• Farydak, an HDAC inhibitor with epigenetic activity, approved in combination for patients who received at least two prior regimens including bortezomib and IMiD[1]
• Farydak prolonged median PFS benefit when used with bortezomib and dexamethasone combination versus combination alone (from 6 to 11 months)[1]
• Multiple myeloma is an incurable blood cancer and there is an urgent need for new treatments[2]
• Farydak is approved under FDA's accelerated approval program; regulatory applications are underway in the EU, Japan and worldwide

Basel, Switzerland (Press Release) - Novartis announced today that the US Food and Drug Admin­istra­tion (FDA) has approved Farydak® (panobinostat, pre­vi­ously known as LBH589) capsules 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 immuno­modu­la­tory (IMiD) agent[1].

"Farydak rep­re­sents an exciting agent with a new mech­a­nism of action that is part of a promising class of drugs in this setting," said study investigator Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute. "Importantly, Farydak has been shown to im­prove pro­gres­sion-free survival in re­lapsed multiple myeloma patients who have received at least two prior regi­mens, in­­clud­ing bor­tez­o­mib and an IMiD, which is an area of particular unmet medical need."

Farydak has been shown to extend the pro­gres­sion-free survival (PFS) benefit of the standard-of-care ther­apy in this patient pop­u­la­tion[1]. Farydak is approved under accelerated approval based on PFS[1]. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firmatory trials. The FDA's accelerated approval pro­gram gives patients access to treat­ments for serious or life-threatening illnesses that provide meaningful thera­peutic benefit over existing treat­ments. The FDA has approved a risk evaluation and mitigation strategy (REMS) for Farydak. The REMS pro­gram serves to inform and educate health­care professionals about the risks that may be asso­ci­ated with Farydak treat­ment.

This FDA approval is based on efficacy and safety data in a pre-specified subgroup analysis of 193 patients who had received prior treat­ment with both 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)[1]. The trial found that the median PFS benefit in­­creased in Farydak patients who had received prior treat­ment with both bor­tez­o­mib and an IMiD (10.6 months; n=94), as compared to the placebo arm (5.8 months; n=99) (hazard ratio=0.52 [95% con­fi­dence in­ter­val (CI): 0.36, 0.76])[1].

The most common adverse reac­tions (incidence >= 20%) in clin­i­cal studies are diarrhea, fatigue, nausea, periph­eral edema, de­creased appetite, pyrexia and vomiting[1]. The most common non-hematologic laboratory ab­nor­mal­i­ties (incidence >= 40%) are hypophosphatemia, hypokalemia, hyponatremia and in­­creased creatinine[1]. The most common hema­to­logic laboratory ab­nor­mal­i­ties (incidence >= 60%) are thrombo­cytopenia, lymphopenia, leu­ko­penia, neu­tro­penia and anemia[1]. Farydak can cause fatal and serious toxicities in­­clud­ing severe diarrhea and cardiac toxicities. Severe diarrhea occurred in 25% of Farydak-treated patients. Severe and fatal cardiac ischemic events, in­­clud­ing severe arrhythmias and ECG changes have occurred in patients receiving Farydak. Serious adverse events (SAEs) occurred in 60% of patients treated with Farydak, bor­tez­o­mib and dexa­meth­a­sone compared to 42% of patients in the control arm. The most frequent (>= 5%) treat­ment-emergent SAEs reported for patients treated with Farydak were pneu­monia (18%), diarrhea (11%), thrombo­cytopenia (7%), fatigue (6%) and sepsis (6%). Additional serious adverse reac­tions in­cluded hemorrhage, myelosuppression, in­fec­tions, hepato­tox­ic­ity and embryo-fetal toxicity[1].

"Novartis is committed to devel­op­ing inno­va­tive first-in-class ther­a­pies for patients who need treat­ment options," said Bruno Strigini, Pres­i­dent, Novartis Oncology. "Farydak rep­re­sents a new drug class in multiple myeloma, providing these patients with an important treat­ment ap­proach for this dif­fi­cult-to-treat cancer."

Farydak is the first histone deacetylase (HDAC) inhibitor avail­able to patients with multiple myeloma[3]. As an HDAC inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma[4].

Additional regu­la­tory sub­missions for Farydak are being reviewed by health author­i­ties world­wide.

About multiple myeloma

Epigenetics is the cell pro­gramming that governs gene ex­pres­sion and cell devel­op­ment[3]. 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[5],[6].

Multiple myeloma impacts approx­i­mately 1 to 5 in every 100,000 people globally[7]. 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[8]. 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[2]. It typically occurs in individuals 60 years of age or older, with few cases in individuals younger than 40[9].

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.

Please see full Prescribing Information, in­­clud­ing Boxed WARNING, for Farydak® (panobinostat) capsules.

Outside of the US, Farydak (LBH589) is an inves­ti­ga­tional agent and has not been approved by regu­la­tory author­i­ties.

Disclaimer

The foregoing release con­tains forward-looking state­ments that can be identified by words such as "underway," "exciting," "promising," "committed," "being reviewed," "may," "contingent," "investigational," or similar terms, or by express or implied discussions regarding poten­tial future 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 approved for sale in any market where it has been submitted, 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 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, unexpected regu­la­tory actions or delays or gov­ern­ment reg­u­la­tion generally; the un­cer­tain­ties in­her­ent in research and devel­op­ment, in­­clud­ing 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 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 over-the-counter prod­ucts. 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 130,000 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.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis.

References
[1] Full Prescribing Information.
[2] The Leukemia and Lymphoma Society. Myeloma. Revised 2013;1:48.
[3] 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.
[4] Maes K, et al. Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma. Cancers. 2013;5:430-461.
[5] Smith EM, Boyd K, Davies FE. The Potential Role of Epigenetic Therapy in Multiple Myeloma. Br J Haematol. 2009;148:702-713.
[6] Muntean AG, Hess JL. Epigenetic Dysregulation in Cancer. Am J Pathol. 2009;175:1353-1361.
[7] Parkin M, et al. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
[8] American Cancer Society. Multiple Myeloma. Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003121-pdf.pdf. Accessed July 2014.
[9] National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Available at: http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed July 2014.

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

Source: Novartis