Professor Mimi Tang discusses multi-year follow up from the PPOIT-003 Phase IIb programme and how these data help clarify distinct post-treatment clinical states, including remission and desensitisation, and their implications for durability, adherence, and real-world patient experience once structured therapy is complete.

 Recent multi-year data from the PPOIT-003 and PPOIT-003LT programmes demonstrate that PRT120 has the potential to deliver durable protection in children with peanut allergy, including a clinically meaningful remission state in which protection persists after treatment ends. These findings differentiate PRT120 from approved approaches and those in late-stage development which rely on continuous dosing because protection diminishes when treatment stops. This distinction highlights PRT120’s potential to address a major unmet need in food allergy care and support its continued advancement in late-stage development and regulatory evaluation. 

The current landscape of peanut allergy treatments 

Despite the availability of recently approved therapies, peanut allergy remains a chronic condition with an ongoing risk of unpredictable allergic reactions. Even with careful allergen avoidance, accidental exposures remain common, necessitating sustained vigilance and active management¹ For most individuals, the condition is lifelong, resulting in a substantial and continuing burden on patients and families. 

 Experience with first-generation oral immunotherapy has highlighted the limitations of approaches that rely on continuous, indefinite dosing to maintain protection. While these therapies can increase tolerance during active treatment, protection diminishes once dosing stops, adherence can be difficult to sustain long term, and the real-world burden on families remains substantial. 

 These challenges do not invalidate immunotherapy as a strategy—rather, they underscore the need for next-generation oral immunotherapy designed to induce durable protection that persists after treatment ends. 

 Clinicians, scientists, and regulators increasingly distinguish between two post-treatment outcomes: desensitisation, in which protection depends on ongoing dosing, and remission, in which protection persists after treatment has stopped². This distinction is critical because remission carries fundamentally different implications for durability, adherence, and real-world functioning.  

It is critical to understand how desensitisation and remission diverge over time; yet few studies have followed participants beyond the first year, and long-term data are limited1. As a result, key questions remain regarding the durability of clinical protection, the sustainability of maintenance dosing, and how the allergen-specific immune response evolves following treatment cessation. The investigator-initiated PPOIT-003 programme, and its long-term extension (PPOIT-003LT), are among the few studies to follow children for several years after treatment completion, providing critical insight into long-term treatment outcomes over time. 

This Phase IIb programme evaluated PRT120, a novel finite 18-month peanut oral immunotherapy regimen designed to deliver durable protection beyond the treatment period. The programme’s objective was to assess whether treatment could induce desensitisation or remission, and to characterise how patients achieving each outcome fared after treatment cessation, including patterns of peanut intake, reactions and changes in quality of life.  

Inside the PPOIT-003 Phase IIb and long-term studies: design rationale 

The Phase IIb trial (PPOIT-003) and its extension study (PPOIT-003 LT) were conducted across three tertiary paediatric centres. The primary findings showed that PRT120 treatment produced significantly higher rates of both desensitisation and remission compared with placebo at the end of treatment³. Follow-up data out to two years post-treatment further showed durable differences in ingestion patterns and reactions between children who achieved remission as compared to desensitisation without remission⁴. 

In the PPOIT-003 trial, 201 children were randomised to receive 18 months of active therapy or placebo. At the completion of treatment, a standardised 5-gram peanut protein double blind oral food challenge was performed to assess the level of protection that was achieved (i.e. the amount of peanut that could be tolerated). Children who passed this first challenge underwent a second challenge eight weeks later to determine whether their protection persisted after treatment withdrawal.  

This two-step evaluation defined three clinical outcome categories. 1) Remission: sustained tolerance of the full 5-gram peanut challenge after treatment cessation. 2) Desensitisation without remission: tolerance of the full 5-gram challenge with treatment that waned once dosing was stopped, indicating a requirement for continued daily peanut intake to maintain protection. 3) Persistent allergy: children who were unable to tolerate the end-of-treatment 5-gram challenge.  

Post-treatment peanut ingestion advice was tailored according to the clinical outcome achieved: Children with remission were told to eat peanut ad libitum, without specific instructions on amount or frequency of intake; children who were desensitised without remission were instructed to eat two peanuts daily to maintain their protection; and children with persistent allergy were asked to continue with strict peanut avoidance.  

Children who completed the Phase IIb study were eligible to rollover to the PPOIT-003LT extension study which follows participants through to six years after treatment completion.   

Interpreting the Phase IIb end of treatment findings 

 The PPOIT003 Phase IIb trial showed that 74% of children receiving PRT120 treatment were able to tolerate the full 5-gram challenge at the end of treatment, compared to only 5% in the placebo group. This demonstrated clinically meaningful increases in reaction thresholds and a high level of protection at the end of treatment. 

Importantly, approximately half of the PRT120-treated children also passed the second challenge, indicating that they had achieved remission—their protection persisted even after treatment was stopped. These findings suggest that PRT120 can induce a durable, off-treatment protective state that does not rely on lifelong maintenance dosing. 

The study also examined immunologic changes induced by treatment. Findings provide compelling evidence that PRT120 fundamentally reprogrammes allergen-specific immune pathways, resulting in substantial and durable reductions in serum levels of peanut-specific IgE; greater than 85% reduction that persisted out to 12 months post-treatment.  

The long-term follow-up: What year three data reveal about distinct OIT outcomes 

Long-term outcomes to Year-2 post-treatment have been published previously and preliminary findings from the Year-3 post-treatment assessment were presented at the 2025 European Academy of Allergy Asthma and Clinical Immunology Annual Scientific Congress.  

Peanut ingestion patterns 

Most children who had achieved remission were still freely consuming peanut as part of their regular diet, without the structure of ongoing therapeutic dosing, at three years post-treatment. Consistent with earlier one and two-year post-treatment assessments, most children in remission consumed moderate to large amounts at least once or twice a week. These participants were not avoiding peanut and their dietary patterns resembled free eating rather than treatment. 

Children who were desensitised without remission showed more variation. Just under half continued daily ingestion as recommended, but 69% approximately three-quarters described increasing difficulty maintaining the daily routine by Year 3. This aligns with the known real-world challenges of adherence to long-term daily therapy, particularly as children age and routines change. 

Children who remained allergic continued to avoid peanut. Interestingly, these children reported less frequent accidental exposures than what has been described in community follow-up studies (13% vs. 45% in the preceding 12 months). 

Reaction rates and severity 

Patterns of reaction to peanut diverged meaningfully across clinical outcome groups, reinforcing that remission represents a more stable and protective long-term state than desensitisation alone. Children in remission experienced very few reactions and there were no moderate or severe reactions in Year 2 and Year 3. There were also no reported instances of rescue epinephrine use in this group in Year 2 and Year 3, suggesting durable protection over the observed follow up period that allowed safe intake of peanut ad libitum. 

Children in the desensitised without remission category experienced higher reaction rates, with the proportion of children reporting reactions being twice that of the remission group in all post-treatment years examined. Furthermore, in each year of follow up, around a quarter of reactions in children who were desensitised without remission were moderate or severe events; and between 5% and 8% of children reported rescue epinephrine use. Only a third of reactions involved cofactors such as exercise or illness, which is consistent with broader food allergy literature. This pattern reinforces that continued daily dosing provides protection but does not eliminate variability in day-to-day thresholds that can lead to unexpected and potentially serious reactions. 

Around 10% of children who remained allergic reported accidental exposures leading to reactions each year, underscoring that the absence of treatment leaves individuals vulnerable to unexpected reactions. 

What this means scientifically 

Together, these findings illustrate that remission represents a distinct clinical state associated with robust, real-world protection in the absence of ongoing treatment. Children in remission maintain stable reaction thresholds and very low reaction rates while incorporating peanut into their regular diet. 

In contrast, desensitisation requires continued daily peanut exposure to sustain elevated thresholds. Adherence therefore becomes a critical determinant of long-term outcome, and daily dosing poses practical challenges for many families over time. 

The Year 3 analysis provides an important mid-term perspective that complements earlier findings, strengthens understanding of how protection behaves in everyday life, and underscores the importance of distinguishing between clinical outcomes achieved at the end of treatment. It also contributes meaningfully to the limited body of multi-year oral immunotherapy data currently available. 

Quality of life as a technical outcome measure 

Quality of life serves as a complementary patient-reported outcome which captures aspects of daily living that are not visible in challenge-defined efficacy endpoints. Assessment of quality of life using the validated FAQLQ-PF has shown significant improvements following PRT120 treatment compared to placebo, with magnitudes of improvement well exceeding the minimal clinically important difference at both one and two years post-treatment (analysis of year three post-treatment data is underway)⁵. These improvements largely reflected reduced dietary restrictions, lower anxiety about accidental exposure, and greater participation in everyday activities, provided by achieving remission.  

In the long-term follow-up, children who had achieved remission continued to demonstrate the largest and most sustained improvements in validated quality-of-life measures. Quality of life improvements remained significantly greater compared with children who were desensitised without remission as well as those who remained allergic. The magnitude of improvement in quality of life also consistently exceeded the minimal clinically important difference, indicating a clinically meaningful and durable improvement in everyday functioning.  

Interestingly, children who were desensitised without remission did not experience significant quality of life improvement until Year 3, and the magnitude of benefit was smaller than that observed in the remission group. This suggests that modest benefits may emerge over time for those who are desensitised, whereas achieving remission delivers substantial quality of life improvements within the first-year post-treatment.  

Taken together, these findings suggest that remission represents a distinct biological outcome that can deliver meaningful benefit to patients—sustained improvements in daily living, confidence, and dietary freedom—which are not provided by desensitisation. The alignment between clinical protection and measurable changes in quality of life supports the value of understanding remission and desensitisation as separate outcomes. 

Implications for OIT design and development 

These long-term findings underpin a broader shift in oral immunotherapy development—from maintenance-dependent approaches toward finite regimens designed to achieve durable, off-treatment protection. 

Three key takeaways emerge. First, achieving a remission state, which allows children to discontinue therapy and still retain protection, appears to provide stable and durable benefits that so far have been sustained out to three years after stopping treatment. Programmes that aim for remission may allow removal of allergen avoidance, leading to meaningful improvements in day-to-day quality of life.  

Second, long-term follow-up is essential. Shorter studies capture the immediate therapeutic effect but do not provide insight into durability of treatment effect, adherence patterns, or changes in reaction severity. The PPOIT-003LT three-year interim analysis provides valuable information, and five-year post-treatment data is forthcoming. 

Finally, the field will benefit from clearer endpoint definitions that recognise the biological and experiential differences between remission, desensitisation, and persistent allergy. These distinctions have implications for regulatory discussions, programme design, and long-term expectations for patients and families. 

The path forward: scientific questions that remain 

While the Year 3 data are highly informative, several important scientific questions remain. These include the optimal duration of maintenance dosing to deliver a remission outcome, the immunologic characteristics that predict remission, and the patient profiles most likely to achieve sustained protection. Emerging biomarkers may ultimately help address these questions, but they remain an active and evolving area of investigation. 

The field is also continuing to explore how real-world adoption of oral immunotherapy will differ from controlled clinical trial settings. Translating multi-year efficacy into routine community practice introduces additional considerations related to long-term adherence, clinical monitoring, patient education, and ongoing support. 

Conclusion 

As the food immunotherapy field moves toward later-stage development and regulatory evaluation, clearly defined post-treatment outcomes and multi-year follow-up data will be increasingly important for differentiating therapeutic approaches. Such long-term evidence is essential for shaping expectations, guiding programme design, and informing regulatory pathways. 

The three-year follow-up of PRT-120 offers a unique perspective on the durability of protection after oral immunotherapy. These data demonstrate that remission represents a distinct and stable clinical state in which protection is maintained without ongoing dosing. In contrast, desensitisation confers measurable benefit but requires continued daily intake, introducing adherence challenges and an ongoing treatment burden. 

References

1. Bird JA, et al. Long-term safety and immunologic outcomes of daily oral immunotherapy for peanut allergy. J Allergy Clin Immunol Glob. 2023;2(3):100120. 
2. Jones SM, Burks AW, Keet C, et al. Food immunotherapy: pathways to sustained unresponsiveness. J Allergy Clin Immunol. 2020;145(4):1143–1154. 
3. Loke P, Orsini F, Lozinsky AC, 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;6(3):171–184. 
4. Loke P, Wang X, Lloyd M, et al. Two-year post-treatment outcomes following peanut oral immunotherapy in the Probiotic and Peanut Oral Immunotherapy-003 Long-Term (PPOIT-003LT) study. Allergy. 2024;79(10):2759–2774. 
5. DunnGalvin A, Lloyd M, Hsiao KC, Tang MLK, et al. Long-term benefit of probiotic peanut oral immunotherapy on quality of life in a randomized trial. J Allergy Clin Immunol Pract. 2021;9(12):4493–4495.e1. 

About the author 

Professor Mimi Tang, PhD, is a clinician scientist and Director of the Allergy Translation Centre at the Murdoch Children’s Research Institute, where she leads research on the mechanisms of food allergy and clinical approaches that may support more durable immune changes. A specialist in paediatric allergy and immunology with more than 25 years of experience, she has authored over 330 scientific publications and is internationally recognised for her contributions to understanding IgE-mediated disease, oral immunotherapy, and long-term immune outcomes. Professor Tang is also the scientific founder of Prota Therapeutics and provides scientific guidance based on her clinical and translational research expertise.