Lilly and Incyte Announce Additional Phase IIb Baricitinib Data,
Including MRI Results, in Patients with Rheumatoid Arthritis
WASHINGTON, Nov. 13, 2012 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte Corporation (Nasdaq: INCY) today
announced 24-week results from the continuation of an ongoing Phase
IIb study of baricitinib, an orally available janus kinase (JAK)
inhibitor, in patients with moderate-to-severe rheumatoid arthritis
(RA) who had an inadequate response to treatment with methotrexate.
Additionally, Magnetic Resonance Imaging (MRI) technology was used
in a sub-study to examine the effect of baricitinib on joint
erosion and other markers of structural changes in and around the
joint. The findings were presented at the annual meeting of the
American College of Rheumatology (ACR) in Washington, D.C.
Positive results of the placebo-controlled 12-week portion of
the study were presented at the European League Against
Rheumatism's (EULAR) Annual European Congress of Rheumatology in
June 2012.[1] Patients taking baricitinib 4 mg or 8 mg once daily
reported significant differences in ACR20, ACR50 and ACR70
responses compared with patients taking placebo. Data from the 12-
to 24-week portion of the study, which did not include a placebo
control, showed that patients who continued to receive 2 mg, 4 mg
or 8 mg baricitinib once daily doses maintained or improved ACR20,
ACR50 and ACR70 responses. The following chart defines the
percentage of patients that achieved ACR20, ACR50 and ACR70 at 24
weeks of treatment with baricitinib.
Response at 24 weeks
|
2
mg
(n=52)
|
4
mg
(n=52)
|
8
mg
(n=50)
|
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 Mark Genovese, M.D., the James Raitt professor of medicine and co-chief,
division of immunology and rheumatology at Stanford University School of Medicine in
Palo Alto, Calif., and steering
committee member for the study. "Also of note is that the
percentage of patients achieving ACR50 and ACR70 increased over
time and no unexpected safety findings emerged with continued
dosing."
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 Charles Peterfy, M.D., Ph.D., president and CEO
of Spire Sciences LLC, who performed the image analyses.
"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
JADA, included 301 patients with moderate-to-severe RA with
inadequate response to treatment with methotrexate.
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/STAT pathways. Additional
JAK-dependent cytokines also have been implicated in a number of
inflammatory and autoimmune diseases, suggesting that JAK
inhibitors may be useful for the treatment of a broad range of
inflammatory conditions.
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 December 2009, Lilly and Incyte
announced an exclusive worldwide license and collaboration
agreement for the development and commercialization of baricitinib
and certain follow-on compounds for inflammatory and autoimmune
diseases.
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.
About the Webcast
Lilly and Incyte are hosting an
investor meeting to discuss the baricitinib Phase II RA data
presented at ACR. The presentation will be webcast live at
7 p.m. ET on Nov. 13, 2012 and will be available as a replay
on both Lilly's website at http://investor.lilly.com/events.cfm and
Incyte's website at http://www.incyte.com/ under Investor
Relations, Events and Webcasts.
About Eli Lilly and Company
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 Indianapolis, Ind., Lilly provides answers –
through medicines and information – for some of the world's most
urgent medical needs. Additional information about Lilly is
available at http://www.lilly.com/.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization
of proprietary small molecule drugs for oncology and inflammation.
For additional information on Incyte, please visit the Company's
website at http://www.incyte.com/.
This press release contains certain forward-looking
statements about baricitinib as a potential treatment for patients
with rheumatoid arthritis and reflects Lilly and Incyte's current
beliefs. However, as with any pharmaceutical product, there are
substantial risks and uncertainties in the process of development
and commercialization. There is no guarantee that future study
results and patient experience will be consistent with study
findings to date or that the product will be commercially
successful. For further discussion of these and other risks and
uncertainties, see Lilly's and Incyte's filings with the United
States Securities and Exchange Commission. Lilly and Incyte
undertake no duty to update forward-looking statements.
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 European Congress of Rheumatology,
presented by the European League Against Rheumatism, Berlin, Germany, June
2012).
[2] Arthritis Foundation, What is Rheumatoid Arthritis,
http://www.arthritis.org/types-what-is-rheumatoid-arthritis.php
(Accessed: May 1, 2012).
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SOURCE Eli Lilly and Company; Incyte Corporation