Positive Results Announced in Phase 3 Multiple Myeloma Trial of Panobinostat

Novartis announces a demonstrated improvement in progression-free survival in patients using LBH589 (panobinostat) with bortezomib and dexamethasone.

In a news release published on December 6, 2013, Novartis Pharmaceuticals announced positive results of a late-stage clinical trial with LBH589 (panobinostat) in the treatment of patients with multiple myeloma. In the phase 3 clinical trial dubbed PANORAMA (PANobinostat ORAl in Multiple MyelomA), investigators measured progression-free survival and overall survival in 769 patients with relapsed or relapsed and refractory multiple myeloma receiving bortezomib and dexamethasone with either LBH589 or placebo.

Compared with bortezomib and dexamethasone alone, addition of LBH589 significantly extended progression-free survival in patients with relapsed or refractory multiple myeloma. If approved, Novartis expects LBH589, a pan-deacetylase inhibitor of class I, II, and IV histone and non-histone deacetylase enzymes, to become a first-in-class treatment.

The full results of the phase 3 trial are not expected until March 2014, despite the release of positive early results on December 6.

Panobinostat works synergistically with bortezomib to target 2 enzyme systems associated with multiple myeloma including the proteasome and the aggresome. Due to its synergistic action with bortezomib, investigators tested efficacy of panobinostat in patients who had used bortezomib in the past.

Results of an earlier phase 2 trial with 55 patients who had received a median of 4 prior regimens and a median of 2 prior bortezomib-containing regimens revealed a 34.5% overall response rate comprising 1 complete response and 18 partial responses. Grade 3 and 4 adverse reactions included thrombocytopenia, diarrhea, fatigue, anemia, neutropenia, and pneumonia. One patient experienced grade 3 peripheral neuropathy.

For later-line treatment of multiple myeloma in patients who have failed on bortezomib, early results indicate that adding panobinostat may help restore response to treatment through a synergistic mechanism.