Novartis presents positive Phase III results of Farydak therapy at EHA

Jun 16 2015

Novartis today presented results from a pivotal Phase III clinical trial exploratory subgroup analysis showing a 7.8-month improvement in median progression-free survival (PFS) when using Farydak^® (panobinostat, previously known as LBH589) in combination with bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma who had received two or more prior regimens, including bortezomib and an immunomodulatory agent (IMiD). Findings are being presented in an oral session at the 20^th Congress of the European Hematology Association (EHA) in Vienna.

“I am encouraged by these results because they show that therapy with Farydak, in combination with bortezomib and dexamethasone, translates into a meaningful prolongation in progression-free survival (by 7.8 months) for multiple myeloma patients previously treated with IMiDs and bortezomib who received 2 or more prior regimens,” said study investigator Jesús San Miguel, MD, Director of Clinical and Translational Medicine, Clínica Universidad de Navarra, Pamplona, Spain. “These data also provide physicians with a better understanding of the clinical use of Farydak, a histone deacetylase inhibitor, a promising new drug class for this difficult-to-treat patient population with a high unmet need.”

These data are from a subgroup analysis of 147 patients with relapsed or relapsed and refractory multiple myeloma who had received two or more prior regimens, including bortezomib and an IMiD, in the Phase III, randomized, double-blind, placebo-controlled, multicenter global registration trial called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA). This subgroup excluded patients who received only one prior regimen. The analysis showed that in this subgroup, median PFS increased to 12.5 months in the panobinostat-treatment arm compared to 4.7 months in the placebo plus bortezomib and dexamethasone arm (hazard ratio=0.47 [95% confidence interval (CI), 0.31-0.72]). Treatment with panobinostat in combination with bortezomib and dexamethasone when compared to the placebo arm also led to an increase in complete/near complete response rates (21.9% versus 8.1%) and overall response rate (58.9% versus 39.2%).

Common grade 3/4 non-hematologic adverse events (AEs) in the panobinostat-treatment arm compared to the placebo arm for this subgroup included diarrhea (33.3% versus 15.1%), asthenia/fatigue (26.4% versus 13.7%) and peripheral neuropathy (16.7% versus 6.8%). The most common grade 3/4 hematologic laboratory abnormalities in the panobinostat-treatment arm compared to the placebo arm were thrombocytopenia (68.1% versus 44.4%), lymphopenia (48.6% versus 49.3%) and neutropenia (40.3% versus 16.4%). The percentage of on-treatment deaths in the panobinostat-treatment arm compared to the placebo arm in this subgroup was similar (6.9% versus 6.8%).

“These findings, which follow the recent FDA approval of Farydak, provide clinicians with additional evidence on the value of this new treatment to help optimize the management of multiple myeloma," said Bruno Strigini, President, Novartis Oncology. “Multiple myeloma is often complicated because patients who stop responding or become resistant to therapies have limited treatment options. Therefore, these patients may benefit from therapies like Farydak.”

Panobinostat, in combination with bortezomib and dexamethasone, was approved as Farydak by the US Food and Drug Administration (FDA) in February 2015 for the treatment of patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an IMiD. This indication is approved under accelerated approval based on PFS reported in a separate analysis of 193 patients in the PANORAMA-1 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The FDA has approved a risk evaluation and mitigation strategy (REMS) for Farydak. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Farydak treatment. Farydak is the first histone deacetylase (HDAC) inhibitor available to patients with multiple myeloma. As an HDAC inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.