Novartis receives EU approval for Farydak®, the first in its class of anticancer agents approved for patients with multiple myeloma

NovartisNovartis 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].

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

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.

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. 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/. 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. 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. 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.

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