Eli Lilly and Incyte said Wednesday that a fourth Phase III trial of baricitinib in patients with moderately-to-severely active rheumatoid arthritis (RA) met its primary endpoint, demonstrating superiority versus placebo after 12 weeks of treatment based on ACR20 response. The selective inhibitor of JAK1 and JAK2 was also superior to AbbVie's Humira (adalimumab) on key secondary objectives of ACR20 response and improvement in the DAS28-hsCRP disease activity score after 12 weeks of treatment.
"RA-BEAM is the first study to demonstrate that a once-daily oral treatment was superior in improving signs and symptoms of rheumatoid arthritis compared to the current injectable standard of care," commented David Ricks, president of Lilly Bio-Medicines. The trial, which enrolled more than 1300 patients with active RA despite treatment with methotrexate, evaluated the safety and efficacy of baricitinib against placebo for 24 weeks or Humira for 52 weeks. Participants on background methotrexate were randomised to one of three treatment arms, receiving either once-daily oral baricitinib, Humira administered by injection every-other-week or placebo.
In addition to meeting the primary and key secondary endpoints, top-line results showed that baricitinib was superior to placebo in preventing progressive radiographic structural joint damage after treatment that lasted 24 weeks. The drugmakers pointed out that the benefits of baricitinib observed at 12 weeks and 24 weeks were maintained through 52 weeks of therapy.
With regard to safety, the companies said rates of serious adverse events were similar between baricitinib and placebo, but lower for Humira, while serious infection rates were comparable across the groups. Further, the incidence of treatment-emergent side effects, including infections, was higher for baricitinib and Humira than it was for placebo, while discontinuations due to adverse events occurred with similar frequency across treatment groups.
Commenting on the results, Nomura analyst Ian Somaiya remarked that "taken together, we believe these data should support a superiority label claim in both the US and EU," which he said could support peak sales estimates of about $2 billion. Meanwhile, Evercore ISI analyst Mark Schoenebaum stated "these efficacy results were consistent with data from Pfizer's JAK inhibitor Xeljanz (tofacitinib) at the high (unapproved) dose of 10 mg twice daily and thus largely expected." However, he noted the lower rate of serious adverse events for Humira, saying "although interested in the detailed efficacy data, we are particularly interested in the detailed safety data from the trial and also long-term safety, which we believe would be a major driver of uptake for chronic therapy in RA."
Last December, Eli Lilly and Incyte released top-line results from the Phase III RA-BEACON study, demonstrating that baricitinib was associated with improved ACR20 responses over placebo after 12 weeks in patients with moderately-to-severely active RA who had failed one or more tumour necrosis factor inhibitors and who were taking stable doses of conventional disease-modifying anti-rheumatic drug (DMARD) therapy. Earlier this year, data from the late-stage RA-BUILD study, which enrolled patients with moderately-to-severely active RA who had either failed or could not tolerate treatment with at least one conventional DMARD, showed the drug met the primary endpoint of significantly improving ACR20 response versus placebo after 12 weeks of treatment.
Recently, Eli Lilly and Incyte announced that baricitinib also hit the main goal of the Phase III RA-BEGIN trial, which will be presented at the annual meeting of the American College of Rheumatology (ACR) next month. The companies added they plan to submit results from RA-BEAM and the other late-stage trials in the baricitinib clinical development programme for presentation at scientific meetings and publication in peer-reviewed journals this year and in 2016.
For additional analysis, see ViewPoints: Baricitinib could be Eli Lilly's near-term bounce back play.
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