(iii) a rolling review process whereby the FDA may consider reviewing portions of a BLA before the sponsor submits the complete application. Product candidates designated as breakthrough therapies by the FDA may be eligible for priority review if supported by clinical data.
Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to products considered for approval under conventional FDA procedures and, in any event, does not assure ultimate approval by the FDA. In addition, even though AVXS‑101 has been designated as a breakthrough therapy product candidate, the FDA may later decide that it no longer meets the conditions for designation or decide that the time period for FDA review or approval will not be shortened.
Access to the PRIME initiative is granted by the European Medicines Agency, to support the development and accelerate the review of new therapies to treat patients with unmet medical need. The receipt of this access for a product candidate may not result in a faster development process, review or approval compared to products considered for approval under conventional EMA procedures and, in any event, does not assure ultimate approval by the EMA. In addition, even though AVXS‑101 has been granted access to PRIME, the EMA may later decide that it no longer meets the conditions for such access.
Success in preclinical studies or early clinical trials, including in our Phase 1 clinical trial of AVXS-101, may not be indicative of results obtained in later trials or provide support for submission of a marketing application.
Results from preclinical studies or early stage clinical trials such as our Phase 1 clinical trial are not necessarily predictive of future clinical trial results, and interim results of a clinical trial are not necessarily indicative of final results. AVXS‑101 may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies and our Phase 1 clinical trial. The clinical trial process may fail to demonstrate that AVXS‑101 is safe for humans and effective for indicated uses. This failure would cause us to abandon AVXS‑101. Our Phase 1 clinical trial involved a small patient population and the duration of treatment has been relatively short. In addition, our Phase 1 clinical trial of AVXS‑101 did not include a placebo control. Because of the small sample size and other changes to the design of the clinical trial that we implemented in our pivotal trial based on feedback from the FDA during our September 2016 Type B meeting and the meeting minutes, the results of our Phase 1 clinical trial may not be indicative of results of future clinical trials, including our pivotal trial.
There is a high failure rate for drugs and biologic products proceeding through clinical trials. Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late‑stage clinical trials even after achieving promising results in preclinical testing and earlier‑stage clinical trials. Data obtained from preclinical and clinical activities are subject to varying interpretations, which may delay, limit or prevent regulatory approval. In addition, we may experience regulatory delays or rejections as a result of many factors, including due to changes in regulatory policy during the period of our product candidate development. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. Frequently, product candidates that have shown promising results in early clinical trials have subsequently suffered significant setbacks in later clinical trials. In addition, the design of a clinical trial can determine whether its results will support approval of a product and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced. Our company has limited experience in designing clinical trials and we may be unable to design and execute a clinical trial to support regulatory approval. In our Phase 1 clinical trial of AVXS‑101, we used event‑free survival as the efficacy endpoint, with an “event” defined as death or at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively. Although none of the patients who received the proposed therapeutic dose of AVXS‑101 experienced an event as of August 7, 2017, one patient in the low‑dose cohort experienced an event as classified by an independent Data Safety Monitoring Board, that was determined by independent review to represent progression of disease and not to be related to the use of AVXS‑101. Clinical trials are inherently unpredictable, and there are no assurances that these patients enrolled in the Phase 1 trial will not experience an event in the future. Furthermore, although the FDA indicated its preference for survival, such as time to an event, as a co‑primary endpoint for the pivotal trial, there is no assurance that the FDA will determine event‑free survival to be an acceptable efficacy