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, 20982-20984 [2024-06299]
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20982
Federal Register / Vol. 89, No. 59 / Tuesday, March 26, 2024 / Notices
followup Report to Congress. The
authority for us to collect the
information derives from the
Commissioner of Food and Drugs’
authority provided in section
1003(d)(2)(C) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C.
393(d)(2)(C)).
Protecting the nation’s food and
agriculture supply against intentional
contamination and other emerging
threats is an important responsibility
shared by SLTT governments as well as
private sector partners. FSMA focuses
on ensuring the safety of the U.S. food
supply by shifting the efforts of Federal
regulators from response to prevention
and recognizes the importance of
strengthening existing collaboration
among all stakeholders to achieve
common public health and security
goals. FSMA identifies some key
priorities for working with partners in
areas such as reliance on Federal, State,
and local agencies for inspections;
improving foodborne illness
surveillance; and leveraging and
enhancing State and local food safety
and defense capacities. Section 108 of
FSMA–NAFDS requires HHS and
USDA, in coordination with DHS, to
work together with SLTT to monitor and
measure progress in food defense.
In 2015, the initial NAFDS Report to
Congress detailed the specific Federal
response to food and agriculture defense
goals, objectives, key initiatives, and
activities that HHS, USDA, DHS, and
other stakeholders planned to
accomplish to meet the objectives
outlined in FSMA. The NAFDS charts a
direction for how Federal agencies, in
cooperation with SLTT governments
and private sector partners, protect the
nation’s food supply against intentional
contamination. Not later than 4 years
after the initial NAFDS Report to
Congress (2015), and every 4 years
thereafter (i.e., 2019, 2023, 2027, etc.),
HHS, USDA, and DHS are required to
revise and submit an updated report to
the relevant committees of Congress.
FDA is the agency primarily
responsible for obtaining the
information from Federal and SLTT
partners to complete the NAFDS Report
to Congress. An interagency working
group will conduct the survey and
collect and update the NAFDS as
directed by FSMA, including
developing metrics and measuring
progress for the evaluation process.
The survey of Federal and State
partners will be used to determine what
food defense activities, if any, Federal
and/or SLTT agencies have completed
(or are planning on completing) from
2024 to 2028. Planning for the local,
territorial, and tribal information
collections will commence during this
period of renewal. The survey will
continue to be repeated approximately
every 2 to 4 years, as described in
section 108 of FSMA. The NAFDS
survey is being administered for the
purpose of monitoring progress in food
and agricultural defense by government
agencies.
A purposive sampling strategy is
employed, such that the government
agencies participating in food and
agricultural defense are asked to
respond to the voluntary survey. Food
defense leaders responsible for
conducting food defense activities
during a food emergency for their
jurisdiction are identified and will
receive an emailed invitation to
complete the survey online; they will be
provided with a web link to the survey.
The survey will be conducted
electronically on the FDA.gov web
portal, and results will be analyzed by
the interagency working group.
Description of Respondents:
Respondents to this collection are SLTT
government representatives (survey
respondents) who are food defense
leaders responsible for conducting food
defense activities during a food
emergency for their jurisdictions.
We estimate the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Activity
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average burden
per response
Total hours
SLTT Surveys ............................................................................................
500
1
500
0.33 (20 minutes) .....
165
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
The FDA Office of Partnerships
reviewed the questionnaire and
provided the estimate of time to
complete the survey. The total burden is
based on our previous experiences
conducting surveys. Based on a review
of the information collection since our
last request for OMB approval, we have
made no adjustments to our burden
estimate.
Food and Drug Administration
[Docket No. FDA–2024–N–1056]
[FR Doc. 2024–06316 Filed 3–25–24; 8:45 am]
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
BILLING CODE 4164–01–P
AGENCY:
Dated: March 20, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
ddrumheller on DSK120RN23PROD with NOTICES1
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration,
HHS.
ACTION:
Notice.
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
SUMMARY:
VerDate Sep<11>2014
18:10 Mar 25, 2024
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Frm 00043
Fmt 4703
Sfmt 4703
advanced ovarian cancer for poly (ADPribose) 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–
E:\FR\FM\26MRN1.SGM
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Federal Register / Vol. 89, No. 59 / Tuesday, March 26, 2024 / Notices
796–3137, Kimberly.Lehrfeld@
fda.hhs.gov.
The PARP
inhibitors and their respective
applicants, NDA numbers, and
SUPPLEMENTARY INFORMATION:
Application No.
Drug
Applicant
NDA 209115 ........
Rubraca (rucaparib) Tablets,
equivalent to (EQ) 200 milligrams (mg) base, EQ 250
mg base, and EQ 300 mg
base.
Clovis Oncology, Inc., 5500
Flatiron Pkwy., Boulder,
CO 80301.
NDA 208558 ........
Lynparza (197laparib) Tablets, 100 mg and 150 mg.
AstraZeneca Pharmaceuticals
LP, 1800 Concord Pike,
Wilmington, DE 19803.
NDA 208447 ........
Zejula (niraparib) Capsules,
EQ 100 mg base.
GlaxoSmithKline, LLC, 2929
Walnut St., Suite 1700,
Philadelphia, PA 19104.
I. RUBRACA (Rucaparib) Tablets
ddrumheller on DSK120RN23PROD with NOTICES1
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
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 ClinicalTrials.gov web page at https://
clinicaltrials.gov/ct2/show/NCT02855944.
VerDate Sep<11>2014
18:10 Mar 25, 2024
Jkt 262001
for the treatment of adult patients with a deleterious BRCA
mutation (germline and/or somatic)-associated epithelial
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.
for the treatment of adult patients with deleterious or suspected deleterious 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.
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 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
6 months after response to the last platinum-based
chemotherapy.
Select patients for therapy based on an FDA-approved
companion diagnostic device for ZEJULA.
B. Withdrawal of Approval of Indication
for RUBRACA Tablets
Therefore, under § 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
Frm 00044
Fmt 4703
indications being withdrawn are
included in the following table.
Indication being withdrawn
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
§ 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
§ 314.150(d) and waiving its
opportunity for a hearing.
PO 00000
20983
Sfmt 4703
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
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 ClinicalTrials.gov web page at https://
clinicaltrials.gov/ct2/show/NCT02282020.
E:\FR\FM\26MRN1.SGM
26MRN1
20984
Federal Register / Vol. 89, No. 59 / Tuesday, March 26, 2024 / Notices
voluntarily permit FDA to withdraw
approval of the indication for the
treatment of adult patients with
deleterious germline BRCA mutationassociated advanced ovarian cancer who
have been treated with three or more
chemotherapies, pursuant to
§ 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 § 314.150(d) and waiving its
opportunity for a hearing.
B. Withdrawal of Approval of Indication
for Lynparza Tablets
Therefore, under § 314.150(d),
approval of the indication for the
treatment of adult patients with
deleterious germline BRCA mutationassociated 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.
ddrumheller on DSK120RN23PROD with NOTICES1
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
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
VerDate Sep<11>2014
18:10 Mar 25, 2024
Jkt 262001
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 § 314.150(d) and
waiving its opportunity for a hearing.
B. Withdrawal of Approval of Indication
for Zejula Capsules
Therefore, under § 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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2024–N–1179]
Oncologic Drugs Advisory Committee;
Notice of Meeting; Establishment of a
Public Docket; Request for
Comments—Use of Minimal Residual
Disease as an Endpoint in Multiple
Myeloma Clinical Trials
AGENCY:
Food and Drug Administration,
recommendations to FDA on regulatory
issues. The meeting will be open to the
public. FDA is establishing a docket for
public comment on this document.
DATES: The meeting will be held on
April 12, 2024, from 9 a.m. to 4 p.m.
Eastern Time.
ADDRESSES: FDA and invited
participants may attend the meeting at
FDA White Oak Campus, 10903 New
Hampshire Ave., Bldg. 31 Conference
Center, the Great Room (Rm. 1503),
Silver Spring, MD 20993–0002. The
public will have the option to
participate via an online
teleconferencing and/or video
conferencing platform, and the advisory
committee meeting will be heard,
viewed, captioned, and recorded
through an online teleconferencing and/
or video conferencing platform.
Answers to commonly asked
questions about FDA advisory
committee meetings may be accessed at:
https://www.fda.gov/Advisory
Committees/AboutAdvisoryCommittees/
ucm408555.htm.
FDA is establishing a docket for
public comment on this meeting. The
docket number is FDA–2024–N–1179.
The docket will close on April 11, 2024.
Please note that late, untimely filed
comments will not be considered. The
https://www.regulations.gov electronic
filing system will accept comments
until 11:59 p.m. Eastern Time at the end
April 11, 2024. Comments received by
mail/hand delivery/courier (for written/
paper submissions) will be considered
timely if they are received on or before
that date.
Comments received on or before April
3, 2024, will be provided to the
Committee. Comments received after
that date will be taken into
consideration by FDA. In the event that
the meeting is cancelled, FDA will
continue to evaluate any relevant
applications or information, and
consider any comments submitted to the
docket, as appropriate.
You may submit comments as
follows:
HHS.
Electronic Submissions
Notice; establishment of a
public docket; request for comments.
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
ACTION:
The Food and Drug
Administration (FDA) announces a
forthcoming public advisory committee
meeting of the Oncologic Drugs
Advisory Committee (the Committee).
The general function of the Committee
is to provide advice and
SUMMARY:
on the NIH National Library of Medicine’s
ClinicalTrials.gov web page at https://clinicaltrials.
gov/ct2/show/NCT02354586.
PO 00000
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E:\FR\FM\26MRN1.SGM
26MRN1
]]>Agencies
[Federal Register Volume 89, Number 59 (Tuesday, March 26, 2024)]
[Notices]
[Pages 20982-20984]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-06299]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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, [email protected].
SUPPLEMENTARY INFORMATION: The PARP inhibitors and their respective
applicants, NDA numbers, and indications being withdrawn are included
in the following table.
----------------------------------------------------------------------------------------------------------------
Application No. Drug Applicant Indication being withdrawn
----------------------------------------------------------------------------------------------------------------
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:
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.
Select patients for therapy
based on an FDA-approved
companion diagnostic
device for ZEJULA.
----------------------------------------------------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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
ClinicalTrials.gov web page at https://clinicaltrials.gov/ct2/show/NCT02855944.
---------------------------------------------------------------------------
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 ClinicalTrials.gov web page at
https://clinicaltrials.gov/ct2/show/NCT02282020.
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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 ClinicalTrials.gov web page at
https://clinicaltrials.gov/ct2/show/NCT02354586.
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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
