The U.S. Food and Drug Administration has approved the use of Farydak (panobinostat) for the treatment of patients with multiple myeloma who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. Farydak is to be used in combination with the chemotherapy bortezomib and the anti-inflammatory medication dexamethasone.
Farydak, made by Novartis, works by inhibiting the activity of histone deacetylases enzymes, which may slow the over-development of plasma cells in patients with multiple myeloma or cause the cells to die. Farydak is the first HDAC inhibitor approved to treat multiple myeloma.
"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, MD, Director of the FDA's Office of Hematology and Oncology Products, said in a news release. "Farydak's approval is particularly important because it has been shown to slow the progression of multiple myeloma."
Last November, the FDA's Oncologic Drugs Advisory Committee advised the agency that, based on the data reviewed, the drug's benefits did not outweigh its risks for patients with relapsed multiple myeloma. After the meeting, the company submitted additional information supporting Farydak's use for a different indication: patients with multiple myeloma who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent.
Clinical Trial Results
The safety and efficacy for Farydak in combination with bortezomib and dexamethasone was demonstrated in a clinical trial of 193 patients with multiple myeloma who had received at least two prior treatments that included bortezomib and an immunomodulatory agent. The data showed that patients receiving the combination had a progression-free survival time of 10.6 months compared with 5.8 months for patients receiving bortezomib and dexamethasone alone.
Additionally, 59 percent of the patients treated with Farydak had their cancer shrink or disappear versus only 41 percent of the patients receiving just bortezomib and dexamethasone.
Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes have occurred in patients receiving Farydak. Because of these risks, the drug is being approved with a Risk Evaluation and Mitigation Strategy (REMS) consisting of a communication plan to inform health care professionals of these risks and how to minimize them.
The most common side effects of Farydak were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, and weakness. The most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, increased creatinine, thrombocytopenia, leukopenia, and anemia. Health care professionals should also inform patients of the risk of bleeding in the gastrointestinal tract and the lungs, and hepatotoxicity, the FDA said.
The FDA had previously granted Farydak priority review and orphan product designation. Priority review provides for an expedited review of drugs that are intended to treat a serious disease or condition and may provide a significant improvement over available therapy. Orphan product designation is given to drugs intended to treat rare diseases.
The FDA action was taken under the agency's accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. The accelerated approval program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.
An improvement in survival or disease-related symptoms has not yet been established for Farydak. The company is now required to conduct confirmatory trials to verify and describe the clinical benefit of Farydak.