[Federal Register Volume 89, Number 76 (Thursday, April 18, 2024)]
[Notices]
[Pages 27766-27767]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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DATES: Approval of PEPAXTO is withdrawn as of February 23, 2024.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, 
[email protected].

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 https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm. 
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 https://downloads.regulations.gov/FDA-2023-N-3167-0049/attachment_1.pdf. The final decision and other documents pertaining to 
the withdrawal of the NDA for PEPAXTO (NDA 214383) are available at 
https://www.regulations.gov 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