• Farydak (panobinostat) combination is approved in the EU for patients with multiple myeloma who received >=2 prior regimens including bortezomib and IMiD[1]
• In clinical trials, Farydak combination increased PFS by 7.8 months in patients who received >=2 prior regimens, including bortezomib and an IMiD[1]
• As the first HDAC inhibitor approved in the EU for multiple myeloma, Farydak may help reset key cell function in multiple myeloma through epigenetic activity[2]
• Farydak is approved in the US and Japan for certain patients with previously treated multiple myeloma; indications vary by country

Basel, Switzerland (Press Release) - Novartis announced today that the European Com­mis­sion has ap­proved Farydak® (panobinostat, pre­vi­ously known as LBH589) capsules, in com­bi­na­tion with bor­tez­o­mib* and dex­a­meth­a­sone, for the treat­ment of adult patients with re­lapsed and/or refractory multiple myeloma who have received at least two prior regi­mens in­­clud­ing bor­tez­o­mib and an immuno­modu­la­tory agent (IMiD). The approval of Farydak marks the first time a histone deacetylase (HDAC) inhibitor with epigenetic activity is avail­able in the European Union (EU), providing a new treat­ment option for patients living with multiple myeloma whose disease has progressed after standard-of-care ther­apy[1,2].

"Farydak is a welcome ad­vance for people living with re­lapsed and/or refractory multiple myeloma in Europe," said Philippe Moreau, MD, Department of Hematology, Centre Hospitalier Universitaire de Nantes, France. "Patients with multiple myeloma often relapse or stop responding to treat­ments; Farydak offers a new mech­a­nism of action, which may im­prove the effectiveness of response to standard-of-care treat­ment in patients."

Multiple myeloma is a cancer of the plasma cells, a type of white blood cell present in the bone marrow, and affects approx­i­mately 84,000 people in Europe[3,4]. Farydak is the first HDAC inhibitor to show efficacy in multiple myeloma[5]. As an HDAC inhibitor, its epigenetic activity may help restore cell function in patients with multiple myeloma[2].

The EU approval of Farydak is based on efficacy and safety data in a subgroup analysis of 147 patients who had received at least two prior regi­mens, in­­clud­ing bor­tez­o­mib and an IMiD, during the Phase III, ran­dom­ized, double-blind, placebo-controlled, multi­center global registration trial, called PANORAMA-1 (PANo­bino­stat ORAl in Multiple MyelomA), eval­u­ating Farydak in com­bi­na­tion with bor­tez­o­mib and dex­a­meth­a­sone against bor­tez­o­mib and dex­a­meth­a­sone alone in patients with re­lapsed and/or re­lapsed and refractory multiple myeloma. The trial found that the median pro­gres­sion-free survival (PFS) benefit in this subgroup in­­creased by 7.8 months in Farydak patients who had received prior treat­ment with both bor­tez­o­mib and an IMiD (12.5 months; n=73), as compared to the placebo arm (4.7 months; n=74) (hazard ratio=0.47 [95% con­fi­dence in­ter­val (CI): 0.31, 0.72])[1].

The most common non-hematological adverse reac­tions in­cluded diarrhea, fatigue, nausea and vomiting. treat­ment-emergent hema­to­logical toxicities in­cluded throm­bo­cytopenia, anemia, neu­tro­penia and lym­pho­penia. QTc prolongation of >480 and <500 msec was recorded in 1.3% of patients and change from base­line of >60 msec was observed in 0.8% of patients. No patients had an absolute QTc prolongation of >500 msec. Cardiac events (most frequently atrial fibrillation, tachycardia, palpitation and sinus tachycardia) were re­ported in 17.6% of the Farydak-treated patients versus 9.8% of placebo-treated patients and syncope events were reported in 6.0% versus 2.4%. Discontinuation due to adverse events (AEs), re­gard­less of cau­sal­i­ty, was observed in 36.2% of patients. The most common AEs leading to treat­ment dis­con­tinu­a­tion were diarrhea (4.5%), asthenia and fatigue (2.9% each) and pneu­monia (1.3%). On treat­ment deaths not due to the study indi­ca­tion (multiple myeloma) were reported in 6.8% of Farydak-treated patients versus 3.2% of placebo-treated patients[1].

"With the approval of Farydak in the European Union, we hope to address critically important treat­ment needs faced by the multiple myeloma com­munity-disease pro­gres­sion and treat­ment resistance," said Bruno Strigini, Pres­i­dent, Novartis Oncology. "This mile­stone, the approval of a first in its class treat­ment option for patients in need of new ther­a­pies, is the result of more than 13 years of dedicated research, which has helped us better under­stand the devel­op­ment of multiple myeloma."

Farydak in com­bi­na­tion with bor­tez­o­mib and dex­a­meth­a­sone is also approved in the US, Chile and Japan for certain patients with pre­vi­ously treated multiple myeloma. The exact indi­ca­tion for Farydak varies by country. In the US, Farydak is approved in com­bi­na­tion with bor­tez­o­mib and dex­a­meth­a­sone for the treat­ment of patients with multiple myeloma who have received at least two prior regi­mens, in­­clud­ing bor­tez­o­mib and an IMiD. Continued approval in the US may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials.

About multiple myeloma

Multiple myeloma impacts approx­i­mately 84,000 people in Europe[4]. 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[3]. Multiple myeloma is an incurable disease with a high rate of relapse (when the can­cer returns) and resistance (when the ther­apy stops work­ing)[6]. Standard-of-care regi­mens of pro­tea­some inhibitors and IMiDs are often used to treat multiple myeloma, but most patients will stop responding to these treat­ments creating an unmet need for new options with novel mech­a­nisms of action[6,7,8]. Multiple myeloma typically occurs in individuals 60 years of age or older, with few cases in indi­vid­u­als younger than 40[9].

About the PANORAMA Clinical Trial Program

PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) is a Phase III, ran­dom­ized, double-blind, placebo-controlled, multi­center global registration trial to eval­u­ate panobinostat 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 making it the largest global registration trial for multiple myeloma to date. The pri­mary end­point of the trial was 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[10].

Farydak® Important Safety Information

Farydak can cause serious side effects, in­­clud­ing diarrhea and heart problems.

Diarrhea is common with Farydak and can be severe. Patients should tell their health­care provider (HCP) right away if they have abdominal (stomach) cramps, loose stool, diarrhea, or feel like they are becoming dehydrated. HCPs may prescribe medicines to help prevent or treat these side effects. Taking or using stool softeners or laxative medicines may worsen diarrhea, patients should talk to their HCP before taking or using these medicines.

Farydak can cause severe heart problems which can lead to death. Risk of heart problems may be in­­creased with a con­di­tion called "long QT syn­drome" or other heart problems. Patients should call their HCP and get emergency medical help right away if they have any of the fol­low­ing symp­toms of heart problems: chest pain, faster or slower heart beat, palpitations (feel like heart is racing), feel lightheaded or faint, dizzi­ness, blue colored lips, shortness of breath, or swelling in legs.

Farydak can cause severe bleeding which can lead to death. It may take patients longer than usual to stop bleed­ing while taking Farydak. Patients should tell their HCP right away if they get any of the fol­low­ing signs of bleed­ing: blood in stools or black stools (look like tar), pink or brown urine, unexpected bleed­ing or bleed­ing that is severe or that cannot be controlled, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, in­­creased bruising, feeling dizzy or weak, confusion, change in speech, or headache that lasts a long time.

Farydak is a prescription medicine used, in com­bi­na­tion with bor­tez­o­mib and dex­a­meth­a­sone, to treat people with a type of can­cer called multiple myeloma after at least two other types of treat­ment have been tried. It is not known if Farydak is safe and effective in children.

Patients should tell their HCP about all of the medicines they take, in­­clud­ing prescription and over-the-counter medicines, vitamins and herbal supple­ments.

Patients should take Farydak exactly as the HCP tells them to take it. The HCP will tell patients how much Farydak to take and when to take it. The HCP may change the dose or stop treat­ment temporarily if patients ex­peri­ence side effects. Patients should not change the dose or stop taking Farydak without first talking with their HCP.

Patients should avoid eating star fruit, pomegranate or pomegranate juice, and grapefruit or grapefruit juice while taking Farydak. These foods may affect the amount of Farydak in the blood.

Low blood cell counts are common with Farydak and can be severe. Low platelet count (thrombocytopenia) can cause unusual bleeding or bruising under the skin. Low white blood cell count (neutropenia) can cause in­fec­tions. Low red blood cell count (anemia) may make a patient feel weak, tired, or they may get tired easily, look pale, or feel short of breath.

There is an in­­creased risk of in­fec­tion while taking Farydak. Patients should contact their HCP right away if they have a fever or have any signs of an in­fec­tion in­­clud­ing sweats or chills, cough, flu-like symp­toms, shortness of breath, blood in phlegm, sores on body, warm or painful areas on body, or feeling very tired.

Patients should call their HCP right away with any of the fol­low­ing symp­toms of liver problems: feel tired or weak, loss of appetite, dark amber colored urine, upper abdominal pain, yellowing of skin or the white of eyes.

The most common side effects of Farydak in­clude tiredness, nausea, swelling in arms or legs, de­creased appetite, fever and vomiting. Patients should tell their HCP if they have any side effect that is bothersome or that does not go away.

* Trade name Velcade® registered to Millennium Pharma­ceu­ticals, Inc.

Disclaimer

The foregoing release con­tains forward-looking state­ments that can be identified by words such as "may," "hope," "contingent," "will," or similar terms, or by express or implied discussions regarding poten­tial addi­tional market­ing approvals for Farydak, or regarding poten­tial future revenues from Farydak. 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 Farydak will be submitted or approved for sale in any addi­tional markets, or at any particular time. Neither can there be any guar­an­tee that Farydak will be submitted or approved for any addi­tional indi­ca­tions or labeling in any market, or at any particular time. Nor can there be any guar­an­tee that Farydak will be commercially successful in the future. Continued approval of Farydak in the approved indi­ca­tion in the US may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials. In particular, man­agement's ex­pec­ta­tions regarding Farydak could be affected by, among other things, the un­cer­tain­ties in­her­ent in research and devel­op­ment, in­­clud­ing unexpected regu­la­tory actions or delays or gov­ern­ment reg­u­la­tion generally; unexpected clin­i­cal trial results and addi­tional analysis of existing clin­i­cal data; 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 safety issues; 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 and cost-saving generic pharma­ceu­ticals. Novartis is the only global com­pany with leading positions in these areas. In 2014, the Group achieved net sales of USD 58.0 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 120,000 full-time-equivalent asso­ci­ates. Novartis prod­ucts are avail­able in more than 180 countries around the world. For more in­­for­ma­tion, please visit http://www.novartis.com.

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References

[1.] Farydak® (panobinostat): EU Summary of Product Characteristics. Novartis; Aug 2015.
[2.] Maes K, et al. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma. Cancers. 2013;5:430-461.
[3.] American Cancer Society. Multiple Myeloma. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf (link is external). Accessed July 2015.
[4.] Myeloma Patients Europe. A Report on Myeloma Patient Perspectives. 2013. Available at http://www.mpeurope.org/publications/reports-and-position-statements/ (link is external). Accessed July 2015.
[5.] 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.
[6.] The Leukemia and Lymphoma Society. Myeloma. Revised 2013;1:48.
[7.] National Cancer Institute. A Snapshot of Multiple Myeloma. Available at: http://www.cancer.gov/researchandfunding/snapshots/myeloma (link is external). Accessed July 2015.
[8.] Richardson P, Mitsiades C, Schlossman R, et al. The treat­ment of Relapsed and Refractory Multiple Myeloma. Hematology. 2007;317-323.
[9.] National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html (link is external). Accessed July 2015.
[10.] 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;15:1195-1206.

Source: Novartis.