- Expanded indication allows for treatment of women whose
advanced ovarian cancer is associated with homologous recombination
deficiency (HRD)
- Zejula is now the only, once-daily PARP inhibitor approved as
monotherapy treatment for recurrent ovarian cancer beyond those
with a BRCA mutation in both the recurrent maintenance and
late-line treatment settings
GlaxoSmithKline (LSE/NYSE: GSK) today announced that the company
has received approval from the U.S. Food and Drug Administration
(FDA) for an expanded indication for Zejula (niraparib), an oral,
once-daily poly (ADP-ribose) polymerase (PARP) inhibitor for the
treatment of advanced ovarian, fallopian tube, or primary
peritoneal cancer patients, who have been treated with three or
more prior chemotherapy regimens and whose cancer is associated
with homologous recombination deficiency (HRD) positive status
defined by either:
- A deleterious or suspected deleterious BRCA mutation, or
- genomic instability and who have progressed more than six
months after response to the last platinum-based chemotherapy.
Patient selection is based on an FDA-approved companion diagnostic
for Zejula.
This represents the first time a PARP inhibitor has been
approved for use in patients beyond those with a BRCA-positive
(BRCA+) mutation as monotherapy in the late-line treatment setting.
Now women with late-line, HRD-positive (HRD+) disease are eligible
to be treated with a PARP inhibitor.
Axel Hoos, MD, PhD, SVP Oncology R&D, GSK, said: “This new
indication reinforces our commitment to providing treatment options
for more women impacted by ovarian cancer, especially those with
high unmet needs. We look forward to continuing our clinical
development program of Zejula and understanding its full potential
as a treatment for people living with ovarian cancer.”
This new indication is based on the QUADRA study, a Phase 2,
multi-center, open-label, single-arm clinical study representing a
real world, difficult-to-treat patient population with high unmet
needs. QUADRA is the largest clinical trial of a PARP inhibitor in
women who received three or more treatments for advanced ovarian
cancer. The trial enrolled a broad patient population including
women with BRCA+ platinum-sensitive, resistant and refractory
disease as well as women with HRD+ platinum-sensitive disease.
Clinically meaningful and durable benefit was demonstrated in
the FDA-indicated patient population with an objective response
rate (ORR) of 24% (95% CI, 16–34). A median duration of response
(mDOR) of 8.3 months (95% CI, 6.5–not estimable) was observed.
Additional analyses were conducted in various sub populations
where efficacy of Zejula was also demonstrated for patients with
tBRCA and GIS; defined as deleterious or suspected deleterious
somatic or germline BRCA mutation and genomic instability score
(GIS ≥42) as identified with Myriad’s myChoice® companion
diagnostic test, respectively:
- tBRCA+ platinum-sensitive disease, ORR of 39% (95% CI,
17,64);
- tBRCA+ platinum-resistant disease, ORR of 29% (95% CI,
11,52);
- tBRCA+ platinum-refractory disease, ORR of 19% (95% CI, 4,46);
or
- non-BRCA mut, GIS-positive, platinum-sensitive disease, ORR of
20% (95% CI, 8,37).
The safety profile was consistent with that seen in the Phase 3
NOVA trial in the recurrent maintenance population. Most common
grade ≥3 adverse reactions reported in ≥10% of patients in the
QUADRA study included thrombocytopenia (28%), anemia (27%),
neutropenia (13%) and nausea (10%).
Dr. Kathleen Moore, Lead Investigator of the QUADRA study;
Director, Oklahoma TSET Phase 1 Program; Associate Professor,
Section of Gynecologic Oncology, Stephenson Cancer Center,
University of Oklahoma, said: “Ovarian cancer has a high rate of
recurrence, so there is a real need for therapies for women whose
cancer has progressed through multiple lines of treatment and who
have few or no options left. It’s meaningful to see that Zejula has
been approved as a late-line treatment for women including those
with and without BRCA mutations.”
Ovarian cancer affects nearly 222,000 women in the U.S., and
approximately 85% of women with advanced ovarian cancer will see
the disease return. With each recurrence, the time a woman may
spend without her cancer progressing until the next recurrence gets
shorter. Currently, there are few effective options available for
treatment of platinum-resistant/refractory advanced ovarian cancer
or HRD+ ovarian cancer in the late-line setting. Zejula received
initial FDA approval in March 2017 for the maintenance treatment of
adult patients with recurrent epithelial ovarian, fallopian tube,
or primary peritoneal cancer, who are in a complete or partial
response to platinum-based chemotherapy. It is the only oral,
once-daily PARP inhibitor.
About QUADRA QUADRA is a large multi-center, open-label,
single-arm, Phase 2 registrational study that evaluated the safety
and activity of niraparib in adult patients with relapsed,
high-grade serous epithelial ovarian, fallopian tube, or primary
peritoneal cancer who were treated with three or more previous
chemotherapy regimens. Four hundred and sixty-three patients were
enrolled and received oral niraparib at a starting dose of 300 mg
once daily. Treatment was continued until disease progression. The
primary objective was the proportion of patients achieving an
investigator-assessed confirmed overall response in patients with
HRD+ tumors, including patients with BRCA and without BRCA
mutations, sensitive to their last platinum-based therapy.
Additional objectives of the study were to evaluate the efficacy of
niraparib in the broad late-line ovarian cancer population overall,
and in subgroups defined by clinical and molecular biomarkers, such
as platinum-sensitivity and BRCA+ and HRD status.
The Myriad myChoice companion diagnostic test was utilized
during this clinical trial and has been approved by the FDA as the
companion diagnostic test to determine HRD+ status as either tBRCA
and/or a genomic instability score (GIS ≥42). GIS is an algorithmic
measurement of Loss of Heterozygosity (LOH), Telomeric Allelic
Imbalance (TAI), and Large-scale State Transitions (LST).
Information about Myriad myChoice companion diagnostic is
available at Myriad.com.
About Ovarian Cancer Approximately 22,000 women are
diagnosed each year with ovarian cancer in the U.S. Ovarian cancer
is the fifth most frequent cause of cancer death among women.
Despite high response rates to platinum-based chemotherapy in the
front-line, approximately 85% of patients will experience disease
recurrence. Once the disease recurs, its considered incurable with
time to each future recurrence getting shorter. Late-line treatment
options for women with ovarian cancer are few, with the proportion
of patients achieving an overall response typically less than 10%
when treated with chemotherapy.
About Niraparib Niraparib is an oral, once-daily PARP
inhibitor that is currently being evaluated in multiple pivotal
trials. GSK is building a robust niraparib clinical development
program by assessing activity across multiple tumor types and by
evaluating several potential combinations of niraparib with other
therapeutics. The ongoing development program for niraparib
includes a Phase 3 trial as monotherapy maintenance treatment in
patients with first-line ovarian cancer (PRIMA), data from this
study were recently presented at the European Society for Medical
Oncology Congress (ESMO), a Phase 3 study as a first-line triplet
maintenance treatment in ovarian cancer (FIRST), and a Phase 2
study of niraparib combined with bevacizumab maintenance treatment
in advanced ovarian cancer (OVARIO).
Several combination studies are also underway, including trials
of niraparib plus pembrolizumab in metastatic, triple-negative
breast cancer and advanced, platinum-resistant ovarian cancer
(TOPACIO). Janssen Biotech has licensed rights to develop and
commercialize niraparib specifically for patients with prostate
cancer worldwide, except in Japan.
Important Safety Information
Zejula may cause serious side effects, including:
Bone marrow problems called Myelodysplastic Syndrome (MDS) or
a type of blood cancer called Acute Myeloid Leukemia (AML).
Some people who have ovarian cancer and who have received previous
treatment with chemotherapy or certain other medicines for their
cancer have developed MDS or AML during treatment with Zejula. MDS
or AML may lead to death.
Symptoms of low blood cell counts (low red blood cells, low
white blood cells, and low platelets) are common during
treatment with Zejula. They can be a sign of serious bone marrow
problems, including MDS or AML. These symptoms may include the
following:
- Weakness
- Feeling tired
- Weight loss
- Frequent infections
- Fever
- Shortness of breath
- Blood in urine or stool
- Bruising or bleeding more easily
Uncommonly, fever associated with low white blood cells is
observed during treatment with Zejula.
Your doctor will do blood tests to check your blood cell counts
before treatment with Zejula. You will be tested weekly for the
first month of treatment with Zejula, monthly for the next 11
months of treatment, and from time to time afterward.
High blood pressure is common during treatment with
Zejula, and it can become serious. Your doctor will check your
blood pressure and heart rate at least weekly for the first two
months, then monthly for the first year, and as needed thereafter
during your treatment with Zejula.
Before starting to take Zejula, tell your doctor about all of
your medical conditions, including if you:
- Have heart problems
- Have high blood pressure
- Are pregnant or plan to become pregnant. Zejula may harm an
unborn baby and may cause loss of pregnancy (miscarriage)
- If you are able to become pregnant, you should use effective
birth control (contraception) during treatment with Zejula and for
6 months after taking the last dose of Zejula
- If you are able to become pregnant, your doctor may perform a
pregnancy test before you start treatment with Zejula
- You should tell your doctor right away if you become
pregnant
- Are breastfeeding or plan to breastfeed
- Zejula may harm your baby. You should not breastfeed your baby
during treatment with Zejula and for 1 month after taking the last
dose of Zejula
Tell your doctor about all the medicines you take,
including prescription and over-the-counter medicines, vitamins,
and herbal supplements.
The most common side effects of Zejula include the
following:
- Heart not beating regularly
- Nausea
- Constipation
- Vomiting
- Pain in the stomach area
- Mouth sores
- Diarrhea
- Indigestion or heartburn
- Dry mouth
- Tiredness
- Loss of appetite
- Urinary tract infection
- Shortness of breath
- Cough
- Rash
- Changes in liver function or other blood tests
- Pain in your joints, muscles, and back
- Headache
- Dizziness
- Change in the way food tastes
- Trouble sleeping
- Anxiety
- Sore throat
- Changes in the amount or color of your urine
If you have certain side effects, then your doctor may change
your dose of Zejula, temporarily stop, or permanently stop
treatment with Zejula.
These are not all the possible side effects of Zejula. For more
information, ask your doctor or pharmacist. Call your doctor for
medical advice about side effects. You may report side effects to
FDA at 1-800-FDA-1088.
For full prescribing information visit
www.zejula.com/prescribing-information.
myChoice companion diagnostic is a registered trademark of
Myriad.
About GSK Oncology GSK is focused on maximizing patient
survival through transformational medicines. GSK’s pipeline is
focused on immuno-oncology, cell therapy, cancer epigenetics and
synthetic lethality. Our goal is to achieve a sustainable flow of
new treatments based on a diversified portfolio of investigational
medicines utilizing modalities such as small molecules, antibodies,
antibody drug conjugates and cells, either alone or in
combination.
About GSK GSK is a science-led global healthcare company
with a special purpose: to help people do more, feel better, live
longer. For further information please visit www.gsk.com.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or
projections made by GSK, including those made in this announcement,
are subject to risks and uncertainties that may cause actual
results to differ materially from those projected. Such factors
include, but are not limited to, those described under Item 3.D
'Principal risks and uncertainties' in the company's Annual Report
on Form 20-F for 2018.
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