FDA Approves Farydak for Multiple Myeloma

The Food and Drug Administration (FDA) has approved Farydak (panobinostat) in combination with Velcade (bortezomib) and dexamethasone for patients with multiple myeloma who receive prior treatment with Velcade and an immunomodulatory (IMiD) agent, based on a subgroup analysis from the PANORAMA-1 trial.

In the prespecified analysis of the phase 3 trial that included 193 patients who were pretreated with Velcade and an IMiD, the median progression-free survival (PFS) with the Farydak combination was 10.6 months versus 5.8 months with placebo. Additionally, the tumor shrinkage rate with Farydak was 59 percent versus 41 percent with Velcade and dexamethasone alone.

Farydak was approved with a warning regarding severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes. As a result of these side effects, the drug has also been approved along with a Risk Evaluation and Mitigation Strategy (REMS).

“Farydak has a new mechanism of action that distinguishes it from prior drugs approved to treat multiple myeloma, making it a potentially attractive candidate agent for the treatment of multiple myeloma,” Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a release. “Farydak’s approval is particularly important because it has been shown to slow the progression of multiple myeloma.”

The PANORAMA-1 study randomized 768 patients at a median age of 63 with relapsed or relapsed multiple myeloma to receive Velcade and dexamethasone with Farydak or placebo. Treatment was administered in two 24-week phases.

Study participants had been treated with up to three prior therapies, with 48 percent receiving at least two regimens. The most common prior treatments in the Farydak arm were corticosteroids, melphalan, stem cell transplant, Thalomid (thalidomide), cyclophosphamide and Velcade.

Treatment with the 3-drug Farydak regimen improved the primary endpoint of PFS by 3.9 months compared with Velcade and dexamethasone alone. By independent review, the median PFS was 9.9 months with Farydak versus 7.7 months without it. The overall response rate was 64 percent with Farydak and 54 percent with placebo. The complete response rate was 12 percent versus 7 percent and the duration of response was 11.8 versus 9.7 months, for Farydak and placebo, respectively.

Prior to the approval, the FDA extended the review period for the HDAC inhibitor by three months following a 5 to 2 vote against the approval from the FDA’s Oncologic Drugs Advisory Committee (ODAC). The majority of concerns from the advisory panel related to long-term survival data and the side effect profile.

The most common side effects for Farydak were thrombocytopenia, diarrhea, fatigue and pneumonia. Serious adverse events were more common with Farydak versus placebo.

New data presented at the 2014 Annual Meeting of the American Society of Hematology shed light on the long-term benefits of the Farydak combination. At this analysis, the median OS was 38.2 and 35.4 months, respectively, for the Farydak and control arms.

A higher number of patients discontinued treatment in the Farydak arm compared with placebo as a result of adverse events or consent withdrawal. However, 40 percent of patients in the placebo arm stopped therapy as a result of progression compared with 21 percent in the Farydak arm.

Clinical trials continue to investigate the safety and efficacy of Farydak across a variety of settings. A phase 1/2 study is exploring the combination of Revlimid (lenalidomide), Velcade and dexamethasone plus Farydak as a treatment for transplant eligible newly diagnosed patients with multiple myeloma. Additionally, the drug is being explored in combination with other proteasome inhibitors, namely Kyprolis (carfilzomib).