RISK FACTORS 4 In the United States, even after an orphan drug is approved, disadvantage relative to alternative products. In addition, the FDA may subsequently approve another drug for the same any approved products wil l be subject to ongoing regulatory condition if the FDA concludes that the latter drug is not the same requirements for manufacturing, labeling, packaging, storage, drug or is clinically superior in that it is shown to be safer, more advertising, promotion, sampling, record keeping and submission effective or makes a major contribution to patient care. In the of safety, RMP and other post-market information. In the European Union, marketing authorization may be granted to a European Union, our product candidates will be subject to the similar medicinal product for the same orphan indication if: regulatory oversight of the CAT, which makes recommendations • the second applicant can establish that its medicinal product, to the Committee for Medicinal Products for Human Use, although similar to the orphan medicinal product already or CHMP, for recommendation of approval by the European authorized, is safer, more effective or otherwise clinical ly Commission. In the United States, any regulatory approvals superior; that we receive for our product candidates also may be subject to REMS, limitations on the approved indicated uses for which • the holder of the marketing authorization for the original the product may be marketed or to the conditions of approval, orphan medicinal product consents to a second orphan or contain requirements for potential ly costly post-marketing medicinal product application; or testing, including Phase IV clinical trials, and surveil lance to • the holder of the marketing authorization for the original monitor the quality, safety and efficacy of the product. For orphan medicinal product cannot supply sufficient quantities of example, the holder of an approved BLA is obligated to monitor orphan medicinal product. and report adverse events and any failure of a product to Even if we complete the necessary clinical trials, we cannot predict meet the specifications in the BLA. FDA and EMA guidance when, or if, we will obtain regulatory approval to commercialize advises that patients treated with some types of gene therapy a product candidate and the approval may be for a more narrow undergo fol low-up observations for potential adverse events indication than we seek. for as long as 15 years. If a previously unknown safety issue is discovered with a product after approval, the FDA, the EMA or We cannot commercialize a product candidate until the other regulatory authorities may require revisions to the labeling appropriate regulatory authorities have reviewed and approved or approved indications of the product or withdraw approval the product candidate. Even if our product candidates meet of the product entirely. The holder of an approved BLA also their safety and efficacy endpoints in clinical trials, regulatory must submit new or supplemental applications and obtain FDA authorities may not complete their review processes in a timely approval for certain changes to the approved product, product manner and may recommend non-approval or may place labeling or manufacturing process. Advertising and promotional restrictions on approval. In addition, we may experience delays or materials must comply with FDA rules and other applicable rejections as a result of future legislation or administrative action, federal and state laws. In addition, product manufacturers are or changes in regulatory authority policy during the period of subject to payment of user fees and continual review and periodic product development, clinical trials and the review process. inspections by the FDA, the EMA and other regulatory authorities for compliance with current Good Manufacturing Practices, Regulatory authorities also may approve a product candidate for or cGMP, requirements and adherence to commitments made more limited indications than requested, may require precautions in the BLA, Common Technical Document, or CTD, or other or contraindications or they may grant approval subject marketing application. to the performance of costly post-marketing clinical trials or implementation of REMS. In addition, regulatory authorities may If we fail to comply with applicable regulatory requirements not approve the labeling claims that are necessary or desirable following approval of any of our product candidates, a regulatory for the successful commercialization of our product candidates. authority may: Any of the foregoing events could materially harm the commercial • issue a warning letter asserting that we are in violation of the prospects for our product candidates. law; Even if we obtain regulatory approval for a product candidate, • seek an injunction or impose administrative, civil or criminal our products will remain subject to the terms of our approvals and penalties or monetary fines; ongoing regulatory oversight that may limit how we market our products, which could materially impair our ability to generate • suspend or withdraw regulatory approval or revoke a license; revenues. • suspend any ongoing clinical trials; Even if we obtain any regulatory approval for our product • refuse to approve a pending BLA or comparable other candidates, this approval may carry conditions that limit the marketing application (or any supplements thereto) submitted market for the product or put the product at a competitive by us or our strategic partners; GENSIGHT BIOLOGICS – 2017 Registration Document– 27