Kala Pharmaceuticals, Inc.Eysuvis (loteprednol etabonate ophthalmic suspension)

NDA 210933 COMPLETE RESPONSE

Kala Pharmaceuticals, Inc. Attention: Patrick Foster Senior Director, Regulatory Affairs 490 Arsenal Way Suite 120 Watertown, MA 02472

Dear Mr. Foster:

Please refer to your new drug application (NDA) dated and received October 15, 2018, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25%.

We have completed our review of this application, as amended, and have determined that we cannot approve this application in its present form. There is a lack of substantial evidence consisting of adequate and well-controlled investigations, as defined in 21 CFR 314.126, that the drug product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling. Specifically:

a. Study (Trial KPI-121-C-002) failed to demonstrate superiority of loteprednol etabonate ophthalmic suspension, 0.25% for its primary symptom endpoint.

b. Study (Trial KPI-121-C-007) failed to demonstrate superiority of loteprednol etabonate ophthalmic suspension, 0.25% for its primary symptom endpoint.

It is recommended that to demonstrate substantial evidence of efficacy in the intended patient population, data from at least one additional clinical trial be submitted in which loteprednol etabonate ophthalmic suspension, 0.25% demonstrates superiority to its vehicle in the treatment of signs and symptoms of dry eye disease.

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 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 guidance.

Reference ID: 4473649

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If you revise labeling, use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidance. 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.

PROPRIETARY NAME

Please refer to correspondence dated, February 26, 2019, which addresses the proposed proprietary name, Eysuvis. 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 deficiency, include a safety update as described at 21 CFR 314.50(d)(5)(vi)(6). The safety update should include data from all nonclinical and clinical studies/trials of the product under consideration regardless of indication, dosage form, or dose level.

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 the deficiency 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 deficiency outlined in this letter. A partial response to this letter will not be processed as a resubmission and will not start a new review cycle.

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

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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, call Dneera Semidey, Regulatory Project Manager, at (301) 796-3009.

Sincerely, {See appended electronic signature page}

Wiley A. Chambers, MD

Deputy Director

Division of Transplant and Ophthalmology Products Office of New Drugs

Center for Drug Evaluation and Research

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

Reference ID: 4473649

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.

WILEY A CHAMBERS 08/07/2019 03:17:12 PM

Reference ID: 4473649