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.
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