Lilly's Olumiant Resubmission Includes Safety Data From US FDA's Sentinel Network

Lilly used Reagan-Udall’s IMEDS to tap Sentinel for data on incidence of venous thromboembolism in patients with rheumatoid arthritis. 

Eli Lilly & Co. resubmitted an application to FDA for the rheumatoid arthritis candidate Olumiant (baracitinib) that includes safety information drawn from US FDA's Sentinel data network for postmarket medical product surveillance.

Lilly Senior Research Scientist Claudia Salinas discussed the relatively novel use of the data network during the annual Sentinel Public Workshop in Washington D.C. Feb. 7.

"Lilly launched a query to provide context about the safety profile of patients with RA who were receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs) and in particular, we were interested in estimating the incidence of venous thromboembolism in these patients," she explained. "The results from the query were included as part of Lilly's resubmission for baracitinib."

Lilly resubmitted the application for Olumiant, under development with Incyte Corp., in December 2017 after announcing a complete response letter from FDA in April. The agency sought additional data on the most appropriate dose for the drug and information on safety concerns that arose in the clinical trials. (Also see "Baricitinib Complete Response May Put Lilly/Incyte Behind IL-6 Blockers In RA" - Scrip, 14 Apr, 2017.)

There were two reported deaths among patients with pulmonary embolism events in the clinical trials on Olumiant, Lilly Bio-Medicines Senior VP and President Christi Shaw explained during the company's earnings call Jan. 31. One death occurred in the Olumiant group more than 500 days after the first dose and one occurred in the methotrexate group after more than 200 days of treatment.

Largest Treatment Group Included 69,000 Patients

The research using Sentinel involved five data partners with information covering 75 million individuals. The largest treatment group drawn from the data included 69,000 patients, Salinas noted. The data yielded venous thromboembolism incidence rates of 1.49 per 100 person years for new users of conventional DMARDS and 0.98 per 100 person years for new users of biologic DMARDs. The researchers also looked for incidences of pulmonary embolism and deep vein thrombosis.

Lilly used the Reagan-Udall Foundation's Innovation in Medical Evidence Development and Surveillance (IMEDS) program to tap the Sentinel data network and research team, which is based at the Harvard-Pilgrim Healthcare Institute. IMEDS is a public-private partnership established to function as an entry point for non-FDA researchers to use Sentinel.

"As I have spoken to rheumatologists who are treating these patients, there is interest in the results we have seen but they are not aware of this data source." – Lilly's Salinas

So far only a few pharmaceutical companies have engaged with IMEDS to conduct research in Sentinel. Pfizer Inc. is another; the company completed a pilot study using the research program in 2016. (Also see "Sentinel Offers Drug Firms ‘Unique’ Venue For Post-Market Studies, Pfizer Says" - Pink Sheet, 5 Feb, 2017.)

 Lilly researchers worked extensively with the Sentinel experts in developing the specific query that would be applied to the database. "We needed to actually get … most of the details defined ahead of time so we could decide the scope of the work" including the various scenarios that would be explored for each treatment group, she said. "This step was probably the biggest learning curve, especially for people who have not worked with the Sentinel team before. We also had to learn about the limitations of the tool."

In designing the research, Harvard-Pilgrim researchers also did a feasibility assessment to see if there were "any scenarios that we wanted to eliminate or that wouldn't be practical" but "we chose to be blinded for this so that the results of the incidence rate wouldn't affect what we retained or removed," Salinas said. Lilly then sent the final specifications back to Harvard-Pilgrim and "a few weeks later we had our results."

Research Parameters Can Be Used By Others To Replicate Results

The company selected the IMEDS data for two reasons, Salinas said. "The first was size. Because we were looking for a rare outcome we needed a large data source. And the second was the existence of validated tools for conducting the query."

Furthermore, she continued, "having validated programs that are sort of 'hands off' – n that you define parameters ahead of time and anybody starting with your parameters will get the same results – is very reassuring both to industry and I'm sure, to regulators. So that is another strength of this data."

Salinas recommended that IMEDs expand access and public awareness of its program. "In particular, as I have spoken to rheumatologists who are treating these patients, there is interest in the results we have seen but they are not aware of this data source," she said.