The 2018 Joint Congress of the American Academy of Allergy, Asthma and Immunology (AAAAI) and World Allergy Organization (WAO) has been buzzing with excitement over Aimmune Therapeutics and the eye-opening efficacy data achieved in their Phase III PALISADE trial for peanut oral immunotherapy drug candidate, AR-101.
While minimal new data were presented in the official conference proceedings on Sunday afternoon, the 90-minute analyst and investor event that followed in the evening was rich with compelling new details. GlobalData believes that these data further solidify the efficacy of AR-101 in the mitigation of peanut allergy and begin to paint a clearer picture of what oral immunotherapy with AR-101 might look like in the real world.
PALISADE trial results
Though the majority of patients studied in the PALISADE trial were between four and 17 years of age (N=496), a small portion were adults aged 18-55 (N=58). Age did not appear to prevent patients from having a positive response to oral immunotherapy.
Adult patients that completed the full course of treatment with AR-101 boasted a response rate similar to that of children—about 85%. It is important to note that the drop-out rate was exceptionally high in this age group, with only 57% (N=33) completing the trial. Though no specific breakdown of reasons for discontinuation was provided, the blame was squarely placed on non-treatment-related issues such as scheduling problems and missed appointments.
While the 18-55 age range seems like a promising future target for oral immunotherapy with AR-101, further research into adapting the treatment protocol to fit the needs of this age group—especially college-age adults—is required. What these data might mean for the age recommendations put on the label for the product remains to be seen.
Another key set of data demonstrated the striking differences in symptom severity in AR-101 and placebo-treated patients at the exit double-blind, placebo-controlled food challenge (DBPCFC). Overall, AR-101-treated patients had an overwhelmingly lower frequency of moderate and severe symptoms compared to their placebo-treated counterparts.
In fact, only 12 out of 116 patients in the placebo group were eligible to attempt the primary endpoint dose of 600 mg—the other 104 were excluded due to moderate symptoms at lower doses. The need for epinephrine administration was also drastically different between the placebo and treatment groups: 9% of AR-101-treated patients required one or more administrations of epinephrine, in comparison to 53% of placebo-treated patients.
Decreasing ratio of immunoglobulins
New data presented at the conference also touched on some intriguing changes to immunological parameters throughout treatment with AR-101. Of particular note was the ratio of peanut-specific IgE/IgG4. It is a common clinical finding during immunotherapy for allergen-specific IgE to decline, while allergen-specific IgG4 increases.
This makes an overall decrease in the ratio of the two immunoglobulins a potential sign of progress. For AR-101-treated patients, the ratio dropped dramatically during the up-dosing period (to about a quarter of the baseline value) and continued to fall further during the maintenance period (to about a tenth of the baseline value.) For placebo-treated patients, the peanut-specific IgE/IgG4 ratio remained the same throughout the entire study.
Aimmune remained straightforward about the safety of the product—there were some unpleasant reactions and these resulted in a 12.4% drop-out rate. However, the company stressed that these allergic symptoms are an expected part of the desensitization process and that for most patients, the symptoms diminish over time with maintenance dosing. Ultimately, oral immunotherapy with AR-101 may not be for everyone, but patients who are motivated enough to invest the time and effort will likely be very satisfied.