The U.S. Food and Drug Administration (FDA) has approved panobinostat (Farydak) in combination with bortezomib (Velcade) and dexamethasone for the treatment of patients with multiple myeloma. Panobinostat is the first histone deacetylase (HDAC) inhibitor approved to treat multiple myeloma. It is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent.
“[Panobinostat] 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,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “[Panobinostat’s] approval is particularly important because it has been shown to slow the progression of multiple myeloma.”
In November 2014, 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, Novartis Pharmaceuticals submitted additional information supporting panobinostat’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 Data
The safety and efficacy of panobinostat in combination with bortezomib and dexamethasone were demonstrated in 193 clinical trial participants with multiple myeloma who received at least two prior treatments that included bortezomib and an immunomodulatory agent. Participants were randomly assigned to receive a combination of panobinostat, bortezomib, and dexamethasone or bortezomib and dexamethasone alone.
Study results showed participants receiving the panobinostat combination had a median progression-free survival of about 10.6 months, compared to 5.8 months in participants treated with bortezomib and dexamethasone alone. Additionally, 59% of panobinostat-treated participants saw their cancer shrink or disappear after treatment vs 41% in those receiving bortezomib and dexamethasone.
Panobinostat carries a Boxed Warning alerting patients and health-care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiographic changes have occurred in patients receiving panobinostat. Because of these risks, the new 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 panobinostat 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 previously granted panobinostat Priority Review and Orphan Product designation. This approval 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. An improvement in survival or disease-related symptoms has not yet been established for panobinostat. The company is now required to conduct confirmatory trials to verify and describe the clinical benefit of panobinostat. ■