Regulatory Decision Summary for Dymista

The current indications for Dymista, a combination intranasal corticosteroid (fluticasone propionate) plus antihistamine (azelastine hydrochloride), specify that it is to be used for “the symptomatic treatment of moderate to severe seasonal allergic rhinitis (SAR) and associated ocular symptoms in adults, adolescents, and children aged 6 years and older for whom monotherapy with either antihistamines or intranasal corticosteroids is not considered sufficient”. The sponsor has provided various rationale to support removing the requirement that monotherapy treatment must first be considered as insufficient prior to prescribing Dymista.

The sponsor’s rationale for the revised indications was based on a combination of published literature, updated guidance documents, and post-marketing data, in addition to efficacy and safety data from Phase 3 studies provided in prior submissions. No new clinical trial data was provided based on the fact that any new clinical trials performed to justify the revised indication would not differ substantively from the Phase 3 trials already provided in prior submissions. The previously reviewed Phase 3 studies included patients with moderate to severe SAR who were effectively using the study medication as a first-line therapy. There was no requirement in these studies that patients must have been inadequately treated by prior monotherapy treatments. Previously provided clinical trials contain efficacy and safety data sufficient to support the proposed indication for the current submission. 

The rationale for initially restricting the indications to include only patients for whom monotherapy treatment is not considered sufficient was based on the principle of minimizing unnecessary drug exposure. Several published studies provided evidence that allergic rhinitis patients commonly treat their symptoms as needed, and often switch between medications or use multiple medications together in order to achieve symptom control. The tendency to switch or combine medications is related to the fact that no approved SAR medication has a high rate of treatment success. However, compared head-to-head, Dymista has been demonstrated in controlled Phase 3 clinical studies to provide a significantly improved treatment benefit relative to its corticosteroid and antihistamine monocomponents. Compared to intranasal corticosteroids (which are regarded as the gold standard monotherapy for SAR), Dymista also has a significantly faster onset of action. Use of the most efficacious medication as an initial treatment improves the chances of treatment success, and can reduce the need for the use of additional drugs. Thus, current evidence does not support the likelihood that use of Dymista will increase overall drug exposure.

Regarding safety, serious side effects potentially encountered with the use of Dymista are related to the corticosteroid component (for example glaucoma and cataracts), and are considered to be very rare. The addition of the antihistamine component adds only the risk of occurrence of bitter taste (which occurred in 4.1% of patients in a pooled analysis from Phase 3 studies).

In recognition of the benefit of Dymista relative to other available treatment options, and its favorable safety profile, published treatment guidelines have been updated in recent years to recommend use of an intranasal corticosteroid with or without a combined intranasal antihistamine as a first line treatment for allergic rhinitis. Overall, the treatment benefits for Dymista continue to outweigh the risks with the proposed revision to the indications.