FDA Advisory Committee Recommends the Approval of Baricitinib 2mg, but not 4mg, for the Treatment of Moderately-to-Severely Active Rheumatoid Arthritis

Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) announced  that the U.S. Food and Drug Administration's (FDA) Arthritis Advisory Committee recommended approval of the 2-mg dose of baricitinib, a once-daily oral medication for the treatment of moderately-to-severely active rheumatoid arthritis (RA) for adult patients who have had an inadequate response or intolerance to methotrexate. While the Advisory Committee unanimously supported the efficacy of the 4-mg dose of baricitinib, it did not recommend approval of the 4-mg dose of baricitinib for the proposed indication based on the adequacy of the safety and benefit-risk profiles.

"We are confident that baricitinib, if approved, can help people in the U.S. manage the challenges of living with RA," said Christi Shaw, president of Lilly Bio-Medicines. "While we are disappointed with the Advisory Committee's assessment of the data for the 4-mg dose, we are confident in the positive benefit-risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application (NDA) and are hopeful that baricitinib will receive approval in the coming months."

Baricitinib 2-mg and 4-mg doses are approved in more than 40 countries, including the member states of the European Union and Japan.

For both doses, the Advisory Committee voted to support the assessment that baricitinib's data provide substantial evidence of efficacy. For the 2-mg dose, the Advisory Committee voted in favor of the assessment that baricitinib's safety data adequately support its approval. For the 4-mg dose, the Advisory Committee voted against the assessment that baricitinib's safety data was adequate to support its approval based on the proposed indication.

The Advisory Committee's recommendation was based on baricitinib's global development program, which included four completed Phase 3 studies. In total, 3,492 patients, who represented a range of treatment experiences, received baricitinib in the global RA development program. The Phase 3 studies evaluated baricitinib's treatment impact related to RA signs and symptoms, physical function, joint damage progression and other patient-reported outcomes. The Phase 3 program also evaluated recognized risks for RA patients, including serious infection, malignancy, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and gastrointestinal perforations, along with key laboratory changes. The safety profile of baricitinib is based on 7,860 patient-years of exposure.

"Despite advances in the management of RA over the last 20 years, which include early treatment, optimized use of traditional therapies for rheumatic disease and the advent of newer medications such as biologics, many patients are still struggling to meet treatment targets, and live with debilitating pain, fatigue and other symptoms of RA," said Peter Taylor, MA, PhD, professor, University of Oxford, an expert who attended the Advisory Committee Meeting. "Baricitinib could be a promising option for RA patients in the U.S. who are not achieving adequate disease control with currently available treatments."

The FDA is not required to follow the Advisory Committee's recommendation, but will consider it during its review of the NDA for baricitinib.

FDA Advisory Committee Recommends the Approval of Baricitinib 2mg, but not 4mg, for the Treatment of Moderately-to-Severely Active Rheumatoid Arthritis

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19

In continuation of my update on baricitinib and remdesivir

Emergency use authorization was issued for baricitinib in combination with remdesivir for hospitalized patients with COVID-19, the U.S. Food and Drug Administration announced Thursday.

                               

The EUA for the combination treatment applies to hospitalized patients ages 2 years and older with suspected or laboratory-confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. The janus kinase inhibitor baricitinib is currently FDA-approved for treating moderately to severely active rheumatoid arthritis.

Based on the agency's review of the evidence, the FDA "determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population. And, when used under the conditions described in the EUA to treat COVID-19, the known and potential benefits of baricitinib outweigh the known and potential risks for the drug."

The FDA granted the EUA based on data from the ACTT-2 trial, a randomized, double-blind, placebo-controlled clinical trial conducted by the National Institute of Allergy and Infectious Diseases. The trial included 1,033 patients -- 515 randomly assigned to baricitinib plus remdesivir and 518 randomly assigned to placebo plus remdesivir. Patients were followed for 29 days. Median time to recovery from COVID-19 was seven and eight days for patients receiving baricitinib plus remdesivir and those receiving placebo plus remdesivir, respectively. Patients receiving baricitinib plus remdesivir had significantly lower odds of progressing to death or being ventilated at 29 days and significantly higher odds of clinical improvement at 15 days compared with patients receiving placebo plus remdesivir.

Baricitinib is not authorized or approved as a stand-alone treatment for COVID-19, the FDA notes. Its safety and effectiveness for use in the treatment of COVID-19 continue to be evaluated.

https://en.wikipedia.org/wiki/Baricitinib

https://en.wikipedia.org/wiki/Remdesivir

FDA Issues EUA to Baricitinib Plus Remdesivir for COVID-19  

FDA Approves Olumiant (baricitinib) 2 mg Tablets for the Treatment of Adults with Moderately-to-Severely Active Rheumatoid Arthritis

Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) announced today that the U.S. Food and Drug Administration (FDA) has approved the 2-mg dose of Olumiant (baricitinib), a once-daily oral medication for the treatment of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) inhibitor therapies.  Use of Olumiant in combination with other Janus kinase (JAK) inhibitors or biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.  Olumiant may be used as monotherapy or in combination with methotrexate (MTX) or other non-biologic DMARDs.

"We are pleased to provide RA patients in the U.S. an effective treatment option with Olumiant, as people with RA who have had an inadequate response to TNF inhibitors are generally considered to be some of the most difficult to treat RA patients," said Christi Shaw, president, Lilly Bio-Medicines.

The Olumiant clinical trial program included the RA-BEACON study, a randomized, double-blind, placebo-controlled study in which patients were randomly assigned to receive Olumiant 2 mg, baricitinib 4 mg or placebo, in addition to conventional DMARDs that they were currently using.  This study included 527 patients who had an inadequate response or intolerance to one or more TNF inhibitor therapies.  Patients could have had prior therapy with other bDMARDs. 

The study results showed that significantly higher ACR20 response rates and improvement in all individual ACR20 component scores were observed at Week 12 with Olumiant.1 The study found that patients treated with Olumiant had significantly higher rates of ACR20 response versus placebo-treated patients at Week 12 (49% of Olumiant-treated patients versus 27% of placebo-treated patients).1Olumiant also demonstrated early symptom relief, with ACR20 responses seen as early as Week 1.1Patients treated with Olumiant reported significant improvements in physical function based on the Health Assessment Questionnaire Disability Index (HAQ-DI) (recording an average score of 1.71 before treatment and 1.31 at Week 12) compared to placebo-treated patients (who recorded an average score of 1.78 before treatment and 1.59 at Week 12). 

Olumiant is approved with a Boxed Warning for the risk of serious infections, malignancies and thrombosis. Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving Olumiant. Lymphoma and other malignancies have been observed in patients treated with Olumiant as well. Additionally, thrombosis, including deep venous thrombosis, pulmonary embolism and arterial thrombosis, some fatal, have occurred in patients treated with Olumiant.  Other warnings and precautions include gastrointestinal perforations, laboratory abnormalities (including neutropenia, lymphopenia, anemia, liver enzyme elevations, and lipid elevations) and a warning against the use of live vaccines with Olumiant.  The most common adverse events (occurring in greater than or equal to 1% of Olumiant 2 mg- and baricitinib 4 mg-treated patients in placebo-controlled trials) included upper respiratory tract infections, nausea, herpes simplex and herpes zoster. 

As part of the approval, the companies have agreed to conduct a randomized controlled clinical trial to evaluate the long-term safety of baricitinib in patients with rheumatoid arthritis.

"Despite the advancements we've seen in the RA treatment landscape over the past several decades, many patients are still failing to achieve their disease management goals," said Seth Ginsberg, co-founder and president of CreakyJoints and the Global Healthy Living Foundation. "As it's important for RA patients to have multiple treatment options available to best suit their disease characteristics and experiences, the approval of Olumiant is very encouraging for our community."

RA is a chronic, painful and progressive form of arthritis  It is estimated that about two-thirds of established RA patients will not reach clinical remission with their first TNF inhibitor therapy, and a significant percentage will not maintain efficacy as time goes on. 

"In my clinical practice, I continue to see patients who experience debilitating symptoms and who are waiting for a medicine that may be right for them," said Elizabeth L. Perkins, M.D., Rheumatology Care Center, Birmingham, Alabama. "Olumiant is an important option for rheumatologists to help address these patients' unmet needs."

"RA patients continue to experience unique challenges accessing the treatments prescribed by their healthcare providers. Therefore, we are determined to continue our work with stakeholders to demonstrate value across the healthcare system so providers have greater choice in prescribing treatments to fit individual patient needs," said Shaw.

Lilly will launch Olumiant in the U.S. by the end of the second quarter of 2018. The price of Olumiant will be 60% less than the leading TNF inhibitor.5 Lilly will be offering a patient support program, Olumiant Together™. For more information about this program, please call 1-844-Olumiant.

Incyte is now eligible to receive a $100 million milestone payment from Lilly as a result of the Olumiant approval, which Incyte expects to recognize in the second quarter of 2018.