Biotech Values

[poorgradstudent]

INCY:

The abstracts for RA-BEGIN and RA-BEAM from ACR 2015. Pleasantly surprised by baricitinib competing much better with adalimumab than I would have expected, although the AE profile merits attention. If you follow the links, there are tables with the efficacy and AE data.

RA-BEAM :

Baricitinib Versus Placebo or Adalimumab in Patients with Active Rheumatoid Arthritis (RA) and an Inadequate Response to Background Methotrexate Therapy: Results of a Phase 3 Study

Background/Purpose: In phase 3 studies, baricitinib (bari) improved disease activity in patients (pts) with active RA and an inadequate response (IR) to conventional synthetic DMARDs1 or biologic DMARDs2. This abstract reports the 24-wk results from a 52-wk, global, phase 3, double-blind, placebo (PBO) and active-controlled study of bari in MTX-IR RA pts.

Methods: Pts with active RA (TJC≥6 & SJC≥6 & hsCRP≥6 mg/L) despite stable background MTX were randomized 3:3:2 to PBO, bari 4 mg once daily (QD), or adalimumab (ADA) 40 mg biweekly (Q2W), stratified by region and baseline joint erosion status. Non-responders were rescued from Wk 16. At Wk 24, pts on PBO switched to bari 4 mg QD. The primary endpoint was ACR20 response at Wk 12 for bari vs. PBO. Major secondary endpoints included comparisons of bari vs. ADA for ACR20 and change in DAS28-CRP at Wk 12.

Results: Of 1305 randomized pts, 89%, 94% and 93% completed Wk 24 in PBO, bari and ADA groups, respectively. Rescue rates were 26%, 7% and 12% for PBO, bari and ADA, respectively. ACR20 response at Wk 12 was higher for bari vs. PBO (70% vs. 40%, p≤.001 – Table 1). At Wks 12 and 24, statistically significant improvements in ACR 20/50/70 & HAQ-DI response rates, and DAS28, CDAI, and SDAI low disease activity and remission rates were seen for bari vs. PBO, many as early as Wk 1. Compared to ADA, bari was superior with respect to measures including ACR20 response and improvement in DAS28-CRP at Wk 12. Compared to PBO, daily diary measures of morning joint stiffness (MJS) duration and severity, worst tiredness, and worst joint pain were significantly improved in pts receiving bari, from as early as Wk 1. Rates of treatment-emergent adverse events (TEAEs), including infections, were higher for bari and ADA compared to PBO (Table 2). Compared to PBO, serious adverse events (SAE) rates were similar for bari and lower for ADA; serious infection rates were similar across groups. Two deaths occurred (bari), 1 pneumonia and 1 duodenal ulcer haemorrhage. Five malignancies were reported, 2 bari and 3 PBO. Three potential opportunistic infections occurred, 2 bari and 1 PBO; none were SAEs. One case of tuberculosis occurred (ADA). There were no GI perforations. Lab abnormalities were consistent with other phase 3 studies1,2; few led to discontinuation.

Conclusion: In pts with active RA despite background MTX, once-daily oral bari was associated with significant clinical improvements compared to PBO and to ADA, with an acceptable safety and tolerability profile.


RA-BEGIN:

Background/Purpose:

In 2 completed phase 3 studies, baricitinib (bari) improved disease activity with a satisfactory safety profile in patients (pts) with moderately-to-severely active RA who were inadequate responders to either conventional synthetic1 or biologic2DMARDs. This abstract reports results from a phase 3 study of bari administered as monotherapy or in combination with methotrexate (MTX) to pts with early active RA who had limited or no prior treatment with DMARDs. MTX monotherapy was the active comparator.

Methods: Pts with active RA (TJC & SJC ≥6, hsCRP ≥3.6 mg/L) and no previous DMARD treatment other than ≤3 doses of MTX were randomized 4:3:4 to MTX, bari 4 mg once daily (QD; bari monotherapy), or bari 4 mg QD + MTX for up to 52 wks. MTX dose, with or without bari, was up-titrated from 10 to 20 mg once weekly over 8 weeks (wks). Rescue was not allowed prior to Wk 24, the time point for primary and all major secondary efficacy endpoints. The primary objective evaluated non-inferiority of bari 4 mg monotherapy to MTX on ACR20 at Wk 24 (using a 12% margin).

Results: Of 584 randomized pts, 87%, 91%, and 89% of pts completed Wk 24 in the MTX, bari 4 mg monotherapy, and bari 4 mg + MTX groups, respectively. ACR20 response at Wk 24 was higher with bari 4 mg monotherapy vs. MTX (77% vs. 62%, p≤.01). Compared to MTX, bari 4 mg monotherapy produced significantly greater improvements in multiple secondary measures of disease activity (Table 1), many as early as Wk 1. MTX in combination with bari 4 mg did not appear to increase the benefit observed with bari 4 mg monotherapy. Clinical remission was seen in a significantly higher proportions of pts treated with bari 4 mg alone or in combination with MTX compared to MTX alone (Table 1). Rates of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were similar across groups (Table 2). Through 24 wks, 2 (1.0%), 6 (3.8%) and 14 (6.5%) pts discontinued the study because of an adverse event in the MTX, bari 4 mg monotherapy, and bari 4 mg + MTX groups, respectively. No GI perforations occurred during the study. Laboratory abnormalities were generally less frequent in the bari 4 mg group compared to either the MTX or bari 4 mg + MTX groups (Table 2).

Conclusion:

In pts with early RA, all treatment groups experienced improvements in disease activity with bari 4 mg monotherapy producing significantly larger and more rapid improvements and higher rates of clinical remission compared to MTX monotherapy, with a satisfactory safety profile. MTX addition to bari 4 mg did not increase the benefit observed with bari monotherapy, while it appeared to increase the frequency of laboratory abnormalities.