89 FR 76 pgs. 27766-27767 - Final Decision on Withdrawal of PEPAXTO (melphalan flufenamide) Following Appeal of the Proposal To Withdraw Approval; Availability of Final Decision
Type: NOTICEVolume: 89Number: 76Pages: 27766 - 27767
Pages: 27766, 27767Docket number: [Docket No. FDA-2023-N-3167]
FR document: [FR Doc. 2024-08274 Filed 4-17-24; 8:45 am]
Agency: Health and Human Services Department
Sub Agency: Food and Drug Administration
Official PDF Version: PDF Version
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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.
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Approval of PEPAXTO is withdrawn as of February 23, 2024.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, Anuj.Shah@fda.hhs.gov.
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:
| Application No. | Drug | Holder/Sponsor |
|---|---|---|
| NDA 214383 | Pepaxto (melphalan flufenamide) for Injection | Oncopeptides AB. |
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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]
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