FDAnews Drug Daily Bulletin

CBER Adcomm Offers Grim Outlook on Allergen Immunotherapy Clinical Trials

Jan. 29, 2016

CBER’s Allergenic Products Advisory Committee gave a less than stellar assessment on the outlook of clinical trials for immunotherapies to treat food allergies.

Committee members had more questions than answers during a meeting last week about companies’ development plans for allergen immunotherapies, which aim to induce a state of desensitization in food-allergic patients to prevent catastrophic responses following exposure.

For example, the primary endpoint in AIT studies is usually the degree of desensitization in the treatment cohort compared with the placebo group. However, tolerance — the complete and permanent resolution of clinical response following exposure to an allergen — has yet to be achieved in any controlled trial. There are consequently no licensed AITs.

Several members agreed that the goal of total cure was simply too high of a bar. Studies should aim to combat the risk of life-threatening reactions from accidental exposures rather than demonstrating complete tolerance, they said.

Concerns also were raised about adverse reactions from the large pediatric population, particularly in infants and children under 5. For one, it could be difficult to detect a reaction from children who may not be able to verbalize their symptoms. Some members proposed age limits for participation in such trials to avoid such ambiguity.

Moreover, there were questions about the starting and stopping points. What should be the criteria and approach for somebody involved in a clinical trial who is extremely sensitive to an allergen? What should the threshold be for identifying the eliciting dose of an allergen?

Esophagitis was another issue raised, as there has been anecdotal data of children in immunotherapy trials developing the condition. But members noted that there needs to be a review of hard data to determine if children in these trials are more likely to develop the disease than their peers.