Biotechnology Events

Home

Incyte Corporation

Partner : Eli Lilly

.

PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.

.

RA-BEGIN - A Randomized, Double-Blind, Active-Controlled,Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had Limited or No Treatment With Disease-Modifying Antirheumatic Drugs
Estimated Enrollment: 550
Study Start Date: November 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
More
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01711359?term=Baricitinib&rank=1

.

Compound/DeviceSpecialtyIndicationCompound ClassTarget
Baricitinib (INCB-28050) (LY3009104) RARheumatologyRheumatoid Arthritis (RA)Janus-associated Kinase InhibitorsJanus -associated Kinase

Mechanism of action: Baricitinib (INCB-28050) is a SM-inhibitor, reduces inflammation by disrupting the signaling of IL-6, IL-12, and IL-23 through the Janus-associated kinases (JAK) signaling pathway.

Phase of Development: III

Event Type: Data: Phase III trial results

Dates: 2015-02-01 - 2015-05-31

Results:

.

Patient-reported outcomes across phase 3 studies of baricitinib demonstrate statistically significant improvements in physical function and quality of life symptoms in patients with rheumatoid arthritis (RA)
Pivotal trials show treatment with baricitinib resulted in significant improvements in pain, fatigue and ability to perform daily activities compared to methotrexate - the current standard of care - and adalimumab (Humira®)*

INDIANAPOLIS, June 9, 2016 /CNW/ -- Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today announced that in two phase 3 trials patients with rheumatoid arthritis (RA) treated with baricitinib reported significant improvements in quality of life symptoms and other patient-reported outcomes compared to methotrexate or adalimumab (Humira®). Patients with RA also reported improvement in productivity at work. In these studies, significant improvements in patient-reported measures, including pain, physical function, tiredness and morning joint stiffness, were observed as early as one week after initial treatment with baricitinib. These findings were presented today at the Annual European Congress of Rheumatology (EULAR 2016) in London.
Key findings include:
In the phase 3 RA-BEGIN trial:
At 24 weeks, 81 percent of patients receiving baricitinib monotherapy and 79 percent of patients receiving baricitinib plus methotrexate had clinically meaningful improvement in physical function compared with 70 percent among those receiving methotrexate alone (p < 0.05). Clinically meaningful improvement was defined as an improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) score of ≥0.22.
At 52 weeks, 68 percent of patients on baricitinib monotherapy and 72 percent of patients on baricitinib in combination with methotrexate saw clinically meaningful improvements in physical function compared to 57 percent of those treated with methotrexate alone (p < 0.05).
At 24 and 52 weeks, baricitinib (as monotherapy or in combination with methotrexate) was also associated with significant improvement in pain, and clinically meaningful improvement in fatigue and the physical health components of the quality of life assessment compared with methotrexate alone.
In the phase 3 RA-BEAM trial, where all patients received background methotrexate therapy:
At 12 weeks, 75 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 71 percent of patients on adalimumab (p=0.302). Clinically meaningful improvement was defined as an improvement in HAQ-DI score of ≥0.22.
At 24 weeks, 73 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 64 percent of patients on adalimumab (p < 0.05).
At 52 weeks, 68 percent of patients treated with baricitinib reported clinically meaningful improvement in physical function compared with 58 percent of patients on adalimumab (p < 0.01).
At 52 weeks, baricitinib was also associated with significant improvement in pain, and clinically meaningful improvement in fatigue and the physical health components of quality of life compared with adalimumab.
An analysis of the phase 3 trials found that in each study, patients taking baricitinib have less impairment in work productivity and daily activities compared to patients taking the comparator.
"Our extensive phase 3 clinical trial program demonstrates that baricitinib could, if approved, offer a potentially significant improvement in the treatment of rheumatoid arthritis," said Terence Rooney, M.D., medical director, rheumatoid arthritis, Lilly Bio-Medicines. "In these studies, baricitinib demonstrated superiority on a variety of efficacy measures compared to the leading biologic, adalimumab, as well as the current oral standard of care, methotrexate. Additionally, patients reported their personal experience with baricitinib, further highlighting its positive impact on patients' daily lives and activities."
Physical function was measured using the patient-reported HAQ-DI questionnaire that assesses the ability of a patient to perform daily activities like dressing, eating, walking, grip, etc. Quality of life assessment was made by using the Medical Outcomes Study 36-Item Short Form Health Survey Version 2 Acute, or SF-36, which is a patient-reported survey that measures overall health quality based on physical and psychological functioning.
RA-BEGIN demonstrated that in RA patients who had limited or no previous treatment with any disease-modifying antirheumatic drugs (DMARDs), baricitinib used as monotherapy or in combination with methotrexate showed statistically significant improvements in the physical quality of life measures, as measured by the SF-36, when compared to methotrexate alone. Reported improvements in patient quality of life symptoms were accompanied by an increase in physical function, and decreased pain and fatigue. All the improvements with baricitinib were statistically significant at week 24 and week 52, compared to methotrexate alone.
The RA-BEGIN study included patients who had limited or no prior treatment with methotrexate, and were naïve to other conventional or biologic DMARDs. Part of a larger phase 3 program of more than 3,000 RA patients at various points in the RA treatment continuum, RA-BEGIN enrolled nearly 600 patients who were randomized to one of the following treatment groups:
Once-weekly oral methotrexate monotherapy
4 mg once-daily oral baricitinib monotherapy
4 mg once-daily oral baricitinib in combination with once-weekly oral methotrexate.
"Left untreated or uncontrolled, rheumatoid arthritis can dramatically impact patients' quality of life," said Steven Stein, M.D., chief medical officer, Incyte Corporation. "Patients and physicians alike deserve better treatment options beyond today's standard of care. If approved, baricitinib has the potential to become an oral drug option that may improve the clinical symptoms of the disease, as well as patients' ability to perform daily activities at home and at work."
The pivotal phase 3 trial, RA-BEAM, showed that RA patients who had previously responded inadequately to methotrexate and were not treated with any biologic, experienced significant improvement in the physical quality of life measures when taking baricitinib compared to patients treated with adalimumab or placebo. Reported improvements in patient quality of life were accompanied by an increase in physical function, and decreased pain and fatigue. The improvements in physical function, pain and physical quality of life with baricitinib were statistically significant at week 24 and week 52, compared to adalimumab.
RA-BEAM was a 52-week trial of 1,305 patients who had active, moderate-to-severe RA, despite ongoing treatment with methotrexate. Patients were randomized to placebo once-daily (n=488), baricitinib 4 mg once-daily (n=487) or adalimumab 40 mg biweekly (n=330). All patients received background methotrexate. At week 24, patients taking placebo were crossed over to the baricitinib treatment group.
In the baricitinib RA development program, no increases in adverse events leading to study drug discontinuation, malignancies, or serious infections were seen for baricitinib vs. placebo or active comparators during the controlled periods of the program. Herpes zoster was reported more frequently for baricitinib vs. placebo. The incidence rates of malignancy, serious infection and herpes zoster did not increase over time including long-term observations.
More
Source: press release, 6/09/16. http://www.incyte.com/ir/press-releases.aspx

.

Lilly and Incyte Announce Patients Treated with Baricitinib Demonstrated Significant Improvement in Signs and Symptoms of Rheumatoid Arthritis Compared with Methotrexate
- Compared to methotrexate, baricitinib as monotherapy or in combination with methotrexate demonstrated improvements in all ACR components as early as week 1 and maintained through 52 weeks

- Both baricitinib regimens were superior to methotrexate monotherapy in inducing clinical remission, using measures such as SDAI, at weeks 24 and 52

- Baricitinib plus methotrexate also demonstrated significant inhibition of progressive radiographic structural joint damage measured using van der Heijde modified Sharp Score versus methotrexate alone at weeks 24 and 52

INDIANAPOLIS, Nov. 7, 2015 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today announce detailed data from the pivotal phase 3 RA-BEGIN study, which show investigational baricitinib alone and in combination were superior to methotrexate monotherapy in helping patients achieve clinical remission. Findings will be shared at the American College of Rheumatology /Association of Rheumatology Health Professionals annual meeting in San Francisco, revealing superiority for investigational therapy baricitinib over methotrexate in improving multiple measures of the signs and symptoms of rheumatoid arthritis.

Lilly and Incyte previously announced that the study met its primary objective of demonstrating the non-inferiority of baricitinib monotherapy to methotrexate monotherapy based on ACR20 response rate after 24 weeks of treatment. Additionally, it was announced that baricitinib was superior to methotrexate based on ACR20 response.

"Left untreated or uncontrolled, RA can progress and significantly impact long-term health, career and quality of life," said Roy Fleischmann, M.D., lead study author and clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas. "If it gains FDA approval, baricitinib could be a new choice for us to turn to, especially for patients who cannot take methotrexate."

In the RA-BEGIN trial, 584 patients who had limited or no prior treatment with methotrexate and who had never received other conventional or biologic disease-modifying antirheumatic drugs (DMARDs) were randomized to methotrexate once weekly (n=210), baricitinib 4 mg once daily (n=159) or baricitinib daily in combination with methotrexate weekly (n=215) for up to 52 weeks. The weekly methotrexate dose was increased from 10 mg to 20 mg over 8 weeks.

Improvements compared to methotrexate were seen for baricitinib alone or in combination with methotrexate as early as week 1 for all components of the ACR response (swollen and tender joint counts, pain, patient and physician global assessment of disease activity and physical function). These improvements were maintained at weeks 24 and 52.

Baricitinib plus methotrexate also demonstrated significant inhibition of progressive radiographic joint damage versus methotrexate alone in RA-BEGIN, the third phase 3 study of baricitinib in RA to show this finding.

"Reaching clinical remission as soon as possible is important to help prevent irreversible joint damage that could lead to disability," said Terence Rooney, M.D., medical director, rheumatoid arthritis, Lilly Bio-Medicines. "These positive results for baricitinib add to the growing body of evidence supporting this balanced JAK1 and JAK2 inhibitor as a potential new once-daily oral treatment option for people living with active RA."

The incidence of treatment-emergent adverse events and serious adverse events, including serious infections, was similar across treatment groups through week 52. No cases of tuberculosis or spontaneous gastrointestinal perforation were reported during the study. The most common adverse events observed were consistent with previous studies of baricitinib in RA. Compared to methotrexate, baricitinib monotherapy was associated with lower rates of liver abnormalities, lymphopenia and adverse events leading to interruption, while the combination of baricitinib plus methotrexate was associated with increases in non-serious infections and adverse events leading to permanent discontinuation.

"A significant medical need remains in the RA community as patients respond differently to different treatments," said Rich Levy, M.D., chief drug development officer of Incyte. "We are very pleased with the results of the phase 3 RA-BEGIN study, which show superiority of baricitinib over methotrexate, a commonly used treatment for early RA, and demonstrate baricitinib's promise as a potential new treatment option that offers patients improved disease control."

Lilly and Incyte announced top-line results in December 2014 for the first phase 3 trial of baricitinib, RA-BEACON, in February 2015 for the second, RA-BUILD, in September 2015 for the third, RA-BEGIN and in October 2015 for the fourth, RA-BEAM. The companies will also share detailed results from the RA-BEAM study at ACR this year and plan to submit additional detailed data from all four studies for presentation in scientific meetings and publication in peer-reviewed journals in 2016.

About Baricitinib
Baricitinib is the only once-daily oral selective JAK1 and JAK2 inhibitor currently in late-stage clinical studies for inflammatory and autoimmune diseases. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions. Baricitinib demonstrates approximately 100-fold greater potency of inhibition against JAK1 and JAK2 than JAK 3 in kinase assays.

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 patients with inflammatory and autoimmune diseases. Baricitinib is currently in phase 3 clinical development for rheumatoid arthritis and phase 2 development for psoriasis, diabetic nephropathy and atopic dermatitis.
More
Source: press release, 11/07/15. http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=2...

.

Baricitinib Superior to Methotrexate in Reducing Signs and Symptoms in Pivotal Phase 3 Study in Patients with Rheumatoid Arthritis
INDIANAPOLIS, Sept. 29, 2015 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) today announced positive top-line results of RA-BEGIN, the third Phase 3 study evaluating the safety and efficacy of baricitinib, an investigational medicine for patients with moderately-to-severely active rheumatoid arthritis (RA). The study met its primary objective of demonstrating non-inferiority of baricitinib monotherapy to methotrexate monotherapy based on ACR20 response rate after 24 weeks of treatment. Additionally, baricitinib was superior to methotrexate based on ACR20 response.

"Too many people with rheumatoid arthritis who are treated with methotrexate – commonly used across the disease continuum for 25 years – do not achieve adequate disease control, which can cause disability and impede productivity," said David Ricks, Lilly senior vice president, and president of Lilly Bio-Medicines. "People living with RA who achieve adequate disease control can be more active with their families, in their careers and in their communities – emphasizing the importance of effective treatment options."

The RA-BEGIN study included patients who had limited or no prior treatment with methotrexate, and were naïve to other conventional or biologic disease-modifying antirheumatic drugs (DMARDs). Part of a larger Phase 3 program of more than 3,000 RA patients at various points in the RA treatment continuum, RA-BEGIN enrolled nearly 600 patients who were randomized to one of the following treatment groups:

Once-weekly oral methotrexate monotherapy
4 mg once-daily oral baricitinib monotherapy
4 mg once-daily oral baricitinib in combination with once-weekly oral methotrexate
"The superiority of baricitinib over methotrexate in the treatment of patients with early RA adds to the positive data already seen for baricitinib in RA patients with inadequate responses to traditional DMARDs (RA-BUILD) and biological therapies (RA-BEACON)," said Rich Levy, M.D., chief drug development officer of Incyte. "The sum of these results further illustrates the therapeutic profile of baricitinib. If approved, we believe that baricitinib has the potential to be used across multiple lines of therapy in rheumatoid arthritis."

In RA-BEGIN, the incidence of treatment-emergent adverse events and serious adverse events, including serious infections, was similar across treatment groups. No cases of tuberculosis or gastrointestinal perforation were reported during the study. The most common adverse events observed were consistent with previous studies of baricitinib in RA. Discontinuations due to adverse events were more common in patients receiving the combination of baricitinib plus methotrexate. A large majority of patients completing RA-BEGIN opted to participate in a long-term extension study.

Lilly and Incyte announced top-line results in December 2014 for the first Phase 3 trial of baricitinib, RA-BEACON, and in February 2015 for the second, RA-BUILD. Data from these studies were presented at the EULAR annual scientific congress in June 2015. The companies plan to submit additional detailed data from all three of these studies for presentation in scientific meetings and publication in peer-reviewed journals in 2015 and 2016. Topline results of the fourth Phase 3 study, RA-BEAM, are expected later this year.

About Baricitinib
Baricitinib is a once-daily, oral, selective JAK1 and JAK2 inhibitor. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions. Baricitinib demonstrates approximately 100-fold greater potency of inhibition against JAK1 and JAK2 than JAK 3 in kinase assays.

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 patients with inflammatory and autoimmune diseases. Baricitinib is currently in Phase 3 clinical development for rheumatoid arthritis and Phase 2 development for psoriasis and diabetic nephropathy.
More
Source: press release, 9/29/15. http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=2...

.