Notice2023-18320
Notice of Opportunity for Public Comment on Proposal To Withdraw Approval of New Drug Application for PEPAXTO, Equivalent to 20 Milligrams Base per Vial
Primary source
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Published
August 25, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA, the Agency) is proposing to withdraw approval of PEPAXTO (melphalan flufenamide) for injection, equivalent to (EQ) 20 milligrams (mg) BASE/VIAL, once every 28 days, new drug application (NDA) 214383, held by Oncopeptides AB (Oncopeptides). This notice is intended to provide an opportunity for public comment on CDER's proposed withdrawal of PEPAXTO, in accordance with the expedited withdrawal of approval procedures described in the Federal Food, Drug and Cosmetic Act (FD&C Act).
Full Text
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<title>Federal Register, Volume 88 Issue 164 (Friday, August 25, 2023)</title>
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[Federal Register Volume 88, Number 164 (Friday, August 25, 2023)]
[Notices]
[Pages 58282-58284]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-18320]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-3167]
Notice of Opportunity for Public Comment on Proposal To Withdraw
Approval of New Drug Application for PEPAXTO, Equivalent to 20
Milligrams Base per Vial
AGENCY: Center for Drug Evaluation and Research, Food and Drug
Administration, HHS.
[[Page 58283]]
ACTION: Notice of opportunity for public comment.
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SUMMARY: The Center for Drug Evaluation and Research (CDER) of the Food
and Drug Administration (FDA, the Agency) is proposing to withdraw
approval of PEPAXTO (melphalan flufenamide) for injection, equivalent
to (EQ) 20 milligrams (mg) BASE/VIAL, once every 28 days, new drug
application (NDA) 214383, held by Oncopeptides AB (Oncopeptides). This
notice is intended to provide an opportunity for public comment on
CDER's proposed withdrawal of PEPAXTO, in accordance with the expedited
withdrawal of approval procedures described in the Federal Food, Drug
and Cosmetic Act (FD&C Act).
DATES: Either electronic or written comments on this proposal to
withdraw PEPAXTO must be submitted by September 25, 2023.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. The <a href="https://www.regulations.gov">https://www.regulations.gov</a> electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of September 25, 2023. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are received on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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 third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2023-N-3167 for ``Notice of Opportunity for Public Comment on
Proposal To Withdraw Approval of New Drug Application for PEPAXTO,
Equivalent to 20 Milligrams Base per Vial.'' Received comments, those
filed in a timely manner (see ADDRESSES), will be placed in the docket
and, except for those submitted as ``Confidential Submissions,''
publicly viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Anuj Shah, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 6224, Silver Spring, MD 20993-0002, 301-796-2246.
SUPPLEMENTARY INFORMATION:
I. Background
FDA approved NDA 214383 for PEPAXTO on February 26, 2021, under the
accelerated approval pathway (section 506(c) of the FD&C Act (21 U.S.C.
356(c)) and 21 CFR part 314, subpart H) for use in combination with
dexamethasone for the treatment of adult patients with relapsed or
refractory multiple myeloma who have received at least four prior lines
of therapy and whose disease is refractory to at least one proteasome
inhibitor, one immunomodulatory drug, and one CD38-directed monoclonal
antibody (triple class refractory).\1\
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\1\ Most patients in the United States with relapsed disease
will have been exposed to lenalidomide (an immunomodulatory agent),
a proteasome inhibitor, corticosteroids, and an anti-CD38 monoclonal
antibody after one or two lines of treatment, and retreatment with
previously used agents or agents in the same class of drug can be
effective.
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NDA 214383 relied on evidence from Trial OP-106 (<a href="http://ClinicalTrials.gov">ClinicalTrials.gov</a>
NCT number, NCT02963493), also known as HORIZON, a single-arm, open-
label, phase 2 multicenter clinical trial that enrolled patients with
relapsed or refractory multiple myeloma and who received at least two
lines of prior therapy including an immunomodulatory drug and a
proteasome inhibitor. The primary endpoint was overall response rate
(ORR),\2\ as assessed by the investigator.
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\2\ ORR was defined as the proportion of patients with a best
confirmed response of stringent complete response, complete
response, very good partial response, or partial response according
to the International Myeloma Working Group Uniform Response
Criteria.
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At the time of approval under the accelerated approval pathway, the
applicant was required to conduct an appropriate post-approval study to
verify and describe the clinical benefit of PEPAXTO.\3\ CDER has
determined
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withdrawal of approval is warranted because the required post-approval
confirmatory trial failed to verify clinical benefit and because
available evidence demonstrates PEPAXTO is not shown to be safe or
effective under its conditions of use. The Oncologic Drugs Advisory
Committee (ODAC) convened on September 22, 2022, to discuss issues
related to this proposed withdrawal. The ODAC voted 14 to 2 that the
benefit-risk profile of melphalan flufenamide was not favorable for the
currently indicated patient population. For additional background,
please refer to CDER's letter to Oncopeptides Re: Section 506(c)(3)(B)
Notice of Proposed Withdrawal of Approval; PEPAXTO (melphalan
flufenamide) for injection; NDA 214383 (``Notice to Oncopeptides of
Proposed Withdrawal of PEPAXTO'') and CDER's Proposed Withdrawal of
PEPAXTO Decisional Memorandum, available at Docket No. FDA-2023-N-3167,
<a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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\3\ Section 506(c)(2)(A)(i) of the FD&C Act (as renumbered by
the Consolidated Appropriations Act of 2023 (Pub. L. 117-328); see
also 21 CFR 314.510.
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II. Legal Standard for Withdrawal of Approval
Section 506(c) of the FD&C Act, as amended most recently by the
Consolidated Appropriations Act of 2023 (Pub. L. 117-328), describes
the accelerated approval of new drug applications and the procedures
and authority governing expedited withdrawal of approval. FDA has the
legal authority to use the expedited procedures to withdraw approval of
a product that has received accelerated approval if, among other
reasons, ``a study required to verify and describe the predicted effect
on irreversible morbidity or mortality or other clinical benefit of the
product fails to verify and describe such effect or benefit'' (section
506(c)(3)(A)(ii) of the FD&C Act) or ``other evidence demonstrates that
the product is not shown to be safe or effective under the conditions
of use.'' (section 506(c)(3)(A)(iii) of the FD&C Act.)
III. Explanation for the Proposed Withdrawal
CDER proposes to withdraw approval of PEPAXTO because the required
confirmatory study, Trial OP-103, also known as OCEAN, failed to verify
clinical benefit and because available evidence demonstrates PEPAXTO is
not shown to be safe or effective under its conditions of use. More
specifically, the results failed to show that PEPAXTO had a significant
effect on the primary endpoint of progression-free survival.
Furthermore, the observed median overall survival was 5.3 months
shorter in the PEPAXTO arm compared to the control arm. After
considering all the available data and the discussion at the ODAC held
in September 2022, CDER recommends withdrawing the accelerated approval
for PEPAXTO. Please refer to CDER's ``Notice to Oncopeptides of
Proposed Withdrawal of PEPAXTO'' and ``Proposed Withdrawal of PEPAXTO
Decisional Memorandum'' for additional explanation.
IV. Opportunity for Public Comment on CDER's Proposal To Withdraw
Approval of PEPAXTO
In accordance with the expedited withdrawal of approval procedures
described in section 506(c)(3)(B)(ii) and (iii) of the FD&C Act, CDER
is providing an opportunity for public comment on its proposal to
withdraw approval of NDA 214383 (PEPAXTO) through the issuance of a
Federal Register Notice. FDA will consider any such public comments it
receives in making its decision on CDER's proposal to withdraw approval
of NDA 214383 (PEPAXTO) and make available on its website and in the
public docket a summary of such comments and FDA's response to them.
Dated: August 21, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-18320 Filed 8-24-23; 8:45 am]
BILLING CODE 4164-01-P
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</html>Indexed from Federal Register on August 25, 2023.
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