- Study of LBH589 plus bor­tez­o­mib and dexa­meth­a­sone met pri­mary end­point of extending PFS compared to bor­tez­o­mib plus dexa­meth­a­sone and placebo
- LBH589 has poten­tial to be the first in its class of anticancer agents avail­able to patients with multiple myeloma
- Data will be presented at an upcoming medical congress and discussed with regu­la­tory author­i­ties world­wide

Basel, Switzerland (Press Release) - Novartis today announced that results of a Phase III trial of the in­ves­ti­ga­tional com­­pound LBH589 (panobinostat) in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone, met the pri­mary end­point of sig­nif­i­cantly extending pro­gres­sion-free survival (PFS) in patients with re­lapsed or re­lapsed and refractory multiple myeloma when compared to bor­tez­o­mib plus dexa­meth­a­sone alone.

Full results from the PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) trial, con­tinue to be eval­u­ated and will be presented at an upcoming medical congress and discussed with regu­la­tory author­i­ties world­wide.

Multiple myeloma affects approx­i­mately 1 to 5 in every 100,000 people world­wide each year. The five year survival-rate for patients with the disease is about 44%[1].

LBH589 showed sig­nif­i­cant clin­i­cal benefit bringing it a step closer to becoming the first in its class of anti­cancer agents to be avail­able to patients with multiple myeloma. As a pan-deacetylase (pan-DAC) inhib­i­tor, LBH589 works by blocking a key cancer cell enzyme which ultimately leads to cellular stress and death of these cells[2].

"Results from this study show im­proved out­comes for these multiple myeloma patients who other­wise have few options to treat this incurable disease," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "Given its mech­a­nism of action, LBH589 has the poten­tial to be an im­por­tant treat­ment option for multiple myeloma."

Prior data dem­onstrated that oral LBH589, when com­bined with bor­tez­o­mib and dexa­meth­a­sone, re­cap­tures responses in heavily pre­treated and bor­tez­o­mib-refractory multiple myeloma patients, thereby provid­ing these patients with a poten­tial new option after failing prior standard treat­ments[3]. The com­­pound's possible benefits and risks are also being explored in addi­tional hema­to­logic malig­nan­cies through ongoing clin­i­cal trials.

Study Design

The PANobinostat ORAl in Multiple MyelomA (PANORAMA) clin­i­cal trial pro­gram is eval­u­ating LBH589 in patients with re­lapsed or re­lapsed and refractory multiple myeloma.

The PANORAMA-1 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. The pri­mary end­point of the trial was pro­gres­sion-free survival (PFS) and the key sec­ond­ary end­point is over­all survival (OS). Other sec­ond­ary end­points in­clude over­all response rate, duration of response and safety.

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 set of key enzymes which ultimately leads to cellular stress and death of these cells[2].

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 under­stand better 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[4].

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[4]. 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 "investigational," "potential," "will," "upcoming," "continue," "on-going," 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 submitted or approved for sale in any market, or at any particular time. Nor can there be any guar­an­tee that LBH589 will receive regu­la­tory approval or 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 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approx­i­mately USD 9.3 billion (USD 9.1 billion excluding im­pair­ment and amortization charges). Novartis Group com­pa­nies employ approx­i­mately 133,000 full-time equivalent asso­ci­ates and operate in more than 140 countries around the world. For more in­­for­ma­tion, please visit http://www.novartis.com.

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References

[1] 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.
[2] Novartis Data on File.
[3] Richardson PG, et al. PANORAMA 2: panobinostat in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone in patients with re­lapsed and bor­tez­o­mib-refractory myeloma. Blood. 2013; 122: 2331-2337.
[4] The Leukemia and Lymphoma Society. Myeloma. Revised 2013; 1:48.

Source: Novartis.