Lilly Antibody Proves Ineffective In Rheumatoid Arthritis, But Lupus Trials Continue
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
Lilly has stopped one Phase III rheumatoid arthritis trial for its anti-BAFF antibody tabalumab and ceased enrollment in two others after a mid-term analysis revealed a lack of efficacy, but the company is soldiering on with a Phase III program in lupus erythematosus.
Eli Lilly & Co. is re-evaluating its anti-B cell activating factor antibody tabalumab in rheumatoid arthritis after the first of three ongoing Phase III trials was stopped for futility, but studies in lupus erythematosus will continue to enroll patients, the company announced Dec. 13.
The FLEX-M trial in RA was stopped after an interim analysis revealed insufficient efficacy.
The FLEX-M trial, in patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate therapy, was stopped after a planned interim analysis revealed insufficient efficacy. No safety concerns were revealed, and treatment will continue for patients in two other Phase III rheumatoid arthritis trials: FLEX-V, in patients with an inadequate response to a tumor necrosis factor inhibitor, and an unnamed long-term open-label study. However, no new patients will be added until an analysis from other ongoing rheumatoid arthritis studies is completed in early 2013, the company said.
Phase III trials testing tabalumab against systemic lupus erythematosus will continue as planned. There is no evidence to suggest efficacy results for rheumatoid arthritis are indicative of how the drug will perform in lupus, and “Lilly remains committed to the ongoing Phase III lupus program,” the company said. The lupus trials are expected to yield data in mid-2014.
With tabalumab in lupus, Lilly is looking to challenge GlaxoSmithKline PLC’s Benlysta (belimumab), a first in class antibody inhibitor of the B-lymphocyte stimulator (BLyS), which won approval in March 2011 (Also see "HGSI/GSK's Benlysta Gets BLySfully Clean Labeling, Escaping Feared Restrictions" - Pink Sheet, 10 Mar, 2011.).
Benlysta was the first new therapy for lupus erythematosus in half a century, but its launch has been a slog for GSK, which acquired former partner and Benlysta originator Human Genome Sciences Inc. in July 2012 (Also see "Benlysta In GSK’s Hands: A Slow-but-steady Launch, Or A Dud?" - Pink Sheet, 23 Jul, 2012.).
If Lilly can get tabalumab through Phase III and clearly differentiate its advantages over its struggling opponent, it could reap the market share Glaxo was going for with Benlysta. Glaxo has called the slow uptake a problem of education, with physicians and patients unclear regarding the therapy’s benefits against such a notoriously heterogeneous disease.
Lilly’s Other Autoimmune Bets
Tabalumab (LY 2127399) was the first molecule to pass from Lilly’s virtual, fast-track research and development unit Chorus into Phase III testing (Also see "Inside Lilly Research Laboratories: A Discussion With Jan Lundberg" - In Vivo, 1 Nov, 2010.).
To date Chorus, which was established in 2002 to cut the costs and time it takes to develop new drugs, has delivered data on 17 molecules, six of which have resulted in positive proof-of-concept clinical data, according to Lilly. The global, early phase drug development network is focused on progressing potential therapies from candidate selection to clinical proof of concept (Also see "Lilly's Chorus Experiment" - In Vivo, 1 May, 2007.).
Another home-grown molecule, ixekizumab (LY2439821), an interleukin 17-A (IL-17) blocker, is in Phase III testing against psoriasis and psoriatic arthritis. Both UNCOVER-2 and UNCOVER-3, comparing ixekizumab against etanercept (Amgen Inc./Pfizer Inc.’s Enbrel), are recruiting psoriasis patients, while SPIRIT-P1 is not yet recruiting patients for a study against psoriatic arthritis with a placebo comparator.
IL-17 blockers are set to be the next class of biologics to test the autoimmune market, and ixekizumab is competing against Novartis AG’s secukinumab, which has Phase III data in plaque psoriasis due in 2013, and Amgen/AstraZeneca PLC’s brodalumab, which began the AMAGINE-2 and -3 Phase III trials comparing brodalumab against ustekinumab (Johnson & Johnson’s Stelara) in patients with plaque psoriasis in the fourth quarter (Also see "Psoriasis Market Snapshot: An Area Drug Makers Are Itching To Get Into" - Pink Sheet, 23 Jul, 2012.).
Lilly’s portfolio of autoimmune disease therapies also includes baricitinib (INCB28050), an oral Janus kinase 1/2 inhibitor for rheumatoid arthritis, psoriasis and diabetic neuropathy, that Lilly licensed from Incyte Corp. in 2009 [See Deal].
Lilly recently began a Phase III program for the drug in moderate to severe rheumatoid arthritis, with RA-BEGIN, comparing baricitinib to methotrexate in treatment-naïve patients with limited or no exposure to methotrexate, and RA-BEAM, in patients with inadequate response to methotrexate, currently recruiting. RA-BEACON, in patients with an inadequate response to treatment with a tumor necrosis factor inhibitor despite ongoing treatment with conventional disease-modifying antirheumatic drugs (DMARDs), and RA-BUILD, in patients who had an inadequate response or intolerance to at least one conventional DMARD and have not tried a biologic DMARD, are listed in clinicaltrials.gov but not yet recruiting patients.
Movement On The Solanezumab Front
Lilly was in the news the day before as well. On Dec. 12, the firm announced that it would conduct an additional Phase III study of its Alzheimer’s disease therapy solanezumab, this time in patients with mild disease, following discussions with regulators concerning the drug’s regulatory future.
Lilly announced in October that though the drug had essentially failed, a pooled analysis of two Phase III trials showed that patients with mild disease had a statistically significant 34% decrease in their rate of cognitive decline. At the time, the company hinted that it was contemplating an FDA submission based on that finding but said that it would first consult with regulators (Also see "Efficacy Signal For Lilly’s Solanezumab Stirs The Alzheimer’s Pot" - Pink Sheet, 15 Oct, 2012.).