Sedor Pharmaceuticals, LLCSesquient (fosphenytoin sodium) injection

NDA 210864 COMPLETE RESPONSE

Sedor Pharmaceuticals, LLC

Attention: Rick Lampe

Director of Regulatory Affairs & Quality Assurance 1800 East Lancaster Avenue, Suite N

Paoli, PA 19301

Dear Mr. Lampe:

Please refer to your new drug application (NDA) dated and received May 22, 2018, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Sesquient (fosphenytoin sodium) injection, 100 mg and 500 mg phenytoin sodium equivalents/ml.

We acknowledge receipt of your amendment dated June 28, 2019, which constituted a complete response to our March 22, 2019, action letter.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

Product Quality

It is crucial from a safety perspective that the drug product does not contain foreign particles. Information provided to date has not adequately addressed this drug product quality issue.

In a quality information amendment submitted on December 6, 2019, you provided additional study results from ©® regarding particles in the drug product. You concluded that the initial particulate information, obtained in association with the

testing at’ ©, was erroneous and not representative of the drug product due to testing environment conditions. However, there is not sufficient information (e.g., documentation of environmental conditions at) when the ©© testing was performed) to confirm that the initial results from the ®® study are erroneous. Thus, the ®® study report does not conclusively support your contention that the root cause for the particulates observed and characterized by! “in your drug product is laboratory error, and we are unable to disregard the! results.

Characterize the particles observed in the drug product and identify the root cause of their presence (e.g., container closure system, testing method/conditions,

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manufacturing equipment), and provide a Risk Mitigation & Control Plan to mitigate the presence of particulates in your drug product. Provide data demonstrating that the actions taken will prevent reoccurrence of particles in the drug product.

Regulatory

Your original application submitted May 22, 2018, relied on, in part, FDA’s finding of safety and effectiveness for Parke Davis’s NDA 020450 for Cerebyx (fosphenytoin sodium) injection. Our March 22, 2019, complete response (CR) letter included, among other deficiencies, the clinical deficiency “Lack of Adequate Information to Support the Safety of Captisol”. To address this deficiency, the cover letter for your June 28, 2019, resubmission (RS) to our CR letter stated “For additional Captisol safety data, Sedor is also relying on the Agency’s previous findings of safety for the following RLDs: Baxdela™ (NDA 208611), Carnexiv™ (NDA 206030), Vfend® (NDA 021267), and Zulresso™ (NDA 211371)”. Additionally, Field 20 of your June 28, 2019, FDA form 356h identified these NDAs, in addition to Cerebyx NDA 020450, as the basis for your 505(b)(2) (re)submission.

1. Based on our review of your application and your June 28, 2019 RS, we have determined that reliance on Lundbeck Pharmaceuticals’ NDA 206030 for Carnexiv (carbamazepine) solution is needed to justify the safety of the Captisol excipient. We also note that you have a letter of authorization for DMF 14364. Please submit an updated form FDA 356h to reflect reliance on only the Cerebyx and Carnexiv NDAs.

2. Your June 28, 2019, resubmission included Paragraph IV certifications with respect to the following U.S. Patents Nos. listed under Carnexiv NDA 206030: 7,635,773 (the ‘773 patent); 8,410,077 (the ‘077 patent); 9,493,582 (the ‘582 patent); and 9,750,822 (the ‘822 patent). Under 21 CFR 314.52(a), you are required to send notice to the NDA holder and each patent owner for which you submitted a Paragraph IV certification, and 21 CFR 314.52(e) requires that you provide documentation of the date of receipt of such notice. The U.S. Patent and Trademark Office (USPTO) identifies Cydex Pharmaceuticals as the patent owner for the ‘773, ‘077, ‘582, and ‘822 patents. You must send notice of Paragraph IV certification and submit documentation of the date of receipt of such notice by Cydex Pharmaceuticals.

3. On September 23, 2019, you submitted two Domestic Return Receipts for deliveries to Lundbeck Pharmaceuticals, application owner of Carnexiv NDA 206030, as documentation of receipt of Paragraph IV notification. However, the

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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receipts do not indicate the date of delivery (i.e., in Field C of PS Form 3811). Please submit documentation that clearly shows the delivery date to Lundbeck.

PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate, including regulatory issues that could potentially impact the labeling. We encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information’ and Pregnancy and Lactation Labeling Final Rule? websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) - a checklist of important format items from labeling regulations and guidances.

If you revise labeling, use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances. Your response must include updated content of labeling [21 CFR 314.50(I)(1)(i)] in structured product labeling (SPL) format as described at FDA.gov.?

CARTON AND CONTAINER LABELING

Upon resubmission of your application, submit draft carton and container labeling revised as follows: (b) (4)

1 https://www.fda.gov/drugs/laws-acts-and-rules/prescription-drug-labeling-resources 2 https://www.fda.gov/drugs/labeling/pregnancy-and-lactation-labeling-drugs-final-rule 3 http://www.fda.gov/Forlndustry/DataStandards/StructuredProductLabeling/default.htm

3 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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PROPRIETARY NAME

Please refer to correspondence dated, August 27, 2019, which addresses the proposed proprietary name, Sesquient. This name was found acceptable pending approval of the application in the current review cycle. Please resubmit the proposed proprietary name when you respond to the application deficiencies.

SAFETY UPDATE

When you respond to the above deficiencies, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b). The safety update should include data from all nonclinical and clinical studies/trials of the drug under consideration regardless of indication, dosage form, or dose level.

(1) Describe in detail any significant changes or findings in the safety profile. (2) When assembling the sections describing discontinuations due to adverse

events, serious adverse events, and common adverse events, incorporate new safety data as follows:

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e Present new safety data from the studies/clinical trials for the proposed indication using the same format as in the original submission.

e Present tabulations of the new safety data combined with the original application data.

e Include tables that compare frequencies of adverse events in the original application with the retabulated frequencies described in the bullet above.

e For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in Clinical trials.

(3) Present a retabulation of the reasons for premature trial discontinuation by incorporating the drop-outs from the newly completed trials. Describe any new trends or patterns identified.

(4) Provide case report forms and narrative summaries for each patient who died during a Clinical trial or who did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.

(5) Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.

(6) Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).

(7) Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.

(8) Provide English translations of current approved foreign labeling not previously submitted.

OTHER

Within one year after the date of this letter, you are required to resubmit or take other actions available under 21 CFR 314.110. If you do not take one of these actions, we may consider your lack of response a request to withdraw the application under

21 CFR 314.65. You may also request an extension of time in which to resubmit the application.

A resubmission must fully address all the deficiencies listed in this letter and should be clearly marked with "RESUBMISSION" in large font, bolded type at the beginning of the cover letter of the submission. The cover letter should clearly state that you consider this resubmission a complete response to the deficiencies outlined in this letter. A partial U.S. Food and Drug Administration

Silver Spring, MD 20993 www.fda.gov

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response to this letter will not be processed as a resubmission and will not start a new review cycle.

You may request a meeting or teleconference with us to discuss what steps you need to take before the application may be approved. If you wish to have such a meeting, submit your meeting request as described in the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.

The drug product may not be legally marketed until you have been notified in writing that this application is approved.

If you have any questions, contact Heather Bullock, Regulatory Project Manager, at (301) 796-1126 or by email at Heather.Bullock@fda.hhs.gov.

Sincerely, {See appended electronic signature page}

Nick Kozauer, MD

Acting Director

Division of Neurology 2

Office of Neuroscience

Center for Drug Evaluation and Research

U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov

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Signature Page 1 of 1

This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.

NICHOLAS A KOZAUER 12/20/2019 02:35:46 PM

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