REG - GSK PLC - US FDA ODAC review of Zejula Phase III NOVA trial

GSKAnnouncement

22/09/2022 14:00

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RNS Number : 3466A  GSK PLC  22 September 2022

Issued: 22 September 2022, London UK

 

Oncologic Drugs Advisory Committee to review Zejula overall survival data from
the NOVA phase III trial in recurrent ovarian cancer

 

 

GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug
Administration (FDA) will convene a meeting of the Oncologic Drugs Advisory
Committee (ODAC) to discuss overall survival (OS) data from the
ENGOT-OV16/NOVA phase III clinical trial. NOVA is a randomised, double-blind,
placebo-controlled phase III trial of Zejula (niraparib), an oral, once-daily
poly (ADP-ribose) polymerase (PARP) inhibitor for the maintenance treatment of
women with platinum-sensitive recurrent ovarian cancer.

 

The phase III NOVA trial met the primary endpoint of progression-free survival
(PFS) in both the gBRCAm and non-gBRCAm cohorts, demonstrating a statistically
significant and clinically meaningful treatment effect of Zejula in this
patient population, regardless of biomarker status. These PFS results served
as the primary basis for the US FDA approval for the maintenance treatment of
women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal
cancer who are in complete or partial response to platinum-based chemotherapy.
Overall survival was a secondary endpoint. Updated final overall survival data
was recently shared with the FDA.

 

Hesham Abdullah, SVP, Global Head of Oncology Development, GSK said: "We
believe PARP inhibitors, including Zejula, are important options for the
maintenance treatment of patients with recurrent ovarian cancer, across all
biomarker subgroups, who are in complete or partial response to platinum-based
chemotherapy. We look forward to continuing our ongoing discussions with the
FDA."

The ODAC meeting is scheduled for 22 November 2022. This is not related to the
niraparib indication in the maintenance treatment of adult patients with
advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who
are in a complete or partial response to first-line platinum-based
chemotherapy.

 

About ovarian cancer

Ovarian cancer is the eighth most common cancer in women worldwide. i 
(#_edn1) Despite high response rates to platinum-based chemotherapy in the
front-line setting, approximately 85% of patients will experience disease
recurrence. ii  (#_edn2)   Once the disease recurs, it is rarely curable,
with decreasing time intervals to each subsequent recurrence.

 

About Zejula (niraparib)
Zejula is an oral, once-daily PARP inhibitor currently being evaluated in multiple pivotal trials. GSK is building a robust clinical development programme by assessing activity across multiple tumour types and evaluating several potential combinations of Zejula with other therapeutics. The ongoing development programme includes several combination studies.

 

ZEJULA is indicated:

·      for the maintenance treatment of adult patients with advanced
epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a
complete or partial response to first-line platinum-based chemotherapy

·      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

 

Important Safety Information for ZEJULA

 

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including some
fatal cases, was reported in 15 patients (0.8%) out of 1785 patients treated
with ZEJULA monotherapy in clinical trials. The duration of therapy in
patients who developed secondary MDS/cancer therapy-related AML varied from
0.5 months to 4.9 years. These patients had received prior chemotherapy with
platinum agents and/or other DNA-damaging agents including radiotherapy.
Discontinue ZEJULA if MDS/AML is confirmed.

 

Hematologic adverse reactions (thrombocytopenia, anemia, neutropenia, and/or
pancytopenia) have been reported in patients receiving ZEJULA. The overall
incidence of Grade ≥3 thrombocytopenia, anemia, and neutropenia were
reported, respectively, in 39%, 31%, and 21% of patients receiving ZEJULA in
PRIMA and 29%, 25%, and 20% of patients receiving ZEJULA in NOVA.
Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred,
respectively, in 4%, 2%, and 2% of patients in PRIMA and 3%, 1%, and 2% of
patients in NOVA. In patients who were administered a starting dose of ZEJULA
based on baseline weight or platelet count in PRIMA, Grade ≥3
thrombocytopenia, anemia, and neutropenia were reported, respectively, in 22%,
23%, and 15% of patients receiving ZEJULA. Discontinuation due to
thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 3%,
and 2% of patients. Do not start ZEJULA until patients have recovered from
hematological toxicity caused by prior chemotherapy (≤Grade 1). Monitor
complete blood counts weekly for the first month, monthly for the next 11
months, and periodically thereafter. If hematological toxicities do not
resolve within 28 days following interruption, discontinue ZEJULA, and refer
the patient to a hematologist for further investigations.

 

Hypertension and hypertensive crisis have been reported in patients receiving
ZEJULA. Grade 3-4 hypertension occurred in 6% of patients receiving ZEJULA vs
1% of patients receiving placebo in PRIMA, with no reported discontinuations.
Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of
patients receiving placebo in NOVA, with discontinuation occurring in <1%
of patients. Monitor blood pressure and heart rate at least weekly for the
first two months, then monthly for the first year, and periodically thereafter
during treatment with ZEJULA. Closely monitor patients with cardiovascular
disorders, especially coronary insufficiency, cardiac arrhythmias, and
hypertension. Manage hypertension with antihypertensive medications and
adjustment of the ZEJULA dose if necessary.

 

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of 2,165
patients treated with ZEJULA in clinical trials and has also been described in
postmarketing reports. Monitor all patients for signs and symptoms of PRES,
which include seizure, headache, altered mental status, visual disturbance, or
cortical blindness, with or without associated hypertension. Diagnosis
requires confirmation by brain imaging. If suspected, promptly discontinue
ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA
is unknown.

 

Embryo-fetal toxicity and lactation: Based on its mechanism of action, ZEJULA
can cause fetal harm. Advise females of reproductive potential of the
potential risk to a fetus and to use effective contraception during treatment
and for 6 months after receiving their final dose of ZEJULA. Because of the
potential for serious adverse reactions from ZEJULA in breastfed infants,
advise lactating women to not breastfeed during treatment with ZEJULA and for
1 month after receiving the final dose.

 

Allergic reactions to FD&C Yellow No. 5 (tartrazine): ZEJULA capsules
contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type
reactions (including bronchial asthma) in certain susceptible persons.
Although the overall incidence in the general population is low, it is
frequently seen in patients who also have aspirin hypersensitivity.

 

First-line Maintenance Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of all patients who
received ZEJULA in PRIMA were thrombocytopenia (66%), anemia (64%), nausea
(57%), fatigue (51%), neutropenia (42%), constipation (40%), musculoskeletal
pain (39%), leukopenia (28%), headache (26%), insomnia (25%), vomiting (22%),
dyspnea (22%), decreased appetite (19%), dizziness (19%), cough (18%),
hypertension (18%), AST/ALT elevation (14%), and acute kidney injury (12%).

 

Common lab abnormalities (Grades 1-4) in ≥25% of all patients who received
ZEJULA in PRIMA included: decreased hemoglobin (87%), decreased platelets
(74%), decreased leukocytes (71%), increased glucose (66%), decreased
neutrophils (66%), decreased lymphocytes (51%), increased alkaline phosphatase
(46%), increased creatinine (40%), decreased magnesium (36%), increased AST
(35%) and increased ALT (29%).

 

Maintenance Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received
ZEJULA in NOVA were nausea (74%), thrombocytopenia (61%), fatigue/asthenia
(57%), anemia (50%), constipation (40%), vomiting (34%), neutropenia (30%),
insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis
(23%), rash (21%), hypertension (20%), dyspnea (20%), mucositis/stomatitis
(20%), dizziness (18%), back pain (18%), dyspepsia (18%), leukopenia (17%),
cough (16%), urinary tract infection (13%), anxiety (11%), dry mouth (10%),
AST/ALT elevation (10%), dysgeusia (10%), palpitations (10%).

 

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received
ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet
count (72%), decrease in white blood cell count (66%), decrease in absolute
neutrophil count (53%), increase in AST (36%), and increase in ALT (28%).

 

Please see accompanying US Prescribing Information.
(https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Zejula_Capsules/pdf/ZEJULA-CAPSULES-PI-PIL.PDF)

 

About GSK

GSK is a global biopharma company with a purpose to unite science, technology,
and talent to get ahead of disease together. Find out more at gsk.com/company
(https://www.gsk.com/en-gb/company/) .

 

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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 in
the Company's Annual Report on Form 20-F for 2021, GSK's Q2 Results for 2022
and any impacts of the COVID-19 pandemic.

 

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 i  (#_ednref1) Worldwide Cancer Data. World Cancer Research Fund.
https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data.
Updated January 10, 2022. Accessed July 2022.

 ii  (#_ednref2) Lorusso D, Mancini M, Di Rocco R, Fontanelli R, Raspagliesi
F. The role of secondary surgery in recurrent ovarian cancer [published online
August 5, 2012]. Int J Surg Oncol. 2012. doi:10.1155/2012/613980. Accessed
September 2022.

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