DBV Technologies SA officials took pains to reassure investors that data wanted by the FDA with regard to the BLA for Viaskin Peanut allergy therapy are already in hand and need only be turned over to the agency, but that didn’t stop shares (NASDAQ:DBVT) from sliding 55.7%, or $2.93, to close March 17 at $2.33.

The regulatory tie-up is not Viaskin Peanut’s first. In late 2018, DBV voluntarily withdrew the BLA, following verbal and written communications with the FDA. DBV concluded the package, submitted Oct. 18, 2018, lacked sufficient detail regarding data on manufacturing procedures and quality controls, while noting that gatekeepers did not cite concerns related to the clinical module.

Montrouge, France-based DBV said U.S. regulators lately came up with questions about the efficacy that include patch-site adhesion, and they nixed a meeting of the Allergenic Products Advisory Committee (APAC) slated for May 15. Viaskin Peanut’s PDUFA date of Aug. 5 apparently remains unchanged but may be affected by the latest hitch, DBV said.

Daniel Tasse, CEO, DBV

CEO Daniel Tasse said during a public conference call that DBV “very much believe[s] that patch adhesion is not a factor in clinical outcome,” adding that his firm is “looking forward to engaging with the agency on discussing exactly that.” He pointed to three-year data from the study called People, which gained a “pretty remarkable clinical response, which obviously we would not achieve if the kids were not adherent to therapy.” Viaskin Peanut is meant for children ages 4 to 11.

The People study is the open-label extension (OLE) part of the failed phase III experiment called Pepites. The Pepites trial randomized 356 participants, between the ages of 4 and 11, in a 2-to-1 ratio to receive either a daily 250-mcg dose of peanut protein over 12 months, delivered through an epicutaneous patch, or placebo. The primary endpoint was the percentage of treatment responders, defined as those with post-treatment eliciting dose of 1,000 mg or greater in a double-blind food challenge when the baseline eliciting dose was over 10 mg or a post-treatment eliciting dose of 300 mg or more when the baseline eliciting dose was 10 mg or less. More than one-third – 35.3% – of those in the treatment arm responded to therapy, whereas less than one-sixth – 13.6% – of those in the control arm did.

After three years of treatment in the OLE People effort, more than 75% of patients increased their eliciting dose (ED) of peanut required to provoke an allergic reaction during a food challenge from baseline. In all, 51.8% of patients reached an ED of at least 1,000 mg of peanut protein, showing an increase relative to one year.

Tasse said DBV “has been in constant dialogue with the FDA regarding COVID-19 to understand any impact to our BLA timelines for inspections and full review.” Late in the day on March 13, the firm “received a nonspecific email indicating concerns with the BLA that may impact the advisory committee meeting date.” DBV asked for spoken clarification, which regulators provided. The upshot is that “information that we have on file should address these new questions,” he said. “Importantly, during the pre-BLA meeting and subsequent discussions, the FDA did not raise any concerns regarding efficacy related to patch adhesion.”

H.C. Wainwright analyst Andrew Fein called the latest development “potentially a non-issue,” writing in a report that “our initial concerns centered on Viaskin not meeting its pre-determined 15% lower bound confidence interval between treatment groups, which was reported at 12.4%, although management highlighted this was not the concern expressed by the agency.” Instead, the FDA turned out to be concerned about adhesion, which DBV can address fairly easily with the People results and other data, in Fein’s view. “Why not include these data in the original BLA submission for Viaskin Peanut, and avoid prospective adhesion questions altogether?” he asked rhetorically, with a nod to management’s characterization of the BLA as “a concise package focused on patch efficacy,” about which “any question of adhesion [regarded as] a nuance to their FDA discussion.” Fein cited high patient compliance with Viaskin Peanut, though some children scratch as a result of site irritation. DBV said that “most protein comes off the patch and can be delivered within 12 hours, without concern for the patch falling off subsequently,” Fein wrote. He maintained his buy rating with a $25 price target.

Three to six-month PDUFA delay?

The Viaskin platform is based on what DBV has dubbed epicutaneous immunotherapy, or EPIT, a method of delivering biologically active compounds to the immune system through intact skin. Food allergies programs include ongoing trials with Viaskin Peanut as well as Viaskin Milk, and preclinical development of Viaskin Egg. DBV is also pursuing a proof-of-concept trial of Viaskin Milk for the treatment of eosinophilic esophagitis, and exploring potential applications of its platform in vaccines and other immune diseases.

Fein recalled his firm’s peanut allergy survey across 100 allergists in November 2019. Those polled expected their treated peanut allergy patients to grow by about 59% from the current year to five years out. “We determined that a majority of surveyed physicians (64%) consider themselves early adopters, prescribing a drug 0-3 months following approval, and a majority (52%) currently used oral immunotherapy,” he wrote. Fein found a “fundamental distinction” between DBV’s therapy and Brisbane, Calif.-based Aimmune Therapeutics Inc.’s oral Palforzia (peanut [Arachis hypogaea] allergen powder-dnfp), the first approved treatment for peanut allergy. Palforzia offers “high reported efficacy [but] with greater allergic reaction risk,” in his view.

Aimmune said that, following the release of the medication lots by the FDA, specialty pharmacies recently began shipping Palforzia initial dosing kits to allergists for in-office administration to their peanut-allergic patients, ages 4 to 17, with a confirmed diagnosis of peanut allergy. Approved Jan. 31, Palforzia on Sept. 16, 2019, gained the blessing of an APAC panel.

RBC Capital analyst Kennen MacKay, who covers Aimmune, said in a report that DBV’s best-case scenario is a three- to six-month delay in the original PDUFA dates, “while in a worst-case scenario, the detailed dataset could show issues with patch adhesion, negatively affecting efficacy, and even worse, minimal efficacy with the patch itself. These scenarios could provide further upside to our current U.S. Palforzia sales estimates of $54 million for fiscal year 2020.”