The Food and Drug Administration’s rejection Monday of Sarepta Therapeutics’ second drug for Duchenne muscular dystrophy came as a surprise to many. It also led investment bank analysts to offer their own hypotheses for why the FDA reached that decision.

Shares of the Cambridge, Massachusetts-based biotech company were already down 13 percent after hours on the Nasdaq following the announcement that the FDA had issued a complete response letter, or CRL, for the drug Vyondys 53 (golodirsen), in DMD amenable to exon 53 skipping. On Tuesday morning, they dropped 18 percent from their Monday closing price when markets opened and remained down throughout the day.

In a statement, Sarepta CEO Doug Ingram expressed surprise at the CRL, but he also noted that the issues that the letter brought up were not raised by the FDA as the agency reviewed the application. In particular, the company said the CRL generally cites two concerns. One was renal toxicity in preclinical models based on dose level 10 times that of the one used in humans, which was nevertheless not observed in the 39-patient Phase I/II Study 4053-101. The other issue was infections at intravenous infusion ports.

Sarepta did not immediately respond to a request for comment.

“In our view, [Sarepta] is being slapped on the wrist for the prior questionable accelerated approval of Exondys 51,” wrote SVB Leerink analyst Joseph Schwartz in a note to investors, referring to the company’s marketed product, eteplirsen, for exon 51 skipping-amenable DMD.

The accelerated approval of Exondys 51 in late 2016 was highly controversial. The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee had recommended against the approval on the basis of surrogate endpoint data for a small number of boys. Nevertheless, FDA Center for Drug Evaluation and Research Director Janet Woodcock overruled FDA reviewers’ objections and approved the drug anyway, advocating flexibility in the face of a life-threatening disease that lacked treatments. Many have suspected that the FDA’s decision stemmed at least in part from pressure from the DMD patient community.

Other analysts had their own ideas as well.

“The real driver(s) of the atypical Golodirsen CRL will continue to be a debate based on limited public disclosure of the granularity of facts, but the macro take home is clear in our minds – there is a regulatory ‘raising of the bar,’” wrote a group of analysts at Evercore ISI.

Cowen analyst Ritu Baral wrote that the CRL was not anticipated, given that Vyondys 53 and Exondys 51 both have similar backbone chemistry, and the latter has not shown serious issues related to kidney toxicity or infections at infusion ports.

“While the CRL was unexpected, we believe some conservative senior elements of the FDA, key to the final approval, view the overall risk-benefit profile of the drug as different than Exondys or even casimersen,” Baral wrote, referring to another investigational drug, for DMD amenable to exon 45 skipping. In particular, she wrote, it’s the renal signal that seems to have driven the FDA decision, and there is a well-documented risk of renal toxicity observed with antisense oligonucleotide drugs chemically different from Sarepta’s. The infection risk was viewed as easily addressable in the near term.

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