Notice2024-06299
Clovis Oncology, Inc., AstraZeneca Pharmaceuticals LP, and GlaxoSmithKline LLC; Withdrawal of Approval of the Indications for Advanced Ovarian Cancer for Poly (ADP-Ribose) Polymerase Inhibitors RUBRACA (Rucaparib) Tablets, LYNPARZA (Olaparib) Tablets, and ZEJULA (Niraparib) Capsules
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Published
March 26, 2024
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing that it is withdrawing approval of the indications for the treatment of adult patients with advanced ovarian cancer for poly (ADP-ribose) polymerase (PARP) inhibitors under three new drug applications (NDAs) from multiple applicants. The applicants Clovis Oncology, Inc. (Clovis), AstraZeneca Pharmaceuticals LP (AZ), and GlaxoSmithKline, LLC (GSK) have each voluntarily requested that the Agency withdraw approval of the indications for the treatment of adult patients with advanced ovarian cancer for their respective PARP inhibitors and waived their opportunities for hearings. Applicant and indication details are further discussed in SUPPLEMENTARY INFORMATION.
Full Text
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<title>Federal Register, Volume 89 Issue 59 (Tuesday, March 26, 2024)</title>
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[Federal Register Volume 89, Number 59 (Tuesday, March 26, 2024)]
[Notices]
[Pages 20982-20984]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-06299]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2024-N-1056]
Clovis Oncology, Inc., AstraZeneca Pharmaceuticals LP, and
GlaxoSmithKline LLC; Withdrawal of Approval of the Indications for
Advanced Ovarian Cancer for Poly (ADP-Ribose) Polymerase Inhibitors
RUBRACA (Rucaparib) Tablets, LYNPARZA (Olaparib) Tablets, and ZEJULA
(Niraparib) Capsules
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
that it is withdrawing approval of the indications for the treatment of
adult patients with advanced ovarian cancer for poly (ADP-ribose)
polymerase (PARP) inhibitors under three new drug applications (NDAs)
from multiple applicants. The applicants Clovis Oncology, Inc.
(Clovis), AstraZeneca Pharmaceuticals LP (AZ), and GlaxoSmithKline, LLC
(GSK) have each voluntarily requested that the Agency withdraw approval
of the indications for the treatment of adult patients with advanced
ovarian cancer for their respective PARP inhibitors and waived their
opportunities for hearings. Applicant and indication details are
further discussed in SUPPLEMENTARY INFORMATION.
DATES: Approval is withdrawn as of March 26, 2024.
FOR FURTHER INFORMATION CONTACT: Kimberly Lehrfeld, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6226, Silver Spring, MD 20993-0002, 301-
[[Page 20983]]
796-3137, <a href="/cdn-cgi/l/email-protection#fdb694909f988f9184d3b198958f9b989199bd9b999cd395958ed39a928b"><span class="__cf_email__" data-cfemail="064d6f6b6463746a7f284a636e7460636a6246606267286e6e7528616970">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION: The PARP inhibitors and their respective
applicants, NDA numbers, and indications being withdrawn are included
in the following table.
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Application No. Drug Applicant Indication being withdrawn
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NDA 209115......................... Rubraca (rucaparib) Clovis Oncology, Inc., for the treatment of adult
Tablets, equivalent 5500 Flatiron Pkwy., patients with a
to (EQ) 200 Boulder, CO 80301. deleterious BRCA mutation
milligrams (mg) base, (germline and/or somatic)-
EQ 250 mg base, and associated epithelial
EQ 300 mg base. ovarian, fallopian tube,
or primary peritoneal
cancer who have been
treated with two or more
chemotherapies. Select
patients for therapy based
on an FDA-approved
companion diagnostic for
RUBRACA.
NDA 208558......................... Lynparza (197laparib) AstraZeneca for the treatment of adult
Tablets, 100 mg and Pharmaceuticals LP, patients with deleterious
150 mg. 1800 Concord Pike, or suspected deleterious
Wilmington, DE 19803. germline BRCA-mutated
advanced ovarian cancer
who have been treated with
three or more prior lines
of chemotherapy. Select
patients for therapy based
on an FDA-approved
companion diagnostic for
LYNPARZA.
NDA 208447......................... Zejula (niraparib) GlaxoSmithKline, LLC, for the treatment of adult
Capsules, EQ 100 mg 2929 Walnut St., patients with advanced
base. Suite 1700, ovarian, fallopian tube,
Philadelphia, PA or primary peritoneal
19104. cancer 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:
<bullet> a deleterious or
suspected deleterious BRCA
mutation, or
<bullet> genomic
instability and who have
progressed more than 6
months after response to
the last platinum-based
chemotherapy.
Select patients for therapy
based on an FDA-approved
companion diagnostic
device for ZEJULA.
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I. RUBRACA (Rucaparib) Tablets
A. Application Background
On December 19, 2016, FDA approved NDA 209115 for RUBRACA
(rucaparib) Tablets, EQ 200 mg base, EQ 250 mg base, and EQ 300 mg
base, for the treatment of adult patients with advanced ovarian cancer
(see table for full indication \1\). On May 4, 2022, FDA met with
Clovis to discuss the final results from the clinical trial entitled
``ARIEL4 (Assessment of Rucaparib in Ovarian CancEr TriaL): A Phase 3
Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in
Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian,
Fallopian Tube, or Primary Peritoneal Cancer.'' \2\ The results
indicated that patients in the intent-to-treat population who were
taking rucaparib potentially had a shorter overall survival (OS) than
patients not on rucaparib. At that meeting FDA conveyed that these
results constituted a serious risk for patients receiving treatment
with rucaparib. On May 10, 2022, the Agency asked Clovis, in writing,
to voluntarily permit FDA to withdraw approval of the indication for
the treatment of adult patients with deleterious BRCA mutation-
associated epithelial ovarian, fallopian tube or primary peritoneal
cancer who have been treated with two or more chemotherapies, pursuant
to Sec. 314.150(d) (21 CFR 314.150(d)) and waive its opportunity for a
hearing. On June 1, 2022, Clovis submitted a letter requesting
withdrawal of approval of this indication for RUBRACA (rucaparib)
Tablets pursuant to Sec. 314.150(d) and waiving its opportunity for a
hearing.
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\1\ The initially approved indication was ``as monotherapy for
the treatment of patients with deleterious BRCA mutation (germline
and/or somatic)-associated advanced ovarian cancers [emphasis added]
who have been treated with two or more chemotherapies. Select
patients for therapy based on an FDA-approved companion diagnostic
for RUBRACA.'' On April 6, 2018, the Agency approved a revised
indication that, among other things, clarified the indication by
listing the following specific advanced ovarian cancers in the
indication: epithelial ovarian, fallopian tube, and primary
peritoneal cancer.
\2\ The study, under its abbreviated title ``ARIEL4: A Study of
Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube,
or Primary Peritoneal Cancer Patients,'' is available on the
National Institutes of Health (NIH) National Library of Medicine's
<a href="http://ClinicalTrials.gov">ClinicalTrials.gov</a> web page at <a href="https://clinicaltrials.gov/ct2/show/NCT02855944">https://clinicaltrials.gov/ct2/show/NCT02855944</a>.
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B. Withdrawal of Approval of Indication for RUBRACA Tablets
Therefore, under Sec. 314.150(d), approval of the indication for
the treatment of adult patients with deleterious BRCA mutation-
associated epithelial ovarian, fallopian tube or primary peritoneal
cancer who have been treated with two or more chemotherapies for
RUBRACA (rucaparib) Tablets is withdrawn as of March 26, 2024.
Withdrawal of approval of this indication does not affect any other
approved indication for RUBRACA (rucaparib) Tablets.
II. LYNPARZA (Olaparib) Tablets
A. Application Background
On August 17, 2017, FDA approved NDA 208558 for LYNPARZA (olaparib)
Tablets, 100 mg and 150 mg, for the treatment of adult patients with
advanced ovarian cancer (see table for full indication). On July 14,
2022, FDA met with AZ to discuss the final OS results from the clinical
trial entitled ``A Phase III, Open Label, Randomised, Controlled,
Multi-centre Study to Assess the Efficacy and Safety of Olaparib
Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the
Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients
Carrying Germline BRCA1/2 Mutations'' (SOLO3).\3\ The results indicated
that patients who were taking olaparib potentially had a shorter OS
than patients not on olaparib, particularly in the subgroup analysis of
patients who had received three or more lines of chemotherapy. On July
26, 2022, the Agency asked AZ, in writing, to
[[Page 20984]]
voluntarily permit FDA to withdraw approval of the indication for the
treatment of adult patients with deleterious germline BRCA mutation-
associated advanced ovarian cancer who have been treated with three or
more chemotherapies, pursuant to Sec. 314.150(d) and waive its
opportunity for a hearing for NDA 208558. On August 19, 2022, AZ
submitted a letter requesting withdrawal of approval of this indication
for LYNPARZA (olaparib) Tablets (NDA 208558) pursuant to Sec.
314.150(d) and waiving its opportunity for a hearing.
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\3\ The study, under its abbreviated title ``Olaparib Treatment
in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA)
Mutated Ovarian Cancer Patients Who Have Progressed at Least 6
Months After Last Platinum Treatment and Have Received at Least 2
Prior Platinum Treatments (SOLO3),'' is available on the NIH
National Library of Medicine's <a href="http://ClinicalTrials.gov">ClinicalTrials.gov</a> web page at
<a href="https://clinicaltrials.gov/ct2/show/NCT02282020">https://clinicaltrials.gov/ct2/show/NCT02282020</a>.
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B. Withdrawal of Approval of Indication for Lynparza Tablets
Therefore, under Sec. 314.150(d), approval of the indication for
the treatment of adult patients with deleterious germline BRCA
mutation-associated advanced ovarian cancer who have been treated with
three or more chemotherapies for LYNPARZA (olaparib) Tablets is
withdrawn as of March 26, 2024. Withdrawal of approval of this
indication does not affect any other approved indication for LYNPARZA
(200laparib) Tablets.
III. ZEJULA (Niraparib) Capsules
A. Application Background
On October 23, 2019, FDA approved NDA 208447 for ZEJULA (niraparib)
Capsules, EQ 100 mg base, for the treatment of adult patients with
advanced ovarian cancer (see table for full indication). On August 4,
2022, FDA met with GSK to discuss the status of the ZEJULA (niraparib)
Capsules indication for the treatment of adult patients with advanced
ovarian cancer. FDA requested that GSK voluntarily permit FDA to
withdraw approval of this indication because the results from
randomized trials of rucaparib and olaparib in similar treatment
settings showed OS may be reduced in patients receiving PARP
inhibitors. FDA stated that these results from two independent trials
were concerning and suggested a class-wide effect for PARP inhibitors.
In correspondence dated August 24, 2022, GSK acknowledged that because
of the uncontrolled nature of the trial entitled ``A Phase 2, Open-
Label, Single-Arm Study to Evaluate the Safety and Efficacy of
Niraparib in Patients With Advanced, Relapsed, High-Grade Serous
Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who
Have Received Three or Four Previous Chemotherapy Regimens'' \4\ on
which approval of this indication was based, it would be difficult to
demonstrate that niraparib does not impact survival in this treatment
setting. Therefore, GSK agreed to voluntarily withdraw the advanced
ovarian cancer indication. On September 7, 2022, GSK submitted a letter
requesting withdrawal of approval of this indication for ZEJULA
(niraparib) Capsules pursuant to Sec. 314.150(d) and waiving its
opportunity for a hearing.
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\4\ The study, under its abbreviated title ``A Study of
Niraparib in Patients With Ovarian Cancer Who Have Received Three or
Four Previous Chemotherapy Regimens (QUADRA),'' is available on the
NIH National Library of Medicine's <a href="http://ClinicalTrials.gov">ClinicalTrials.gov</a> web page at
<a href="https://clinicaltrials.gov/ct2/show/NCT02354586">https://clinicaltrials.gov/ct2/show/NCT02354586</a>.
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B. Withdrawal of Approval of Indication for Zejula Capsules
Therefore, under Sec. 314.150(d), approval of the indication for
the treatment of adult patients with advanced ovarian, fallopian tube,
or primary peritoneal cancer who have been treated with three or more
prior chemotherapy regimens and whose cancer is associated with HRD
positive status defined by either a deleterious or suspected
deleterious BRCA mutation or genomic instability and who have
progressed more than 6 months after response to the last platinum-based
chemotherapy for ZEJULA (niraparib) Capsules is withdrawn as of March
26, 2024. Withdrawal of approval of this indication does not affect any
other approved indication for ZEJULA (niraparib) Capsules.
Dated: March 19, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-06299 Filed 3-25-24; 8:45 am]
BILLING CODE 4164-01-P
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