• Results show adding LBH589 to bortezomib and dexamethasone significantly improved PFS by 37%, meeting Phase III study primary endpoint[1]
• 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[1]
• 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[1]
• Based on these data, US FDA granted priority review in May; additional global regulatory filings are underway

Basel, Switzerland (Press Release) - 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]. 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)[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) on June 14 in Milan, Italy.

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[1].

About LBH589

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[4].

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[6].

Multiple myeloma typically occurs in individuals 50 years of age and older, with few cases in individuals younger than 40[7]. 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[8]. There are cur­rently no curative ther­a­pies avail­able for multiple myeloma[7]. Therefore, there is a high unmet medical need for ther­a­pies addressing new relevant molecular targets.

Disclaimer

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.

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 and diagnostic tools, 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 operate in more than 150 countries around the world. For more in­­for­ma­tion, please visit http://www.novartis.com.

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References
[1] 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.
[2] Parkin M, et al. Global Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74-108.
[3] 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.
[4] Novartis Data on File.
[5] U.S. Food and Drug Admin­istra­tion. For Consumers. Available at: http://www.fda.gov/forconsumers/byaudience/forpatientadvocates/speedingaccesstoimportantnewtherapies/ucm128291.htm#priorityreview. Accessed May 2014.
[6] American Cancer Society. Multiple Myeloma. Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-it. Accessed May 2013.
[7] The Leukemia and Lymphoma Society. Myeloma. Revised 2013; 1:48.
[8] National Cancer Institute. What You Need to Know about Multiple Myeloma. Available at: http://www.cancer.gov/cancertopics/wyntk/myeloma. Accessed May 2013.

Source: Novartis.