FDA. US: The U.S. Food and Drug Administration today approved Farydak (panobinostat) for the treatment of patients with multiple myeloma.
Multiple
myeloma is a form of blood cancer that arises from plasma cells, a type
of white blood cell, found in bone marrow. According to the National
Cancer Institute, approximately 21,700 Americans are diagnosed with
multiple myeloma and 10,710 die from the disease annually.
Primarily
affecting older adults, multiple myeloma causes plasma cells to rapidly
multiply and crowd out other healthy blood cells from the bone marrow.
When the bone marrow has too many plasma cells, the cells may move to
other parts of the body, which can weaken the body’s immune system, lead
to anemia and cause other bone and kidney problems.
Farydak works
by inhibiting the activity of enzymes, known as histone deacetylases
(HDACs). This process may slow the over-development of plasma cells in
multiple myeloma patients or cause these dangerous cells to die.
Farydak
is the first 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. Farydak
is to be used in combination with bortezomib, a type of chemotherapy,
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 Richard Pazdur,
M.D., director of the Office of Hematology and Oncology Products in 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 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.
The safety and efficacy of Farydak 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
Farydak, bortezomib and dexamethasone, or bortezomib and dexamethasone
alone.
Study results showed participants receiving the Farydak
combination saw a delay in their disease progression (progression-free
survival) for about 10.6 months, compared to 5.8 months in participants
treated with bortezomib and dexamethasone alone. Additionally, 59
percent of Farydak-treated participants saw their cancer shrink or
disappear after treatment (response rate), versus 41 percent in those
receiving 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 (ECG) changes have occurred in patients receiving
Farydak. Because of these risks, Farydak 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 low levels of phosphorus in the blood
(hypophosphatemia), low potassium levels in the blood (hypokalemia), low
levels of salt in the blood (hyponatremia), increased creatinine, low
platelets (thrombocytopenia), low white blood cell counts (leukopenia)
and low red blood cell counts (anemia). Healthcare professionals should
also inform patients of the risk of bleeding in the gastrointestinal
tract and the lungs, and liver damage (hepatotoxicity).
The FDA
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.
Farydak is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals.
The
FDA, an agency within the U.S. Department of Health and Human Services,
promotes and protects the public health by, among other things,
assuring the safety, effectiveness, and security of human and veterinary
drugs, vaccines and other biological products for human use, and
medical devices. The agency also is responsible for the safety and
security of our nation’s food supply, cosmetics, dietary supplements,
products that give off electronic radiation, and for regulating tobacco
products.