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Eli Lilly and Incyte face a roughly 18-month application delay for rheumatoid arthritis drug, baricitinib, in the US with a request from FDA for additional clinical data.
On July 25, 2017, Eli Lilly and Company and its partner, Incyte, announced that a resubmission to FDA for the new drug application (NDA) for baricitinib, a once-daily oral medication for treating moderate-to-severe rheumatoid arthritis (RA), will be delayed beyond 2017. The companies will be further discussing the path forward with the agency and evaluating options for resubmission, including the potential for an additional clinical study, as requested by FDA.
The length of time to a resubmission for the NDA will depend on which option the companies pursue and further FDA discussions, but is anticipated to be a minimum of 18 months. FDA has indicated that a new clinical study is necessary for a resubmission to further characterize the benefit/risk across doses of the drug, in light of an observed imbalance in thromboembolic events that occurred during a placebo-controlled period of the RA clinical program. The request for an additional clinical study does not impact the ongoing clinical trials for baricitinib.
Christi Shaw, president of Lilly Bio-Medicines, said in a company press release: “We disagree with the FDA's conclusions, and believe the existing comprehensive clinical data demonstrate there is a positive benefit/risk profile that supports baricitinib's approval as a new treatment option for people suffering from RA in the United States. We are disappointed that resubmission will not occur this year, but are committed to bringing baricitinib to people with RA and we will work with the FDA on the path forward."
The NDA for RA contained the results of four positive Phase III clinical trials that met their primary endpoints and in which 3100 patients were enrolled across the full spectrum of RA patients, from treatment-naïve to highly treatment refractory. Thromboembolic events, such as deep venous thrombosis (DVT) and pulmonary embolism (PE), were reported in five patients receiving baricitinib during the controlled period of two out of seven completed Phase II or Phase III trials in RA. Although an imbalance was observed during the placebo-controlled period of the RA clinical trials, the rate of these events in the overall baricitinib clinical program was consistent with that seen among the general population of treated RA patients, according to Lilly in a company press release.
In the European Union, where baricitinib 2-mg and 4-mg tablets have been approved since February 2017, the EMA’s Committee for Medicinal Products for Human Use recently agreed to update the label with a precaution for patients who have risk factors for DVT and PE. The label for the drug in Japan, where it was also recently approved in July 2017, includes a similar precaution.
This delay follows an earlier stumbling block for Lilly and Incyte when, in April 2017, FDA issued a Complete Response Letter (CRL) on the baricitinib NDA. The CRL indicated that FDA would not be able to approve the application in its then current form and that the agency was seeking additional clinical data to determine the most appropriate doses of the drug and to further characterize safety concerns across treatment arms.
Baricitinib, a once-daily oral Janus kinase (JAK) inhibitor, is currently in clinical studies for inflammatory and autoimmune diseases. 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, including RA.
Lilly and Incyte entered into an exclusive worldwide license and collaboration agreement in December 2009 to develop and commercialize baricitinib. The agreement also includes certain follow-on compounds for patients with inflammatory and autoimmune diseases. Baricitinib was submitted for regulatory review seeking marketing approval for treating RA in the US, EU, and Japan in 2016. In addition to approvals in the EU and Japan, baricitinib was also approved in Kuwait and Switzerland in June 2017 in the RA indication and remains under review in other markets. It is also being studied in Phase II trials for atopic dermatitis and systemic lupus erythematosus. A Phase III trial for psoriatic arthritis has been delayed and will not begin in 2017 as previously expected.
Source: Eli Lilly and Company