The
U.S. Food and Drug Administration today granted accelerated approval to
Lynparza (olaparib), a new drug treatment for women with advanced
ovarian cancer associated with defective BRCA genes, as detected by an
FDA-approved test.Ovarian cancer forms in the ovary, one of a
pair of female reproductive glands where ova, or eggs, are formed. The
National Cancer Institute estimates that 21,980 American women will be
diagnosed with and 14,270 will die from ovarian cancer in 2014.
Ovarian cancer risk factors
Ovarian cancer symptoms
Lynparza
is a poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes
involved in repairing damaged DNA. It is intended for women with heavily
pretreated ovarian cancer that is associated with defective BRCA genes.
“Today’s
approval constitutes the first of a new class of drugs for treating
ovarian cancer,” said Richard Pazdur, MD, director of the Office of
Hematology and Oncology Products in the FDA’s Center for Drug Evaluation
and Research. “Lynparza is approved for patients with specific
abnormalities in the BRCA gene and is an example of how a greater
understanding of the underlying mechanisms of disease can lead to
targeted, more personalized treatment.
The FDA approved Lynparza
with a genetic test called BRACAnalysis CDx, a companion diagnostic that
will detect the presence of mutations in the BRCA genes (gBRCAm) in
blood samples from patients with ovarian cancer. The BRCA genes are
involved with repairing damaged DNA and normally work to suppress tumor
growth. Women with mutations resulting in defective BRCA genes are more
likely to get ovarian cancer, and it is estimated that 10 to 15 percent
of all ovarian cancer is associated with these hereditary BRCA
mutations.
The FDA evaluated the BRACAnalysis CDx’s safety and
efficacy under the agency’s premarket approval pathway used for
high-risk medical devices. Until now, the manufacturer, a clinical
laboratory, had been marketing this test, although not specifically for
use as a companion diagnostic, without FDA approval as a laboratory
developed test (LDT), which is a test that is designed, manufactured and
used in a single laboratory. The new test is approved as a companion
diagnostic, specifically to identify patients with advanced ovarian
cancer who may be candidates for treatment with Lynparza.
“The
approval of safe and effective companion diagnostic tests and drugs
continue to be important developments in oncology,” said Alberto
Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and
Radiological Health in the FDA’s Center for Devices and Radiological
Health. “We are very excited that the BRACAnalysis CDx is the FDA’s
first approval of an LDT under a premarket approval application and is
the first approval of an LDT companion diagnostic. The use of companion
diagnostics helps bring to market safe and effective treatments specific
to a patient’s needs.”
The FDA’s approval of the BRACAnalysis CDx
is based on data from the clinical study used to support approval of
Lynparza. Blood samples from clinical trial participants were tested to
validate the test’s use for detecting BRCAmutations in this population.
Lynparza’s
efficacy was examined in a study where 137 participants with
gBRCAm-associated ovarian cancer received the drug. The study was
designed to measure objective response rate (ORR), or the percentage of
participants who experienced partial shrinkage or complete disappearance
of the tumor. Results showed 34 percent of participants experienced ORR
for an average of 7.9 months.
Common side effects of Lynparza
included nausea, fatigue, vomiting, diarrhea, distorted taste
(dysgeusia), indigestion (dyspepsia), headache, decreased appetite,
common cold-like symptoms (nasopharyngitis), cough, joint paint
(arthralgia), musculoskeletal pain, muscle pain (myalgia), back pain,
rash (dermatitis) and abdominal pain. Serious side effects included the
development of myelodysplastic syndrome, a condition where the bone
marrow is unable to produce enough functioning blood cells; acute
myeloid leukemia, a bone marrow cancer; and lung inflammation.
The
most common laboratory abnormalities were increased creatinine,
increased average volume of red blood cells (mean corpuscular volume
elevation), decreased red blood cell count (hemoglobin), decreased white
blood cell count (lymphocytes and neutrophils) and decreased platelet
levels.
In June, Lynparza was reviewed by the FDA’s Oncologic
Drugs Advisory Committee for potential use as maintenance therapy
(treatment given to keep cancer from returning). The committee advised
the agency in a vote of 11 to 2 that the data did not support Lynparza’s
accelerated approval for this use. After the meeting, the company
submitted additional information supporting Lynparza’s use for a
different use: in patients with gBRCAm-associated ovarian cancer who
have received three or more chemotherapy treatments.
The FDA is
approving Lynparza 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. This program provides earlier patient access to promising new
drugs while the company conducts confirmatory clinical trials.
Lynparza’s application was reviewed under the FDA’s priority review
program, which provides for an expedited review of drugs that are
intended to treat a serious disease or condition and, if approved, would
offer significant improvement compared to marketed products.
BRACAnalysis
CDx’s application was reviewed under the FDA’s priority review program
for devices, which provides for priority review of devices that meet
certain criteria, including that the devices are intended to treat or
diagnose a life-threatening or irreversibly debilitating disease or
condition and, if approved, would offer significant, clinically
meaningful advantages compared to marketed products.
Lynparza is
marketed by AstraZeneca Pharmaceuticals, based in Wilmington, Delaware.
BRACAnalysis CDx is manufactured by and performed at Salt Lake City,
Utah-based Myriad Genetic Laboratories, Inc.