Ferring Pharmaceuticals Inc.Nocdurna (desmopressin) Orally Disintegrating Tablets, 25 mcg and 50 mcg

NDA 022517

Food and Drug Administration Silver Spring MD 20993

COMPLETE RESPONSE

Ferring Pharmaceuticals Inc.

Attention: Brenda Marczi, Pharm.D. Vice President, U.S. Regulatory Affairs 100 Interpace Parkway

Parsippany, NJ 07054

Dear Dr. Marczi:

Please refer to your New Drug Application (NDA) dated June 19, 2009, received June 22, 2009, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for Nocdurna (desmopressin) Orally Disintegrating Tablets, 25 mcg and 50 mcg.

We acknowledge receipt of your amendments dated August 17 (2) and 25, September 18 and 30, October 20, November 3, December 22, 2009, January 14, March 11, April 15 and 19, 2010, May 24 and October 14, 2011, July 30 and 31, October 12 and 16, 2012, January 9, July 17, 2013, July 31, September 9 and 23, and November 18, 2014.

The July 31, 2014, submission constituted a complete response to our January 30, 2013, 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.

CLINICAL/STATISTICAL

We have reviewed the information submitted in your July 31, 2014, Complete Response to our January 30, 2013, action letter. On January 12, 2015, the efficacy and safety findings from the Nocdurna clinical development program were discussed publicly at a meeting of the Endocrinologic and Metabolic Drugs Advisory Committee. After considering the information in your submission and discussions at the advisory committee meeting we have determined that you have provided insufficient evidence to conclude that the effect of Nocdurna relative to placebo on the number of nocturnal voids in adults with nocturia due to nocturnal polyuria is clinically meaningful and outweighs the risks of hyponatremia associated with use of the drug.

To address this deficiency you will need to conduct a trial to demonstrate that Nocdurna provides a meaningful clinical benefit that is associated with the reduction in number of nocturnal voids in adults with nocturia due to nocturnal polyuria. To meet this objective, the trial should employ efficacy endpoint(s) that measure patient benefit in the treatment of nocturia due to nocturnal

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polyuria; for example, a validated patient-reported outcome instrument that captures the clinical impact of the changes in nocturnal voids. In this new trial, you should also prospectively evaluate hyponatremia monitoring strategies that you intend to recommend for mitigating the risk of hyponatremia in the postmarketing setting.

In your Complete Response, include strategies for mitigating the risk of hyponatremia that would ensure safe postmarketing use of Nocdurna in the intended population.

PRESCRIBING INFORMATION

We reserve comment on the proposed labeling until the application is otherwise adequate. We encourage you to review the labeling review resources on the PLR Requirements for Prescribing Information website including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) — a checklist of 42 important format items from labeling regulations and guidances.

f you revise labeling, use the SRPI checklist to ensure that the PI conforms with format items in regulations and guidances. Your response must include updated content of labeling

21 CFR 314.50(1)(1)()] in structured product labeling (SPL) format as described at ttp://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm.

PROPRIETARY NAME

Please refer to correspondence dated July 31, 2014, which addresses the proposed proprietary name, Nocdurna. 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:

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

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

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

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Page 3 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 NDA 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. A partial response to this letter will not be processed as a

resubmission and will not start a new review cycle.

Under 21 CFR 314.102(d), you may request a meeting or telephone conference 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 FDA Guidance for Industry,

“Formal Meetings Between the FDA and Sponsors or Applicants,” May 2009 at

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U

CM153222.pdf.

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

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If you have any questions, please call Jennifer Johnson, Regulatory Health Project Manager, at (301) 796-2194.

Sincerely,

{See appended electronic signature page} Jean-Marc Guettier, M.D.

Director

Division of Metabolism and Endocrinology Products

Office of Drug Evaluation II Center for Drug Evaluation and Research

Reference ID: 3695148

This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.

JEAN-MARC P GUETTIER 01/30/2015

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