Baricitinib Superior to Methotrexate in Reducing Signs and Symptoms in Pivotal Phase 3 Study in Patients with Rheumatoid Arthritis

OREANDA-NEWS. October 01, 2015. 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 na?ve 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.

About Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease^[i] characterized by inflammation and progressive destruction of joints.^[ii] More than 23 million people worldwide suffer from RA.^[iii] Approximately three times as many women as men have the disease. Patients and physicians indicate there remains an important opportunity to improve patient care. Current treatment of RA includes the use of non-steroidal anti-inflammatory drugs, oral disease-modifying anti-rheumatic drugs such as methotrexate, and injectable biological response modifiers that target selected mediators implicated in the pathogenesis of RA.^[iv]

About Baricitinib Phase 3 Trials

Lilly and Incyte are conducting four pivotal Phase 3 clinical trials of baricitinib in patients with moderately-to-severely active rheumatoid arthritis to support regulatory submission in most countries. An additional Phase 3 study was initiated to support clinical development in China. The clinical trial program includes a wide range of patients including those who are methotrexate na?ve, inadequate responders to methotrexate, inadequate responders to conventional disease-modifying anti-rheumatic drugs, or inadequate responders to TNF inhibitors. Four of these five pivotal studies are expected to be completed by the end of 2015. Patients completing any of the five Phase 3 studies can enroll in a long-term extension study. For additional information on this clinical trial program, please visit www.clinicaltrials.gov.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical company focused on the discovery, development and commercialization of proprietary therapeutics for oncology and inflammation. For additional information on Incyte, please visit the Company's web site at www.incyte.com.

About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and newsroom.lilly.com/social-channels. (P-LLY)

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) 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 will be consistent with study findings to-date, or that baricitinib will receive regulatory approvals or prove to 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. Except as required by law, Lilly and Incyte undertake no duty to update forward-looking statements to reflect events after the date of this release.

^[i]American College of Rheumatology, Rheumatoid Arthritis, http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/ra.asp (Accessed: October 27, 2014)

^[ii]Hand Clinics, Advances in the Medical Treatment of Rheumatoid Arthritis, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135413/pdf/nihms305780.pdf (Accessed: October 27, 2014)

^[iii] WHO Global Burden of Disease Report, (table 7, page 32) 2004, http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf (Accessed Nov. 11, 2014)

^[iv]Arthritis Foundation, Medications for Rheumatoid Arthritis, http://www.arthritistoday.org/about-arthritis/types-of-arthritis/rheumatoid-arthritis/treatment-plan/medication-overview/ra-medications.php (Accessed: May 15, 2013)