On April 23, 2018 a meeting of the Arthritis Advisory Committee took place to review new drug application (NDA) 207924 sponsored by Eli Lilly and Company.
On April 23, 2018 a meeting of the Arthritis Advisory Committee took place to review new drug application (NDA) 207924 sponsored by Eli Lilly and Company. The new molecular entity, baricitinib, is a Janus associated kinase inhibitor proposed for the treatment of active rheumatoid arthritis in adults who have not had an appropriate response to methotrexate. Lilly proposed a 2 mg and 4 mg oral dose of baricitinib, to be taken once daily.
Rheumatoid arthritis can cause stiffness, functional impairment and pain. In most cases, the condition is chronic and progressive, with an increasing risk of morbidity and mortality as it progresses. Baricitinib acts as an immunosuppressant to treat the progression.
The sponsor presented 4 placebo- controlled, phase 3 trials supporting the efficacy of the 2 mg and 4 mg dose. Both doses were found to be effective. Committee members raised concerns over the safety profile of the 4 mg dose. Thus, the 2 mg dose had a more acceptable benefit/risk profile. Safety concerns included increased risk of infection, arterial and venous thrombosis, herpes zoster, various malignancies, liver test elevations and elevated platelet counts; which were all specific to the 4 mg dose.
The panel had 2 discussion questions and 4 voting questions regarding safety, efficacy and risk/benefit ratio for each dose of the drug. The panel voted: 14 (Yes) to 1 (No) on whether the 2 mg dose was shown to be efficacious, while voting: 15 (Yes) to 0 (No) on the efficacy of the 4 mg dose. Dr. Jon Russel explained that although the 2 mg dose was clinically efficacious, the radiographic assessment did not show any improvement.
The panel was then asked to assess the adequacy of the safety data for the 2 doses. The panel voted in support of the safety of the 2 mg dose: 9 (Yes) to 6 (No), while voting against the safety of the 4 mg dose, 5 (Yes) and 10 (No). Panelists expressed concern over the risk thromboembolic events.
The final 2 votes evaluated the benefit-risk profile of each dose, with the panel voting 10 (Yes) to 5 (No) for the 2 mg dose and 5 (Yes) and 10 (No) for the 4 mg dose. The panel members indicated that the drug should only be used if patients do not improve after using biologics; and asked for more data through a mandatory post marketing safety study.
The agency is not obligated to follow its panel’s recommendation, but normally does so. On June 1st, 2018, the FDA approved Olumiant (baricitinib) 2 mg oral tables for treatment of adults with moderate to severely active rheumatoid arthritis. The 4 mg dose was not approved.
ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact email@example.com
This post was authored by Sami Mourad. Sami is a summer intern at ISS and a 3rd year pharmacy student at the Rutgers University Ernest Mario School of Pharmacy
Over the past few years, the number of ex-US manufacturers submitting a Class II exempt 510k device registration has increased substantially. For companies with medical devices that are approved and successful in a foreign market, the logical next step is to introduce their product into the US, which has one of the most lucrative healthcare markets in the world. Read more
FDA advisory committee meetings are important regulatory events for many manufacturers on the path to marketing approval. These meetings can quite literally result in the approval or rejection of a product based on the panel’s vote. Read more
One of the main challenges our clients face is determining which regulatory pathway is best for their products. For example, what if an OTC product has a Monograph active ingredient but that ingredient is present at a different amount than the permitted amount? Or what if the label claims a novel indication not specified in a Monograph? If you are debating pursuit of either regulatory pathway for your OTC drug, it is critical to consider cost, timeline, and label claims to ensure your products has a unique stance in today’s market. Read more
US distributors and agents trying to import rapid antibody tests for coronavirus face a number of obstacles. The good news is that FDA has opened up the Emergency Use Authorization (EUA) program to include SARS-CoV-2 (the virus) and COVID-19 (the disease), expediting time to market. Read more
The journey to scientific and commercial success is often complex and always critical, if you are looking for an expert partner to help steer you to confident solutions, contact us todayContact us