Lilly’s Hopes For Tabalumab Now Rest In Lupus, Myeloma Settings
This article was originally published in The Pink Sheet Daily
Executive Summary
The company terminates all late-stage development of the anti-B cell antibody in rheumatoid arthritis due to lack of efficacy. Ongoing studies in lupus and multiple myeloma are expected to begin reporting in 2014.
Eli Lilly & Co.’s hopes for the future of tabalumab rest in the lupus and multiple myeloma settings now that the company has terminated all development for rheumatoid arthritis.
On Feb. 7, the company announced that it would stop all Phase II and Phase III studies of the anti-B cell activating factor monoclonal antibody in RA due to lack of efficacy. The RA program’s termination is expected to result in an approximately $50 million R&D expense charge in the first quarter, the company said.
The decision comes two months after Lilly suspended enrollment in the RA program due to a lack of efficacy in the FLEX-M study. That trial, which enrolled patients with moderate-to-severe RA who had an inadequate response to methotrexate therapy, was stopped after a planned interim analysis revealed insufficient efficacy (Also see "Lilly Antibody Proves Ineffective In Rheumatoid Arthritis, But Lupus Trials Continue" - Pink Sheet, 13 Dec, 2012.). The company subsequently conducted an interim futility analysis of the FLEX-V study, which enrolled patients with moderate-to-severe disease who had an inadequate response to one or more tumor necrosis factor inhibitors.
“We continue to believe that tabalumab could have significant potential for patients in other disease areas,” Lilly VP Roberts said.
“Based on the outcomes of these two separate interim futility analyses, Lilly has decided to discontinue development of tabalumab in the current RA program,” the company said in a press release.
In addition to the double-blind, placebo-controlled FLEX-M and FLEX-V studies, the company is stopping a Phase II open-label biomarker study, a Phase III open-label pharmacokinetic study comparing administration by auto injector or pre-filled syringe, and a Phase IIIb open-label extension study of long-term safety and efficacy.
Another Phase III double-blind study, FLEX-O, was evaluating tabalumab in RA patients with or without background disease-modifying anti-rheumatic drug therapy. The estimated final data collection date for the primary outcome measure in that study was December 2012, with final study completion expected a year later, according to ClinicalTrials.gov. Lilly said that FLEX-O is not being stopped as it has already completed treatment.
Discontinuation of the tabalumab program leaves baricitinib, a JAK1 and JAK2 inhibitor being developed with Incyte Corp., as Lilly’s only late-stage pipeline asset in RA.
During its most recent earnings call Jan. 29, Lilly executives expressed confidence in the company’s late-stage pipeline, even though they recently lost development partners for two compounds in oncology and diabetes (Also see "Lilly Puts Faith In Late-Stage Assets In Hopes Of Profit Growth In 2014" - Pink Sheet, 29 Jan, 2013.).
Lupus, Myeloma Programs Continue
Despite the pipeline setback in RA, Lilly believes tabalumab can find success in other disease settings.
“While we are obviously disappointed by these results in rheumatoid arthritis, we continue to believe that tabalumab could have significant potential for patients in other disease areas,” said Eiry Roberts, vice president of autoimmune product development. “Autoimmune disorders are highly individualized. We believe that targeting BAFF with a molecule such as tabalumab may still represent an important advance for patients, and therefore we will continue the ongoing Phase III tabalumab lupus program.”
That program encompasses two double-blind Phase III trials to evaluate the efficacy, safety and tolerability of two different doses of tabalumab in addition to standard of care in patients with active systemic lupus erythematosus.
The primary endpoint is the proportion of patients achieving an SLE Responder Index response at week 52. Total estimated enrollment for the two studies is 2,280 patients, and final data collection for the primary outcome measure is expected by July 2014, according to ClinicalTrials.gov. Subjects who have completed one of the two core studies may enroll in a Phase III, open-label extension study to assess long-term safety and efficacy.
Lilly also is continuing with its multiple myeloma program for tabalumab. This includes an ongoing, double-blind, placebo-controlled Phase II/III trial in combination with bortezomib (Takeda Oncology’s Velcade) and dexamethasone in previously treated patients.
The primary outcome measures in the 771-patient trial are the number of subjects with a given best objective myeloma response and progression-free survival. Final data collection for the primary outcome is slated for January 2014.