Novartis reports data from Phase III PANORAMA-1 trial of LBH589 in patients with multiple myeloma

In the Phase III PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) trial, the addition of LBH589 also led to clinically meaningful increases in complete and near complete response rates and duration of response. The effect of LBH589 was observed across all patient subgroups].

Multiple myeloma is a cancer of white blood cells that predominantly affects the bone marrow, impacting approximately 1 to 5 in every 100,000 people worldwide each year, and is increasing in prevelance. Most people with multiple myeloma ultimately relapse and become resistant to treatment, so new therapies with novel mechanisms of action are critical for continuing to manage the disease and improve outcomes. If approved, LBH589, a pan-deacetylase (pan-DAC) inhibitor, will be first in its class of anticancer agents available to this population.

"The PANORAMA-1 study is the first Phase III trial to show the superiority of LBH589 plus bortezomib and dexamethasone over one of the standard two-drug regimens for patients with relapsing and/or refractory multiple myeloma," said lead study investigator Jesus San-Miguel, MD, Director of Clinical and Translational Medicine, Clínica Universidad de Navarra, Pamplona, Spain. "These results show that by adding a new mechanism of action, pan-DAC inhibition, there is a significant benefit for this patient population."

Side effects were consistent with those previously seen in LBH589 studies. The most common Grade 3/4 adverse events in the LBH589 combination arm were thrombocytopenia (67% versus 31% with placebo), lymphopenia (53% versus 40% with placebo), neutropenia (35% versus 11% with placebo), diarrhea (26% versus 8% with placebo) and neuropathy (18% versus 15% with placebo). Adverse events were generally manageable through supportive care and dose reductions.

"The majority of people living with multiple myeloma eventually will stop responding to treatment or relapse, which underscores the need for new treatment options," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "The PANORAMA-1 results provide strong evidence of the potential impact LBH589 could have for the multiple myeloma community. We are committed to working with regulatory authorities to make this treatment available to patients as soon as possible."

Based on the PANORAMA-1 data, in May, LBH589 was granted priority review by the US Food and Drug Administration (FDA) and a regulatory application was submitted to the European Medicines Agency (EMA). Additional global regulatory submissions are underway. FDA priority review status is given to therapies that may offer major advances in treatment.

The PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) clinical trial is a Phase III randomized, double-blind, placebo-controlled, multicenter global registration trial to evaluate LBH589 in combination with bortezomib and dexamethasone against bortezomib and dexamethasone alone in patients with relapsed or relapsed and refractory multiple myeloma who failed on at least one prior treatment. The study of 768 patients took place in 215 clinical trial sites worldwide. The primary endpoint of the trial was progression-free survival (PFS). Data for overall survival, the key secondary endpoint of the trial, are not yet mature. Other secondary endpoints include overall response rate, duration of response and safety.

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 resistance (when the therapy stops working), 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-DAC inhibitor that if approved will be a first-in-class treatment for patients with relapsed or relapsed and refractory 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.