DBV Soars As Path For Peanut Allergy Patch Approval Clears
Positive FDA Feedback After Earlier Rejection
Executive Summary
The French biotech's chances of competing with Aimmune's Palforzia in the peanut allergy market have been boosted after US regulators decided that a fresh Phase III trial for the Viaskin Peanut patch would not be required for resubmission.
DBV Technologies' peanut allergy patch has been on shaky ground since a rejection from US regulators in August last year but the path to potential approval has become clearer after the French firm's positive meeting with the Food and Drug Administration.
The future for DBV looked bleak last summer when the FDA issued a complete response letter to the biologics license application for Viaskin Peanut, the firm's once-daily epicutaneous immunotherapy (EPIT) patch to treat peanut allergies in children aged four to 11 years. The agency identified "concerns regarding the impact of patch-site adhesion on efficacy and indicated the need for patch modifications, and subsequently a new human factor trial" and requested supplementary clinical data.
The CRL did not clarify the type of data that would be required to support a resubmission and there were fears that a fresh Phase III trial may be needed. However, those fears have been allayed after feedback from a Type A meeting request "provides a well-defined regulatory path forward, " DBV said.
Most significantly, the FDA has agreed with DBV's position that a modified Viaskin Peanut patch should not be considered as a new product entity provided the occlusion chamber and peanut protein dose (250µg, approximately 1/1000 of one peanut) remained the same and performed similarly to the original patch. To demonstrate this, the Montrouge-based company will compare the uptake of peanut protein between the patches in allergic children aged 4-11 years in a bridging study and then conduct a six-month controlled trial evaluating the safety and adhesion of the modified patch.
CEO Daniel Tassé said, “We are very encouraged by the positive feedback received from the FDA and we appreciate the clarity provided.” He added that the firm would advance a remediation plan for Viaskin Peanut "and refile our BLA as soon as possible." DBV plans to initiate the selection of modified prototype patches in the first quarter of 2021 and submit the protocol for the safety and adhesion trial to the FDA for review in the second quarter before initiating the trial.
Tassé's enthusiasm was shared by investors and shares in DBV, which is listed on the NASDAQ as well as the Euronext, had soared over 41% on the Paris exchange to close at €8.65 on 15 January.
Analysts were also relieved and Jonathan Wolleben at JMP Securities issued a note on 15 January saying that initial feedback from the FDA "is better than our base-case scenario," He added that importantly, the agency did not ask for a double-blind, placebo-controlled food challenge (DBPCFC), ie, the actual ingestion of peanut which could cause high levels of anxiety for patients and their parents; having no DBPCFC should accelerate enrolment "and points to the FDA’s level of comfort with Viaskin Peanut’s known efficacy profile," Wolleben wrote.
Given the FDA’s request is for a six-month rather than one-year study, JMP has moved up its expectations for a US launch to 2023 from 2024 "which may still prove conservative depending on the speed of FDA interactions and trial enrolment."
Over at SVB Leerink, Joseph Schwartz agreed that the feedback from the FDA "provides a well-defined regulatory path forward" in the US while noting that in the EU, the marketing authorization application for Viaskin Peanut was validated in November. He noted that DBV had been working on redesigning the patch even before the CRL was issued, given that in March 2020 the FDA first voiced concerns that the detachment of patches may lead to less than ideal efficacy.
Schwartz said that the company had "several levers that can be pulled to modify the patch," such as changing the shape from a square to an oval or circle, making it less likely to catch on something and modifying the adhesive on the foam to increase its strength. "We are optimistic that the company will have several promising options to choose from as it begins the prototype selection process," he said, adding that "we look forward to further details on next steps to get this much-needed – and long delayed – product to market."
Restructuring Plan
DBV has also been getting its financial house in order and a restructuring plan announced in June last year continues to be implemented. The company is to reduce its headcount by more than 200, leaving a worldwide team of 90 employees, a move which CEO Tassé said would "yield a leaner organization, enable us to achieve greater financial flexibility and allow us to best position ourselves as we navigate the late stages of clinical development.” As of September 30, 2020, DBV had cash and equivalents of €189.1m which, combined with the cost reduction measures, should fund operations well into the second half of 2022.
If all goes well, Viaskin Peanut will finally compete with Aimmune Therapeutics, Inc.’s peanut allergy oral immunotherapy Palforzia (defatted powder of Arachis hypogaea), which was approved in the US almost a year ago to mitigate allergic reactions that may occur with accidental exposure to peanut in patients ages four to 17 years. However, it was associated with a high rate of systemic allergic reactions and epinephrine use in clinical trials so the FDA required Aimmune, recently acquired by Nestle Health Science, to implement a risk evaluation and mitigation strategy. (Also see "US Approval For Peanut Allergy Therapy Palforzia" - Scrip, 3 Feb, 2020.) (Also see "Nestle, Bullish On Palforzia, To Buy Remainder Of Aimmune" - Scrip, 31 Aug, 2020.)
Last month, the European Commission approved Palforzia and launches in Germany and the UK are planned in May this year. Up to 1.6% of children in Europe live with peanut allergy. (Also see "Aimmune's Peanut Immunotherapy Palforzia Gets CHMP Backing" - Scrip, 19 Oct, 2020.)