Sarepta Therapeutics, Inc.: Vyondys

/mportanily, therefore, the possibility of infections did not figure into eteplirsen's risk-benefit calculus at the time of its approval.

Accordingly, the risk is fully applicable to golodirsen, and the 2.3% frequency from eteplirsen's voluntary postmarketing reporting probably represents a conservative estimate of the risk, given the typical under-reporting of spontaneous adverse events.

And again, because there is no proven way to monitor renal function in these patients, we are not aware of a mechanism to provide adequate instructions for use in labeling for golodirsen.

When eteplirsen was granted accelerated approval in 2016, you were required to perform a postmarketing study to verify eteplirsen's clinical benefit.

Patients were to be randomized to the approved dosage of eteplirsen (30 mg/kg weekly) or to a dose 7-fold higher, e.g., 30 mg/kg daily.

"Thus, | am confident that this unique situation will not set a general precedent for drug approvals under the accelerated approval pathway, as the statute and regulations are clear that each situation must be evaluated on its own merits based on the totality of data and information."

First, considering the Center Director's 2016 decision on the accelerated approval of eteplirsen, there would have been support for granting accelerated approval to golodirsen - assuming other important aspects of the two drugs were equal.

The important point here is that the benefit-risk balance with golodirsen differs from the benefit-risk balance that was known for eteplirsen at the time of its accelerated approval.

The risk-benefit profile for eteplirsen was quite different when it was given accelerated approval in 2016, as no risks were evident.

Given that you have established a standard paradigm and design for these types of studies, given that you have relationships with a number of DMD referral centers, and given that some 469 patients have received commercial eteplirsen, it is necessary to ask why you have not initiated your required confirmatory study with due diligence.

Finally, if the drug could be administered without implantation of an indwelling port, the benefit-risk profile could be improved.