- Results show adding LBH589 to bortezomib and dexamethasone significantly improved PFS by 37%, meeting Phase III study primary endpoint
- Median PFS increased by 4 months (12 months in LBH589 arm versus 8 months in placebo arm); effect of LBH589 observed across all patient subgroups
- Most people with multiple myeloma will relapse or become refractory; if approved, LBH589 will be first in its class of anticancer agents available to this population
- Based on these data, US FDA granted priority review in May; additional global regulatory filings are underway
Basel, 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). 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) in Chicago.
"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). 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).
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.
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. With a five-year survival rate of 44%, there is an unmet treatment need for people living with this cancer. 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.
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.
"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) on June 14 in Milan, Italy.
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.
LBH589 is a potent oral pan-inhibitor of class I, II, and IV histone (and non-histone) deacetylase enzymes (HDACs/DACs). It works by blocking a key class of cancer cell enzymes, which ultimately leads to cellular stress and death of these cells.
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.
About Multiple Myeloma
Multiple myeloma is a cancer of plasma cells, a type of white blood cell in the bone marrow that produces antibodies and helps fight infection. When the plasma cells become cancerous and multiply, they are known as myeloma cells. The buildup of myeloma cells causes an abnormal plasma cell level in the blood, overwhelming the production of healthy cells.
Multiple myeloma typically occurs in individuals 50 years of age and older, with few cases in individuals younger than 40. Common symptoms include a high level of calcium in the blood, decreased red blood cells, kidney failure, bone damage and pain and fatigue, but may vary from person to person. There are currently no curative therapies available for multiple myeloma. Therefore, there is a high unmet medical need for therapies addressing new relevant molecular targets.
The foregoing release contains forward-looking statements that can be identified by words such as "will," "priority review," "underway," "ultimately," "potentially," "offer," "strategy," "can," "offers," "upcoming," "yet," "investigational," or similar terms, or by express or implied discussions regarding potential marketing approvals for LBH589, or regarding potential future revenues from LBH589. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that LBH589 will be approved for sale in any market where it has been submitted, or at any particular time. Neither can there be any guarantee that LBH589 will be submitted or approved for sale in any additional markets, or at any particular time. Nor can there be any guarantee that LBH589 will be commercially successful in the future. In particular, management's expectations regarding LBH589 could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
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 Richardson P, et al. Panorama 1: A Randomized, Double-blind, Phase 3 Study of Panobinostat or Placebo plus Bortezomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma. Abstract #8510. 50th American Society of Clinical Oncology (ASCO) Chicago, IL.
 Parkin M, et al. Global Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74-108.
 Pulte D, et al.Recent Improvement in Survival of Patients with Multiple Myeloma: Variation by Ethnicity, Leukemia and Lymphoma. 2013. Available at: http://informahealthcare.com/doi/abs/10.3109/10428194.2013.827188.
Accessed November 18, 2013.
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 U.S. Food and Drug Administration. For Consumers. Available at: http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm#priorityreview. Accessed May 2014.
 American Cancer Society. Multiple Myeloma. Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-it. Accessed May 2013.
 The Leukemia and Lymphoma Society. Myeloma. Revised 2013; 1:48.
 National Cancer Institute. What You Need to Know about Multiple Myeloma. Available at: http://www.cancer.gov/cancertopics/wyntk/myeloma. Accessed May 2013.
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