Veramyst is a nasal spray containing an aqueous suspension of micronized fluticasone furoate. Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. The precise mechanism of action on rhinitis symptoms is not known.

Veramyst is specifically indicated for the treatment of the symptoms of seasonal and perennial allergic rhinitis in patients 2 years of age and older.

Veramyst is supplied as a suspension for intranasal administration via a spray pump. The recommended initial dose of the drug for adults and adolescents 12 years of age and older is 110 mcg once daily administered as 2 sprays (27.5 mcg/spray) in each nostril. This should be titrated to the minimum effective dose to reduce the possibility of side effects. When the maximum benefit has been achieved and symptoms have been controlled, reducing the dosage to I spray (55 mcg/spray) in each nostril) once daily may be effective in maintaining control of allergic rhinitis symptoms. The recommended initial dose of the drug in children 2 to 11 years of age is 55 mcg once daily administered as 1 spray (27.5 mcg/spray) in each nostril. Children not adequately responding to 55 mcg may use 110 mcg (2 sprays in each nostril) once daily. Once symptoms have been controlled, the dosage may be decreased to 55 mcg once daily.

FDA Approval
FDA approval of Veramyst for adult and adolescent subjects was based on the results of five clinical trials. These randomized, double-blind, parallel-group, multicenter, placebo-controlled trials 1,829 subjects aged 12 and older. The five trials included one 2-week dose-ranging trial in subjects with seasonal allergic rhinitis, three 2-week confirmatory efficacy trials in subjects with seasonal allergic rhinitis, and one 4-week efficacy trial in subjects with perennial allergic rhinitis. Of the 1,829 subjects, 722 received Veramyst 110 mcg once daily administered as two sprays in each nostril. The primary endpoint was efficacy based on total nasal symptom score (TNSS). This was calculated as the sum of the patients’ scoring of the 4 individual nasal symptoms (rhinorrhea, nasal congestion, sneezing, and nasal itching) on a 0 to 3 categorical severity scale (0 = absent to 3 = severe). These were scored as reflective (rTNSS); symptom severity over the previous 12 hours and instantaneous TNSS (iTNSS); symptom severity at the time immediately prior to the next dose. Secondary endpoints included total ocular symptom score (TOSS) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as reflective or instantaneous scores. Results are as follows:

Dose Ranging Trial
This trial evaluated the efficacy of 4 dosages of fluticasone furoate nasal spray (440, 220, 110, and 55 mcg) in subjects with seasonal allergic rhinitis. Each of the 4 doses demonstrated statistically significant greater decreases in the rTNSS than placebo (p=<0.001). The spray also demonstrated greater decreases in AM iTNSS than placebo, and the difference between each of the 4 fluticasone furoate treatment groups and placebo was statistically significant (p=<0.001), indicating that the effect was maintained over the 24-hour dosing interval.

Seasonal Allergic Rhinitis Trials
These three trials were designed to evaluate 110 mcg of fluticasone furoate once daily compared with placebo in subjects with seasonal allergic rhinitis over a 2-week treatment period. In all three trials Veramyst demonstrated a statistically significant greater decrease from baseline in the rTNSS and AM iTNSS compared to placebo. In terms of ocular symptoms, in all three trials Veramyst demonstrated a statistically significant greater decrease from baseline in the rTOSS than placebo. A statistically significant decrease from baseline in the overall RQLQ than placebo was observed as well. The overall RQLQ score mean change from baseline between the groups treated with Veramyst and placebo ranged from -0.60 to -0.70.

Perennial Allergic Rhinitis Trials
This trial was designed to evaluate fluticasone furoate 110 mcg once daily compared to placebo in subjects with perennial allergic rhinitis over a 4-week treatment period. Veramyst demonstrated a statistically significant decrease from baseline in the rTNSS and AM iTNSS than placebo and this improvement persisted for 24 hours. However, statistical significance was not seen in improvement from baseline in total ocular symptom scores (rTOSS) or in disease-specific quality of life as measured by the RQLQ when compared to placebo. The overall RQLQ score mean change from baseline difference between the Veramyst group and the placebo group was -0.23, which did not meet the minimally important difference of =0.5.

FDA approval for Veramyst in pediatric patients aged 2 to 11 was based on two clinical trials. These controlled trials enrolled a total of 1,112 subjects with seasonal or perennial allergic rhinitis. Subjects received 55 or 110 mcg once daily for 2 to 12 weeks. The trial designs were similar as those for adult and adolescent subjects however, efficacy determination was made from patient- or parent/guardian-reported TNSS for children aged 6 to <12 years. In seasonal allergic rhinitis, the difference in rTNSS was statistically significant only for the 110-mcg dose. In perennial allergic rhinitis, the difference in rTNSS was statistically significant only for the 55 mcg dose. Changes in ocular symptoms scores (rTOSS) in the seasonal allergic rhinitis trial were not statistically significant compared with placebo for either dose. rTOSS was not assessed in the perennial allergic rhinitis trial.

Ongoing Study Commitments

• GlaxoSmithKline has agreed to conduct a one-year linear growth study in children with fluticasone furoate using a dose that is relevant to the proposed fluticasone furoate nasal spray dose in children. A linear growth study conducted with a formulation other than the nasal formulation may be adequate provided the systemic exposure from that formulation is higher than the systemic exposure from the nasal formulation. Submit a labeling supplement reflecting the results of the study.
  Protocol Submission: August 2007
  Study Start: November 2007
  Final Report Submisison: November 2011
• GlaxoSmithKline has agreed to conduct a 2-year safety study to assess the long-term effects of fluticasone furoate nasal spray on ocular safety, including cataract formation and the development of elevated intraocular pressure/glaucoma. Submit a labeling supplement reflecting the results of the study.
  Protocol Submission: October 2007
  Study Start: January 2008
  Final Report Submission: February 2011

Adverse events associated with the use of Veramyst in adult and adolescent patients may include, but are not limited to, the following:

• Headache
• Epistaxis
• Pharynolaryngeal pain
• Nasal ulceration
• Back pain

Adverse events associated with the use of Veramyst in pediatric patients may include, but are not limited to, the following:

• Headache
• Nasopharyngitis
• Epistaxis
• Pyrexia
• Pharynolaryngeal pain
• Cough

In addition, Veramyst may result in the development of glaucoma and/or cataracts. Veramyst is a corticosteroid and thus should be used with caution in patients with immunosuppressive infections because of the potential for worsening of these infections. Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients, hence the growth of pediatrics using Veramyst should be closely monitored.

Veramyst is a nasal spray containing an aqueous suspension of micronized fluticasone furoate. Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. The precise mechanism of action on rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. Specific effects of fluticasone furoate demonstrated in in vitro and in vivo models included activation of the glucocorticoid response element, inhibition of pro-inflammatory transcription factors such as NFkB, and inhibition of antigen-induced lung eosinophilia in sensitized rats.

Martin BG, Ratner PH, Hampel FC, Andrews CP, Toler T, Wu W, Faris MA, Philpot EE Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents. Allergy and asthma proceedings : the official journal of regional and state allergy societies 2007 Mar-Apr;28(2):216-25

Kaiser HB, Naclerio RM, Given J, Toler TN, Ellsworth A, Philpot EE. Fluticasone furoate nasal spray: A single treatment option for the symptoms of seasonal allergic rhinitis. The Journal of allergy and clinical immunology 2007 Apr 4

Mandl M, Nolop K, Lutsky BN. Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. The 194-079 Study Group. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 1997 Sep;79(3):237-45

For additional information regarding Veramyst or seasonal and perennial allergic rhinitis, please visit the Veramyst web page.