The matter of how adhesion of its Viaskin Peanut allergy patch relates to efficacy became a major problem for DBV Technologies SA, which drew a complete response letter (CRL) for the once-daily epicutaneous (EPIT) product.

Shares of the Montrouge, France-based firm (NASDAQ:DBVT) closed Aug. 4 at $2.34, down $1.76, or 43%, in reaction to the CRL for the patch, designed to protect children ages 4 to 11. The FDA wants DBV to modify the patch, which means a new human-factor study; officials also are requiring clinical data for the modified patch. As if that weren’t enough, DBV needs to provide more chemistry, manufacturing and controls (CMC) info, though the agency didn’t cite any safety hitches with the product.

DBV said it will ask for a sit-down with the FDA to find out more, and promised an update afterward to include details about the firm’s cash runway after the recent restructuring. The company in late June made known its plans to scale down spending on clinical and preclinical programs other than Viaskin Peanut. At the end of the first quarter of 2020, the bank account showed €262.4 million (then US$295 million) in cash and cash equivalents. That amount, given the cutbacks, would extend significantly beyond management's previous guidance of the first quarter of 2021.

Wainwright analyst Andrew Fein had been optimistic. “In light of supplementary materials highlighting patch-site adhesion and its relevance to clinical outcome provided to the agency, we maintain our view that concerns on patch adhesion stand to be put to rest,” he wrote in a June 29 report. They weren’t – and trouble had been brewing for a while. In late 2018, the company voluntarily withdrew the Viaskin Peanut BLA following verbal and written word from the FDA about CMC. In March of this year, DBV disclosed that regulators’ questions about the patch continued to stick, and a meeting of the FDA’s Allergenic Products Advisory Committee slated for May 15 was called off. The PDUFA date of Aug. 5 stayed in place, but the setup didn’t bode well, as Wall Street tried to guess the severity of the agency’s skepticism.

Daniel Tasse, CEO, DBV

During a virtual Goldman Sachs conference in early June, analyst Graig Suvannavejh questioned DBV about adhesion. CEO Daniel Tassé said the related data were “part of our pre-BLA package – [they] actually represented a good section of our pre-BLA package sent to the agency back in early 2018.” At the time, the FDA “did not express that they wanted the company to dive deeper into this adhesion data, so it was not a featured element of our BLA,” though such findings are “always attached,” he said. “You know, every last blood pressure taken on patient is part of the dataset that you send to the agency.” DBV has verified that “as long as patients wear the patch for more than 10 hours, they see a significant clinical response,” he said, “and 16 hours or more makes no difference. That seems to be the sweet spot of response here.”

SVB Leerink analyst Joseph Schwartz called the CRL “an unexpected major blow to the company, given the agency will not approve Viaskin’s existing product design, and DBV will likely have to return to the clinic upon modification of the EPIT patch. While prior FDA communications appeared to center around manufacturing and adhesion issues, it is now clear to us that the FDA also had reservations regarding Viaskin Peanut’s previously generated clinical data,” he wrote in a report. DBV’s phase III trial called Pepites failed to clear the 15% lower bound of the 95% confidence interval in the difference in response rates between the active and placebo arms, he noted. “Although we continue to see value in the overall approach of EPIT for peanut allergy, it is unfortunate that the missteps of DBVT’s prior [management] are coming back to haunt the current company,” Schwartz said, adding that his model for the company is under review.

Jefferies’ Eun Yang, in her take on the news, said that “given the series of delays/issues” for Viaskin Peanut, the CRL “does not come as a big surprise. Nevertheless, the FDA’s request for additional data, despite DBV's submission of more data in April, raises uncertainty for regulatory success and its timeline.” She placed the odds of approval at less than 50%.

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