treatment goals

Prota’s proprietary peanut oral immunotherapy (PRT120) is an investigational new drug being evaluated for its capacity to induce sustained unresponsiveness, also referred to as remission of allergy.

Several possible clinical outcomes have been described for the evaluation of food immunotherapy treatments:

  • Desensitization is defined as a temporary increase in reaction threshold to a food allergen while receiving active therapy and might equate to protection from accidental ingestion1. As the immune changes supporting desensitization are only temporary, so continued protection from desensitization requires indefinite maintenance therapy. Desensitization can be assessed by performing a food challenge during treatment and showing an increase in the reaction threshold compared to before treatment.
  • Sustained Unresponsiveness (also referred to as Remission) is defined as the absence of clinical reactivity that is maintained even after stopping treatment for a period of time1. Remission has been suggested as a better way to describe sustained unresponsiveness in the setting of food allergy immunotherapy1. Sustained unresponsiveness or remission is supported by longer-lasting immune changes involving re-direction of the allergen-specific immune response away from allergy towards tolerance, which leads to significantly reduced blood levels of allergen-specific IgE (the cause of IgE-mediated food allergy)2,3. These lasting immune changes may allow free intake of the allergen without the need for ongoing maintenance therapy. Studies have shown that patients who achieved sustained unresponsiveness or remission experience significantly improved health-related quality of life compared with those who were only desensitized and those who remained allergic3,4. Sustained unresponsiveness or remission can be assessed by performing a standard diagnostic food challenge weeks or months after treatment is stopped (while avoiding the allergen) and showing no reaction. The period of time between stopping treatment and testing for remission should be long enough for desensitization effects to have waned.
  • Persistent sustained unresponsiveness / Persistent remission. When sustained unresponsiveness or remission of allergy is still present years after stopping treatment, with ad libitum allergen intake in the intervening period, this is referred to as “persistent sustained unresponsiveness” or “persistent remission”. This long-term outcome can be assessed by performing a food challenge several years after stopping treatment, with allergen avoidance reinstated for weeks or months prior to the food challenge. Such enduring protection years after treatment may suggest ‘possible’ tolerance, however permanence of protection cannot be proven.
  • Tolerance is defined as complete and permanent resolution of clinical response following exposure to any amount of the allergenic food after termination of therapy. There is currently no consensus on how to assess for the presence of tolerance since ‘permanence’ of an effect is difficult to establish within the context of a clinical study.

Prota Therapeutics is focused on the evaluation of their investigational lead product, PRT120 for the primary outcome of remission of peanut allergy (sustained unresponsiveness). Remission of peanut allergy allows a person who was previously allergic to peanut to now eat peanut freely in their diet. This is possible because the protection provided with remission persists even when there is no peanut intake for weeks or months.

The Food Allergy Treatment Landscape

 

PRT120 MECHANISM OF ACTION >

References:

  1. W. Burks, H. A. Sampson, M. Plaut, G. Lack and C. A. Akdis. Treatment for food allergy. J Allergy Clin Immunol 2018 Vol. 141 Issue 1 Pages 1-9. Accession Number: 29307409 DOI: 10.1016/j.jaci.2017.11.004
  2. S.E. Ashley, A. C. Jones, D. Anderson, P. G. Holt, A. Bosco and M. L. K. Tang. Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks. Allergy 2022 Vol. 77 Issue 10 Pages 3015-3027. Accession Number: 35615783 PMCID: PMC9790273 DOI: 10.1111/all.15324
  3. Loke, F. Orsini, A. C. Lozinsky, M. Gold, M. D. O’Sullivan, P. Quinn, et al. Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial. Lancet Child Adolesc Health 2022 Vol. 6 Issue 3 Pages 171-184. Accession Number: 35123664 DOI: 10.1016/S2352-4642(22)00006-2
  4. Loke, X. Wang, M. Lloyd, S. E. Ashley, A. C. Lozinsky, M. Gold, et al. Allergy 2024. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study. Accession Number: 39099231 DOI: 10.1111/all.16262