Fourth Phase 3 study reports out for Lilly/Incyte's JAK1/2 inhibitor, baricitinib - RA-BEAM demonstrates superiority over Humira in biologic naive rheumatoid arthritis

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• Lilly has been reading out on its Phase 3 baricitinib program over the past year in preparation for filing expected towards the end of 2015
  
• RA-BEACON (bDMARD-IR) and RA-BUILD (cDMARD-IR) were reported in Q4 2014 and Q1 2015.  More recently, RA-BEGIN demonstrated non-inferiority of baricitinib vs MTX both as monotherapy, mostly in DMARD naïve patients (conventional and biologic)
• A fourth study, RA-BEAM (H2H vs Humira) has now read out.  This study compared baricitinib to placebo or Humira in biologic naive patients
  
• The study met its primary endpoint with ACR20 at 12wk superior to that of placebo.  Radiographic progression at 24wks was also reduced
• Superiority was also demonstrated over Humira (secondary endpoints) on ACR20 and DAS28-hsCRP measures at 24wks.  Superiority was reportedly maintained through 52wk
• Lilly's press release comments that "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".  This refers to the QD dosing regimen for baricitinib vs BID dosing for Xeljanz.  Of note, a modified release QD formulation of the later is currently under regulatory review
• Limited safety data was reported - one case of TB infection was reported each with baricitinib and Humira.  Infection rates were higher for baricitinib and Humira vs placebo although differences between the active groups were not reported
• Lilly suggests RA-BEGIN but not RA-BEAM will be reported at ACR in November
  

Comments:  The topline efficacy reported for RA-BEGIN (DMARD naive) a few weeks ago was important securing a possible first line systemic approach for baricitinib.  Although the degree of efficacy has yet to be reported we expect it to be considerable given that efficacy in RA-BUILD (cDMARD experienced) was impressive and paralleled that reported in similar studies of Xeljanz.  Given the likely cost of baricitinib and limited safety data expected at launch, RA-BUILD is possibly more important than RA-BEGIN, establishing baricitinib as a pre-biologic option between cDMARD and bDMARD.  In exception RA-BEGIN may support early use in patients unwilling or unable to receive MTX.  Today's RA-BEAM data reinforces RA-BUILD, not only supporting pre-biologic use but suggesting baricitinib use instead of Humira after the failure of a cDMARD.  This now given the rheumatologist further interesting  decisions - not only is there a choice between IL-6 blockade through (Ro)Actemra or TNFi, there is also the choice between a JAKi and a biologic.  Data are available to guide most decision points in this increasingly complex treatment paradigm, which is good for the patient.  Further data would however be useful to help guide the future decision between post-cDMARD baricitinib and (Ro)actemra or Enbrel.  In reality with Xeljanz already available as a JAKi, we would expect baricitinib to be reserved at first as a post-biologic option supported by RA-BEACON unless RA-BEAM reveals extraordinarily impressive benefits over Humira

Tofacitinib demonstrates efficacy in Phase 3 ulcerative colitis induction trials

Source:  UpdatesPlus-IBD

• Pfizer has announced topline results from two identical OCTAVE induction studies
• Both studies met their primary endpoints (remission at 8wks) The two studies evaluated oral tofacitinib (10mg BID) in 1139 patients with moderate/severe ulcerative colitis
• Patients must have been previously been intolerant or unresponsive to corticosteroids, azathioprine/6 MP), or a TNFi
  
• Pfizer's press release comments that that are no new AEs
  
• A third study, OCTAVE Sustain investigating maintenance treatment with tofacitinib is anticipated by the end of 2016

Comments:  Obviously further data are required before tofacitinib can be more fully evaluated as an option in ulcerative colitis patients.  Safety is one issue, particularly as a 10mg dose was employed rather than the 5mg dose of tofacitinib approved as Xeljanz in the US for rheumatoid arthritis.  The absence of new AEs is promising, however it will be important to know the rate of known AEs.  This is not only important for ulcerative colitis; safety data may be important for use in psoriasis as well, since treatment with 10mg tofacitinib is required to produce non-inferior efficacy to that of Enbrel in the psoriasis study, OPT Compare.  The degree of efficacy in ulcerative colitis remains to be seen and particularly whether prior treatment history affects tofacitininb response.  It is unclear if OCTAVE will be presented at UEGW in October, from where we will be reporting.  The late breaker deadline was August 25. [Contact us if you are interested in our conference reporting service]