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

Pfizer RA Drug Meets Study Goals

We knew that,  Tofacitinib (see structure, formerly tasocitinib is a drug being investigated by Pfizer for the treatment of rheumatoid arthritis (RA), psoriasis,inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection. It is an inhibitor of the enzyme Janus kinase 3 (JAK3), which means that it interferes with the JAK-STAT signaling pathway that transmits information outside the cell into the cell nucleus, influencing DNA transcription.

Now Pfizer now claims that the drug has   met its key goals of reducing signs and symptoms of the condition in separate studies on patients over a 12-month and six-month period. Rheumatoid arthritis is a chronic inflammatory disease typically affecting joints.

The company's Oral Standard study involved 717 patients over a 12-month period with moderate-to-severe rheumatoid arthritis who had an inadequate response to the drug methotrexate. Meanwhile, the Oral Step study involved 399 patients over a six-month period with moderate-to-severe rheumatoid arthritis who did not have an adequate response to TNF inhibitor drugs.  Pfizer said no new safety signals emerged in the Oral Standard and Oral Step studies. A more detailed analysis off the data will be submitted to a future scientific meeting. 

The most common side effects of treatment with tofacitinib have included bronchitis, headache, infections, and gastrointestinal symptoms like nausea, vomiting, and diarrhea. More serious side effects in a mid-stage trial included lower levels of a type of white blood cell called neutrophils, higher cholesterol levels and increased creatinine levels.

Tofacitinib is a key developing drug for Pfizer and is also being studied as a potential treatment for psoriasis, inflammatory bowel disease, and renal transplant. A topical version of the drug is being studied as a psoriasis treatment and a dry eye disease treatment....

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