Novartis announced that the US Food and Drug Administration's (US FDA) Oncologic Drugs Advisory Committee (ODAC) did not recommend the investigational compound LBH589 (panobinostat), a pan-deacetylase (pan-DAC) inhibitor, for patients with previously treated multiple myeloma when used in combination with bortezomib and dexamethasone.
The Committee's vote will be considered by the FDA in its review of the LBH589 new drug application (NDA), but the FDA is not bound to follow the Committee's guidance. The final decision regarding US approval is made by the FDA.
"We are disappointed by this voting outcome and believe the results from our clinical trials provide strong evidence to support LBH589 as a potential first-in-class treatment option for multiple myeloma, a cancer where an unmet patient need exists," said Bruno Strigini, president, Novartis Oncology. "We will continue to work with the FDA as it completes its review of the US application."
Data presented at meeting included two clinical studies evaluating LBH589 in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma: a phase III randomised, double-blind, placebo-controlled, multicentre global registration trial called PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) and a phase II US multicentre, single-arm, open-label study called PANORAMA-2.
Multiple myeloma is a cancer of the plasma cells, a kind of white blood cell present in bone marrow-the soft, blood-producing tissue that fills the center of most bones. The cancer is caused by the production and growth of abnormal cells within the plasma, which multiply and build up in the bone marrow, pushing out healthy cells and preventing them from functioning normally. Multiple myeloma is an incurable disease with a high rate of relapse (when the cancer returns) and patients often become refractory (unresponsive to therapy), despite currently available treatments. It typically occurs in individuals 60 years of age or older, with few cases in individuals younger than 40.
Epigenetics is the cell programming that governs gene expression and cell development. In multiple myeloma, the normal epigenetic process is disrupted (also called epigenetic dysregulation) resulting in the growth of cancerous plasma cells, potential resistance to current treatment and ultimately disease progression.
LBH589 is a potent pan-deacetylase (pan-DAC) inhibitor that if approved will be a first-in-class therapy for patients with previously treated multiple myeloma. As an epigenetic regulator, LBH589 may help restore cell programming in multiple myeloma.
Because LBH589 is an investigational compound, the safety and efficacy profile has not yet been established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that LBH589 will ever be commercially available anywhere in the world.