Novartis announced today that the US Food and Drug Administration (FDA) has approved Farydak® (panobinostat) in combination with Velcade® and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior regimens, including Velcade® and an immunomodulatory (IMiD) agent.
The FDA approval was partially based on the results of the phase III PANORAMA1 trial reported in late 2014 in The Lancet Oncology. In this study San-Miguel and colleagues found that adding the pan-deacetylase inhibitor Farydak® to Velcade® and dexamethasone improved progression-free survival in patients with relapsed or relapsed and refractory multiple myeloma.
Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.
Farydak® is a drug that belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division and cause cell death. It is being studied in myeloma as well as other blood cancers and solid tumors. Early studies have shown that Farydak® in combination with Velcade more effectively kills myeloma cells than either drug alone.
In the PANORAMA1 trial 768 patients from 215 centers in 34 countries who had relapsed or relapsed and refractory multiple myeloma were treated with either Farydak®, Velcade, and dexamethasone or a standard treatment regimen of Velcade, and dexamethasone and directly compared.
Patients in the Farydak® treatment group were more likely to experience diarrhea and low platelet and white blood cell counts often resulting in the discontinuation of treatment. Farydak® treated patients however experienced an improvement in time to cancer progression from 8 to 12 months with over twice as many patients surviving 2 years from treatment.
Although Farydak® was associated with more toxicity especially to the bone marrow, its addition to a Velcade treatment regimen clearly improved time to cancer progression. Longer follow up is required to determine any overall survival benefit. Use of Farydak® earlier in the management of myeloma will likely be associated with fewer side effects.
Reference: San-Migule J, Hungira V, Yoon S-S, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. The Lancet Oncology, Volume 15, Issue 11, Pages 1195 – 1206, October 2014.