The FDA ( Food and Drug Administration ) has approved Farydak ( Panobinostat, previously known as LBH589 ) capsules in combination with Bortezomib ( Velcade ) 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.
Farydak has been shown to extend the progression-free survival ( PFS ) benefit of the standard-of-care therapy in this patient population.
Farydak is approved under accelerated approval based on progression-free survival. 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 ).
The trial found that the median progression-free survival 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 ] ).
The most common adverse reactions ( incidence greater than or equal to 20% ) in clinical studies are diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia and vomiting.
The most common non-hematologic laboratory abnormalities ( incidence greater than or equal to 40% ) are hypophosphatemia, hypokalemia, hyponatremia and increased creatinine.
The most common hematologic laboratory abnormalities ( incidence greater than or equal to 60% ) are thrombocytopenia, lymphopenia, leukopenia, neutropenia and anemia.
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 ( greater than or equal to 5% ) treatment-emergent serious adverse events 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.
Farydak is the first histone deacetylase ( HDAC ) inhibitor available to patients with multiple myeloma. As an HDAC inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.
Epigenetics is the cell programming that governs gene expression and cell development. 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.
Multiple myeloma impacts approximately 1 to 5 in every 100,000 people globally. ( Xagena )
Source: Novartis, 2015