abbvie inc (4AB) Snapshot

AbbVie Inc. announced preliminary results from a Phase I study of ABT-199/GDC-0199, an investigational BCL-2 (B-cell lymphoma 2) selective inhibitor, in patients with high-risk relapsed/refractory chronic lymphocytic leukemia (CLL), and in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). High-risk CLL patients are those with deletions of chromosome 17p or whose disease is refractory to fludarabine therapy. This Phase I, open-label, multicenter, international trial was designed to assess the safety, determine the maximum tolerated dose and recommended Phase II dose, and evaluate the pharmacokinetics of ABT-199/GDC-0199 in patients with relapsed/refractory CLL and NHL. Secondary objectives included preliminary efficacy, including objective response rate, duration of response, time to progression, progression-free survival and overall survival. As of April 2013, 56 patients have enrolled in the CLL arm of the Phase I trial, and 40 patients are currently active. Study participants were given a single oral dose of ABT-199/GDC-0199, followed by six days without medication, before continuous once-daily dosing. Due to concerns over tumor lysis syndrome (TLS), the initial dose was reduced and daily dosing was modified. Single-agent activity was observed in the trial and warrants further single-agent and combination trials evaluating ABT-199/GDC-0199 in patients with CLL. Dose and schedule evaluation will continue. Of the 56 patients enrolled, 34 were considered high-risk CLL patients -- those with deletions of chromosome 17p or whose disease is refractory to fludarabine therapy. In the post-hoc analysis to determine if high-risk CLL patients could have similar response rates to the overall study population, 17 (30%) patients had 17p deletion and 18 (32%) had fludarabine-refractory CLL. During the study, 16 patients discontinued treatment; nine due to progressed disease and seven for other reasons (two due to TLS, three for other illnesses, one for thromboembolic event and one consent withdrawal). The most common hematological adverse events (AEs) during the study were neutropenia (39%), thrombocytopenia (18%) and anemia (13%). The most common non-hematological AEs were diarrhea (41%), nausea (38%), fatigue (29%), upper respiratory tract infection (27%) and cough (23%). In the first study group, TLS occurred in all three of the enrolled patients; once the modified dosing schedule was utilized, three of the 53 patients experienced TLS, one of which was a fatal AE that occurred within dose escalation to 1200mg.

Bristol-Myers Squibb Company and AbbVie Inc. announced updated efficacy and safety data from a small, randomized Phase 2, open-label study in patients with previously-treated multiple myeloma that evaluated two doses of the investigational monoclonal antibody elotuzumab (10 mg/kg and 20 mg/kg) in combination with lenalidomide and low-dose dexamethasone. In the 10 mg/kg arm (N=36), which is the dose used in the ongoing Phase 3 trials, median progression-free survival (PFS), or the time without disease progression, was 33 months after a median follow-up of 20.8 months (95% CI: 14.9-NA) and the objective response rate (ORR) was 92%. As previously reported, median PFS was 18 months in the 20 mg/kg arm (N=37) after a median follow-up of 17.1 months (95% CI: 12.912-32.361) and ORR was 76%. The safety data were consistent with previously-reported results for elotuzumab from this trial. In patients receiving elotuzumab 10 mg/kg or 20 mg/kg, most treatment-emergent adverse events occurred within 18 months of initiating therapy. The most common Grade 3/4 adverse events (seen in > 5% of patients) for the 10 mg/kg and 20 mg/kg arms respectively were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5 %), fatigue (8% and 9%), and hypokalemia (8% and 5%). As previously reported at the 2012 American Society of Hematology annual meeting, two deaths occurred on study (multiple adverse events [n=1; pneumonia, multiple organ failure and sepsis]). These data were presented on June 15, 2013 at the 18(th) Annual Congress of the European Hematology Association (EHA) in Stockholm, Sweden.

AbbVie Inc. announced the results from the CONCERTO trial, the first randomized, controlled trial assessing different predefined doses of methotrexate (MTX) in combination with HUMIRA (adalimumab) for the treatment of moderate to severe rheumatoid arthritis (RA). CONCERTO shows that at week 26 of treatment, a statistically significant increasing trend was observed in the proportion of patients achieving low disease activity with an increasing dose of MTX when used with open-label HUMIRA. Results were presented at the European League against Rheumatism (EULAR) 2013 Congress in Madrid, Spain. The primary objective of CONCERTO was to determine a dose-response pattern of MTX in combination with HUMIRA in MTX and biologic-naive patients with active moderate to severe RA for less than 1 year. Patients were randomized into four treatment arms, receiving 40 mg of open-label HUMIRA every other week in combination with weekly oral MTX at 2.5 mg, 5 mg, 10 mg or 20 mg. For all four treatment groups, the primary endpoint was the achievement, at week 26, of low disease activity, defined by a Disease Activity Score 28 (DAS28) of <3.2% ages of patients achieving low disease activity were as follows: 43% (n=98) of patients in the 2.5 mg per week MTX group; 44 % (n=100) of patients in the 5 mg per week MTX group; 57% (n=99) of patients in the 10 mg per week MTX group; and 60% (n=98) of patients in the 20 mg per week MTX group (P<0.005 for the trend). DAS28 measurement is a composite index that includes variables such as tender and swollen joint counts, a patient's visual analog scale for disease activity and C-reactive protein (CRP) as a measure of inflammation. CONCERTO was double-blind for the MTX dose and open-label for the use of HUMIRA. The clinical response rates in this trial were similar to the results from a previous HUMIRA study in patients with early moderate to severe RA (the PREMIER trial). Safety was assessed in terms of adverse events (AEs) for all patients who received at least one dose of study drug. AEs were consistent with the known profile of HUMIRA and were generally consistent between arms, occurring most frequently in the HUMIRA plus MTX 20 mg arm.