June 2, 2014 – Novartis today presented results from a pivotal Phase III trial showing a 37% improvement in progression-free survival (PFS) when using the investigational compound LBH589 (panobinostat) in combination with bortezomib and dexamethasone compared to treatment with the same regimen with placebo in patients with relapsed or relapsed and refractory multiple myeloma, meeting the primary endpoint of the study (hazard ratio=0.63 [95% confidence interval (CI): 0.52 to 0.76]; p<0.0001)[1] (Press release Novartis, JUN 2, 2014, View Source [SID:1234500933]). The PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) trial results were presented in an oral session at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago.
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"Almost all patients with multiple myeloma ultimately relapse and become resistant to treatment, so new therapies are critical for continuing to manage the disease and improve outcomes," said study investigator Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "These are the first Phase III results to show meaningful clinical benefit and provide scientific support for adding LBH589 to bortezomib-based treatment for patients with relapsed or relapsed and refractory multiple myeloma and provide a strong rationale for the use of histone deacetylase inhibitors as part of the therapeutic armamentarium in this setting."
In the LBH589 arm, there was a 4-month prolongation of median PFS (12 months versus 8 months in the placebo arm). The effect of LBH589 was observed across all patient subgroups (for example by age or prior exposure to bortezomib or immunomodulatory therapy)[1]. The findings also showed that adding LBH589, a pan-deacetylase (pan-DAC) inhibitor, to bortezomib and dexamethasone led to a significant increase in higher quality responses compared to standard-of-care therapy alone, as evidenced by a nearly two-fold increase in complete/near complete response rates (28% versus 16%, respectively; p=0.00006)[1].
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) and diarrhea (26% versus 8% with placebo). Adverse events were generally manageable through supportive care and dose reductions[1].
Multiple myeloma, a cancer of white blood cells predominantly affecting the bone marrow, impacts approximately 1 to 5 in every 100,000 people worldwide each year[2]. With a five-year survival rate of 44%, there is an unmet treatment need for people living with this cancer[3]. As a pan-DAC inhibitor, LBH589 potentially provides a novel mechanism of action to treat multiple myeloma and works by blocking a key class of cancer cell enzymes, which ultimately leads to cellular stress and death of these cells[4].
In May, LBH589 was granted priority review by the US Food and Drug Administration (FDA) and additional global regulatory submissions are underway. FDA priority review status is given to therapies that offer major advances in treatment[5].
"LBH589 is a strong example of how our research and development strategy of targeting key pathways in novel ways can benefit patients," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "PANORAMA-1 data show that adding LBH589 to the standard-of-care treatment for patients with relapsed or relapsed and refractory multiple myeloma offers an innovative and effective treatment option to address an unmet need."
Additional data from PANORAMA-1 will be presented at upcoming medical congresses this year, including an oral presentation at the 19th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) on June 14 in Milan, Italy.