Date: May 16, 2017

Director, Center for Biologics Evaluation and Research (CBER)
Food and Drug Administration

RE: Original Biologics License Application (BLA) for LUXTURNA™ (voretigene neparvovec)
STN: 125610/0
IND: 13408

Dear Director,

On behalf of Spark Therapeutics, Inc., I am pleased to submit this Biologics License Application (BLA) for LUXTURNA™ (voretigene neparvovec), an adeno-associated virus (AAV) vector-based gene therapy for the treatment of patients with vision loss due to confirmed biallelic RPE65 mutation-associated retinal dystrophy.

This BLA is being submitted in the electronic Common Technical Document (eCTD) format. This submission represents the final part of a rolling submission, as agreed with the Agency in our Pre-BLA meeting on March 25, 2016. The BLA has been submitted in three parts:
- Part 1: Non-clinical Module (Module 4) submitted on April 26, 2016.
- Part 2: Clinical Module (Module 5) submitted on February 21, 2017.
- Part 3: Chemistry, Manufacturing, and Controls (CMC) Module (Module 3), included with this final submission.

LUXTURNA has been granted Orphan Drug, Breakthrough Therapy, and Rare Pediatric Disease designations. In accordance with Section 526 of the FD&C Act, we hereby request Priority Review for this application, given that LUXTURNA, if approved, would represent a significant improvement in the safety or effectiveness of the treatment of a serious condition.

This submission is based on a comprehensive development program, including a pivotal Phase 3 study (Study 301) that met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in functional vision. We believe the data presented in this BLA provide substantial evidence of the efficacy and safety of LUXTURNA for the proposed indication. 

We trust that this submission is complete and sufficient for a full review. We look forward to working with the Agency during the review process.

Sincerely,

[Fictional Name]
John Doe, PhD
Chief Regulatory Officer
Spark Therapeutics, Inc.