was 64 percent (36 percent mild, 23 percent moderate, 5 percent severe) and the rate of serious adverse events was 5 percent.
There were no opportunistic infections and no deaths reported through week 24. Dose-dependent changes in laboratory tests (hemoglobin, lymphocyte and neutrophil count, low-density lipoprotein and high-density lipoprotein) were observed, with greater changes being observed in the 8 mg baricitinib group than in the 2 mg and 4 mg groups.
Trial Design and Status
This Phase IIb randomized double-blind, placebo-controlled, dose-ranging study, known as
In the initial 12-week treatment duration, patients received one of four doses of baricitinib or placebo. In the 12- to 24-week portion of the study, patients initially randomized to placebo or the 1 mg baricitinib dose were re-randomized to receive either 4 mg once daily or 2 mg twice daily for an additional 12 weeks; patients initially randomized to the 2 mg, 4 mg and 8 mg doses continued therapy with those doses. Patients are continuing to participate in the open-label long-term extension phase of the trial.
About JAK Inhibition
There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. These enzymes are critical components of signaling mechanisms used by a number of cytokines and growth factors, including those that are elevated in RA patients. Cytokines such as interleukin-6, -12 and -23 and both type 1 and type 2 interferons signal through the JAK/
About Baricitinib
Baricitinib is an orally administered selective JAK1 and JAK2 inhibitor that spares JAK3. Baricitinib is advancing into Phase III development as a potential treatment for rheumatoid arthritis and it is in Phase II development as a potential treatment for psoriasis and diabetic nephropathy.
Four Phase III RA studies are planned, which will investigate the safety and efficacy of baricitinib 2 mg and 4 mg once daily in patients with active RA who are methotrexate-naive, biologic-naive or biologic-experienced. Patients completing any of the four studies will be eligible for enrollment in a fifth study, a long-term extension.
In
About Rheumatoid Arthritis
Rheumatoid arthritis is characterized by abnormal immune mechanisms that lead to joint inflammation and swelling with progressive destruction of joints. In addition to affecting the joints, RA also can affect connective tissue in the skin and organs of the body.[2]
Current treatment of RA includes the use of non-steroidal anti-inflammatory drugs, oral disease-modifying antirheumatic drugs such as methotrexate, and injectable biological response modifiers that target tumor necrosis factor, a pro-inflammatory cytokine implicated in the pathogenesis of RA.
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Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in
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This press release contains certain forward-looking statements about baricitinib as a potential treatment for patients with rheumatoid arthritis and reflects Lilly and
P-LLY
[1] Edward Keystone, "Safety and Efficacy of LY3009104 (JAK1/JAK2 inhibitor) in RA Patients with Inadequate Response to MTX" (presented at the Annual
[2]
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