Novartis data in The Lancet Oncology show LBH589 offers 4-month increase in median PFS for patients with multiple myeloma
Sep 19, 2014
Results show statistically significant and clinically relevant increase in median progression-free survival with LBH589 plus bortezomib and dexamethasone
LBH589, a first-in-class treatment for patients with relapsed/refractory multiple myeloma if approved, helps extend benefit of standard-of-care therapy
First Phase III study to demonstrate superiority of a three-drug over two-drug combination in this patient population
Multiple myeloma, the second most common blood cancer, is incurable; most patients will relapse or become refractory so new treatments are needed,
Basel, September 19, 2014 - Data published today in The Lancet Oncology demonstrated a statistically significant and clinically relevant 4-month improvement in median progression-free survival (PFS) (hazard ratio=0.63 [95% confidence interval (CI): 0.52 to 0.76]; p<0.0001) for patients with relapsed or relapsed and refractory multiple myeloma when using the investigational compound LBH589 (panobinostat) in combination with bortezomib* and dexamethasone compared to placebo plus the same combination. 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.
About PANORAMA-1 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.
About LBH589 and its epigenetic role in multiple myeloma 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.
Disclaimer The foregoing release contains forward-looking statements that can be identified by words such as "offers," "will," "investigational," "increasing," "ultimately," "potential," "committed," "priority review," "underway," "may," "offer," "yet," 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.
About Novartis Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.
* Trade name Velcade® registered to Millennium Pharmaceuticals, Inc.
References  San-Miguel J, et al. Randomized Phase 3 Trial of Panobinostat Plus Bortezomib and Dexamethasone Versus Placebo Plus Bortezomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma. The Lancet Oncology. 2014.  National Cancer Institute. A Snapshot of Multiple Myeloma. Available at: http://www.cancer.gov/researchandfunding/snapshots/myeloma. Accessed July 2014.  Richardson P, Mitsiades C, Schlossman R, et al. The Treatment of Relapsed and Refractory Multiple Myeloma. Hematology. 2007;317-323.  Parkin M, et al. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005;55:74-108.  National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed July 2014.  US Food and Drug Administration. For Consumers.  American Cancer Society. Multiple Myeloma. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf. Accessed July 2014.  The Leukemia and Lymphoma Society. Myeloma. Revised 2013;1:48.  Grønbæk K, Treppendahl M, Asmarand F, Guldberg P. Epigenetic Changes in Cancer as Potential Targets for Prophylaxis and Maintenance Therapy. Basic & Clinical Pharmacology & Toxicology. 2008;103:389-396.  Smith EM, Boyd K, Davies FE. The Potential Role of Epigenetic Therapy in Multiple Myeloma. Br J Haematol. 2009;148:702-713.  Muntean AG, Hess JL. Epigenetic Dysregulation in Cancer. Am J Pathol. 2009;175:1353-1361.  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) 2014 Chicago, IL.  Maes K, et al. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma. Cancers. 2013;5:430-461
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