Notice2024-08274
Final Decision on Withdrawal of PEPAXTO (melphalan flufenamide) Following Appeal of the Proposal To Withdraw Approval; Availability of Final Decision
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Published
April 18, 2024
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing the availability of the final decision withdrawing approval of PEPAXTO (melphalan flufenamide), for injection, equivalent to 20 milligrams (mg) base/vial, once every 28 days, under the new drug application (NDA) 214383, held by Oncopeptides AB (Oncopeptides). The Commissioner of Food and Drugs' (the Commissioner's) designee issued the decision, and a summary of responses to public comments. The Commissioner's designee issued this decision following the Center for Drug Evaluation and Research's (CDER) proposal to withdraw approval of PEPAXTO, Oncopeptides' appeal of the proposed withdrawal, a meeting between the designee and Oncopeptides, a public comment period on the proposed withdrawal, and an advisory committee that CDER convened and consulted on issues related to the proposed withdrawal.
Full Text
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<title>Federal Register, Volume 89 Issue 76 (Thursday, April 18, 2024)</title>
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[Federal Register Volume 89, Number 76 (Thursday, April 18, 2024)]
[Notices]
[Pages 27766-27767]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2024-08274]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2023-N-3167]
Final Decision on Withdrawal of PEPAXTO (melphalan flufenamide)
Following Appeal of the Proposal To Withdraw Approval; Availability of
Final Decision
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of the final decision withdrawing approval of PEPAXTO
(melphalan flufenamide), for injection, equivalent to 20 milligrams
(mg) base/vial, once every 28 days, under the new drug application
(NDA) 214383, held by Oncopeptides AB (Oncopeptides). The Commissioner
of Food and Drugs' (the Commissioner's) designee issued the decision,
and a summary of responses to public comments. The Commissioner's
designee issued this decision following the Center for Drug Evaluation
and Research's (CDER) proposal to withdraw approval of PEPAXTO,
Oncopeptides' appeal of the proposed withdrawal, a meeting between the
designee and Oncopeptides, a public comment period on the proposed
withdrawal, and an advisory committee that CDER convened and consulted
on issues related to the proposed withdrawal.
DATES: Approval of PEPAXTO is withdrawn as of February 23, 2024.
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, 301-796-3600,
<a href="/cdn-cgi/l/email-protection#34755a415e1a675c555c745250551a5c5c471a535b42"><span class="__cf_email__" data-cfemail="82c3ecf7e8acd1eae3eac2e4e6e3aceaeaf1ace5edf4">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
On February 26, 2021, FDA approved NDA 214383 for PEPAXTO
(melphalan flufenamide) for injection, 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 agent, and one CD38-directed monoclonal
antibody (triple class refractory). FDA approved PEPAXTO under the
accelerated approval pathway, pursuant to section 506(c) of the Federal
Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 356(c)) and 21 CFR
314.510, based on evidence of the drug's effect on an intermediate
clinical endpoint that was considered reasonably likely to predict the
drug's clinical benefit.
As a condition of PEPAXTO's approval, the sponsor was required to
complete a postapproval confirmatory trial to verify and describe the
clinical benefit of PEPAXTO. The postapproval confirmatory trial, Trial
OP-103, failed to meet the primary endpoint of progression-free
survival superiority compared to the control arm and demonstrated a
lower median overall survival compared to the control arm.
On September 22, 2022, an Oncologic Drugs Advisory Committee (ODAC)
meeting was held to discuss the results of Trial OP-103. The committee
discussed issues that were ultimately related to the withdrawal,
including the progression-free survival results, overall survival
results, dosing concerns, subpopulation considerations, and the
benefit-risk profile of PEPAXTO for the patient population for which
the drug was indicated. The ODAC voted 14 to 2 that the benefit-risk
profile of PEPAXTO was not favorable for the patient population for
which the drug was indicated.
On July 7, 2023, pursuant to the expedited withdrawal procedures
under section 506(c)(3)(B) of the FD&C Act, CDER provided due notice to
Oncopeptides of the proposal to withdraw approval of PEPAXTO on two
independent grounds: (1) the postapproval confirmatory trial failed to
verify clinical benefit and (2) the evidence demonstrates that the drug
is not shown to be safe or effective under its conditions of use.
CDER's notice provided Oncopeptides with an explanation for the
proposed withdrawal, and advised Oncopeptides that it had the
opportunity for a written appeal to and a meeting with the
Commissioner, or the Commissioner's designee, regarding CDER's
proposal.
On July 26, 2023, Oncopeptides submitted a letter indicating an
intent to appeal the proposal to withdraw approval and requesting a
meeting with the FDA Commissioner or the Commissioner's designee with
respect to the proposed withdrawal of approval.
On August 4, 2023, Oncopeptides submitted its written appeal of
CDER's proposal to withdraw approval of PEPAXTO. On August 9, 2023, Dr.
Peter Marks, Director, Center for Biologics Evaluation and Research,
notified the parties that the Commissioner had designated him to serve
as the Commissioner's designee under section 506(c)(3)(B) of the FD&C
Act. CDER submitted a response to Oncopeptides' written appeal on
September 8, 2023, and Oncopeptides replied to CDER's response on
September 19, 2023. On September 29, 2023, CDER submitted a response to
Oncopeptides' September 19, 2023, correspondence. On October 2, 2023,
Oncopeptides and CDER met with the Commissioner's designee, and both
Oncopeptides and CDER submitted additional information requested by the
designee after the meeting.
Consistent with the expedited withdrawal procedures under section
506(c)(3)(B) of the FD&C Act, CDER issued on August 25, 2023, a Notice
of Opportunity for Public Comment on its proposal to withdraw PEPAXTO;
the comment period remained open until September 25, 2023. The
September 22, 2022, ODAC meeting had previously discussed and provided
recommendations on issues with respect to the withdrawal of PEPAXTO.
On February 23, 2024, after reviewing the record and considering
the arguments on appeal, the Commissioner's designee issued a final
decision finding the grounds for withdrawal were met and that
withdrawal was appropriate, withdrawing approval of PEPAXTO.
FDA has thus withdrawn approval of the following NDA:
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Application No. Drug Holder/Sponsor
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NDA 214383................. Pepaxto (melphalan Oncopeptides AB.
flufenamide) for
Injection.
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[[Page 27767]]
Withdrawal of approval of PEPAXTO (NDA 214383) was effective
February 23, 2024; the withdrawal includes all amendments and
supplements to the application. As discussed in the decision of the
Commissioner's designee, FDA has withdrawn approval of the PEPAXTO NDA
for reasons of safety or effectiveness.
Section 505(j)(7) of the FD&C Act (21 U.S.C. 355(j)(7)) requires
FDA to publish a list of all approved drugs. FDA publishes this list as
part of the ``Approved Drug Products With Therapeutic Equivalence
Evaluations,'' which is known generally as the ``Orange Book,''
available at <a href="https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm">https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm</a>.
Pursuant to section 505(j)(7)(C) of the FD&C Act, drugs are removed
from the list if FDA determines that the listed drug has been withdrawn
from sale for reasons of safety or effectiveness. Accordingly, the
Agency has removed the application for PEPAXTO from the list of drug
products published in the Orange Book. FDA will not accept or approve
ANDAs that reference PEPAXTO.
II. Electronic Access
Persons with access to the internet may obtain the final decision
at <a href="https://downloads.regulations.gov/FDA-2023-N-3167-0049/attachment_1.pdf">https://downloads.regulations.gov/FDA-2023-N-3167-0049/attachment_1.pdf</a>. The final decision and other documents pertaining to
the withdrawal of the NDA for PEPAXTO (NDA 214383) are available at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> under the docket number found in brackets
in the heading of this document.
Dated: April 15, 2024.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2024-08274 Filed 4-17-24; 8:45 am]
BILLING CODE 4164-01-P
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