FDA Approves Panobinostat for Treatment of Multiple Myeloma
Intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent
On 23 February 2015, the US Food and Drug Administration (FDA) approved panobinostat (Farydak) for the treatment of patients with multiple myeloma. It inhibits the activity of histone deacetylases (HDACs) and is the first HDAC inhibitor approved to treat multiple myeloma. Panobinostat is intended for patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent. It is to be used in combination with chemotherapy drug bortezomib and dexamethasone – an anti-inflammatory medication.
“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,” said Dr Richard Pazdur, director of the Office of Hematology and Oncology Products at the FDA’s Center for Drug Evaluation and Research. “Farydak’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, the company 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.
The safety and efficacy of panobinostat in combination with bortezomib and dexamethasone was 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 that participants receiving the panobinostat combination had progression-free survival of 10.6 months, compared to 5.8 months in participants treated with bortezomib and dexamethasone alone. Additionally, 59% of panobinostat-treated participants achieved response after treatment, versus 41% in those receiving bortezomib and dexamethasone.
Panobinostat carries a Boxed Warning alerting patients and health care professionals that severe diarrhoea and severe and fatal cardiac events, arrhythmias and electrocardiogram changes have occurred in patients receiving panobinostat. Because of these risks, panobinostat is being approved with a Risk Evaluation and Mitigation Strategy consisting of a communication plan to inform health care professionals of these risks and how to minimise them.
The most common side effects of panobinostat were diarrhoea, tiredness, nausea, peripheral oedema, decreased appetite, fever, vomiting and weakness. The most common laboratory abnormalities were hypophosphataemia, hypokalaemia, hyponatraemia, increased creatinine, thrombocytopaenia, leukopaenia and anaemia. Healthcare professionals should also inform patients of the risk of bleeding in the gastrointestinal tract and the lungs, and hepatotoxicity.
The FDA granted panobinostat 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 programme, 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 programme 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 panobinostat. The company is now required to conduct confirmatory trials to verify and describe the clinical benefit of panobinostat.
Farydak is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals.