GSK previewed the data at AASLD in the fall, and the disclosure of an imbalance in thromboembolic events and deaths sent LGND shares cratering to as low as ~10.50. LGND recovered to ask high as nearly 19 before settling back recently. The full abstract release today doesn't seem to be causing an undue LGND sell-off (down 4.6% on higher than average volume) on a bad market day for most biotechs.
See below for the full abstract.
RESULTS OF ENABLE 2, A PHASE 3, MULTICENTER STUDY OF ELTROMBOPAG AND PEGINTERFERON ALFA-2B TREATMENT IN PATIENTS WITH HEPATITIS C AND THROMBOCYTOPENIA
G. Dusheiko1*, N. Afdhal2, E.G. Giannini3, P.J. Chen4, K.-H. Han5, M. Rodriguez-Torres6, S. Rugina7, E. Lawitz8, A. Streinu-Cercel9, M.L. Shiffman10, F. Poordad11, Y. Mostafa Kamel12, A. Brainsky13, J. Geib13, S.Y. Vasey13, R. Patwardhan13, F. Campbell12, D. Theodore14
1Royal Free Hospital, London, UK, 2Harvard Medical School, Boston, MA, USA, 3University of Genoa, Genoa, Italy, 4National Taiwan Hospital, Taipei, Taiwan R.O.C., 5Severance Hospital, Seoul, Republic of Korea, 6Fundacion de Investigacion de Diego, San Juan, Puerto Rico, 7Municipal Hospital Constanta, Constanta, Romania, 8Digestive Disease Centers, San Antonio, TX, USA, 9National Institute of Infectious Diseases 'Prof. Dr. Matei Bals', Bucharest, Romania, 10Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, 11Cedars-Sinai Medical Center, Los Angeles, CA, USA, 12GlaxoSmithKline, Uxbridge, UK, 13GlaxoSmithKline, Collegeville, PA, 14GlaxoSmithKline, Research Triangle Park, NC, USA. *firstname.lastname@example.org
Background and aims: Thrombocytopenia limits the ability to initiate and maintain peginterferon alfa-2b [PEG-2b]+ribavirin therapy in patients with cirrhosis due to hepatitis C (HCV). PEG-2b is not recommended for patients with platelets < 100Gi /L. Eltrombopag is an oral thrombopoietin receptor agonist that improved sustained virologic response (SVR) in ENABLE 1 (PEG-2a/ribavirin). ENABLE 2 was a second study to evaluate the ability of eltrombopag to increase platelet counts, providing patients with pre-existing thrombocytopenia the opportunity to initiate PEG-2b and achieve SVR.
Methods: In Part 1, patients with HCV and platelets < 75Gi/L received eltrombopag 25mg, increased to 50, 75, or 100mg daily until platelets reached ≥100Gi/L to enter Part 2. In Part 2, patients eligible for PEG-2b (1.5µg/kg/week) and ribavirin (weight-based dosing) were randomized 2:1 to eltrombopag or placebo. Treatment was administered for 24 weeks or 48 weeks according to genotype. The primary endpoint was SVR.
Results: 805 patients were enrolled, 80% with bridging fibrosis or cirrhosis (FibroSURE™). Median platelets were 59Gi/L at enrollment and 93Gi/L by week 2 of eltrombopag treatment. 759 patients (94%) initiated HCV therapy (eltrombopag, 506; placebo, 253). In Part 2, median platelet counts in the eltrombopag and placebo arms were 136Gi/L vs 140Gi/L at randomization but 105Gi/L vs 51Gi/L at week 4, and > 50Gi/L throughout for 81% vs 23% of patients. Compared with placebo, eltrombopag was associated with improved SVR (19% vs 13%, p=0.0202), fewer antiviral dose reductions (54% vs 73%, p=0.0001), improved early virological response (EVR; 62% vs 41%, p< 0.0001), and end-of-treatment response (38% vs 23%, p< 0.0001). Adverse event (AE) rates were (eltrombopag, placebo): any AE (94%, 93%); serious AE (20%, 15%); events suggestive of decompensation (15%, 8%); thromboembolic events (4%, < 1%), and death (4%, 2%).
Conclusions: Eltrombopag increased and maintained platelet counts throughout PEG-2b/ribavirin treatment in patients who would otherwise be ineligible for antiviral therapy. Eltrombopag treatment was associated with clinically meaningful improvement in SVR, as previously reported with PEG-2a/ribavirin treatment in ENABLE 1. Unlike previously reported in ENABLE 1, there was an increased incidence of thromboembolic complications with eltrombopag treatment, which requires further analysis.
Prof. Geoffrey M. Dusheiko, University College London School of Medicine and Royal Free Hospital , Hepatology / Viral Hepatitis , London , UK
Assigned in sessions:
20.04.2012, 16:00-18:00, Parallel Session, PS06, Parallel Session: Viral Hepatitis - Clinical, Hall A