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Background Analysis: US FDA Advisory Committee to Review AllerQuest’s PRE-PEN PLUS Skin Test Kit for Penicillin Allergy – MAR 27, 2019 (PADAC)


The US FDA has scheduled a Pulmonary-Allergy Drugs Advisory Committee (PADAC) for Wednesday, March 27, 2019, to discuss a new drug application (NDA) for PRE-PEN PLUS, a proposed skin test kit for penicillin allergy by AllerQuest, LLC (AllerQuest).

Indication Background

Among the 10% of the US population who self-report as having a penicillin allergy, it is estimated that only 10 to 15% have a true immunoglobulin E-mediated allergy. The use of penicillin to treat bacterial infections may be being inappropriately restricted, with an increased use of broad spectrum antibiotics, possibly leading to an increased risk for adverse events and poorer antibiotic stewardship.

Product Background

Description of Product

PRE-PEN PLUS is a skin test kit under review at the FDA that is designed to detect immunoglobulin E (IgE) sensitization to penicillin antigens. AllerQuest proposes the product be indicated “to detect IgE sensitization to penicillin antigens and reliably rule out the potential for immediate life-threatening penicillin allergic reactions with a high degree of probability in patients with history of possible IgE-dependent penicillin allergy.” The kit combines the company’s approved product, PRE-PEN (benzylpenicilloyl polylysine for injection), which tests for the major determinant of penicillin allergy, with a mixture of the following minor determinants: penicillin G potassium; penicilloic acid; penilloic acid; and amoxicillin sodium.

PRE-PEN is indicated as follows:

PRE-PEN is indicated for the assessment of sensitization to penicillin (benzylpenicillin or penicillin G) in patients suspected to have clinical penicillin hypersensitivity. A negative skin test to PRE-PEN is associated with an incidence of immediate allergic reactions of less than 5% after the administration of therapeutic penicillin, whereas the incidence may be more than 50% in a history-positive patient with a positive skin test to PRE-PEN. These allergic reactions are predominantly dermatologic. Whether a negative skin test to PRE-PEN predicts a lower risk of anaphylaxis is not established. Similarly, when deciding the risk of proposed penicillin treatment, there are not enough data at present to permit relative weighing in individual cases of a history of clinical penicillin hypersensitivity as compared to positive skin tests to PRE-PEN and/or minor penicillin determinants.

Clinical Trials

ClinicalTrials.Gov lists a completed Phase 3 trial for PRE-PEN PLUS (ID: NCT01818336), which includes the study results. The trial was a prospective, open-label investigation in 481 subjects at least 18 years of age with a self-reported history of possible IgE-dependent penicillin hypersensitivity. The primary endpoint was the negative predictive value (NPV), which was estimated as percentage of history-positive subjects with negative skin tests from the kit (as confirmed with an overall negative result for the skin puncture/intradermal testing) who do not experience an IgE-dependent hypersensitivity reaction within 72 hours of the oral amoxicillin challenge. ClinicalTrials.Gov reports that the NPV in the trial was demonstrated to be 98.0%, with a 95% confident interval ranging from 96.6 to 99.4%.

Regulatory Considerations

The FDA meeting announcement says the discussion will include study design considerations, the contribution of each of the components, and whether the submitted data provide substantial evidence of efficacy.

Regulatory Background

US Regulatory Background

Date unknown – NDA 208646 submission date

Ex-US Regulatory Background

Tarius has not found any publicly-available information regarding ex-US regulatory filings.

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: AllerQuest, LLC Drug Name: PRE-PEN PLUS: PRE-PEN (benzylpenicilloyl polylysine for injection) with penicillin G potassium, penicilloic acid, penilloic acid, and amoxicillin sodium Drug Class: skin allergy test Indication: penicillin allergy detection

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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.