Date: 2012-11-09
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of data at the 2012 Annual Meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Anaheim, CA.
Company: Teva Pharmaceutical Industries (Israel)
Product: QNASL® (beclomethasone dipropionate)
Action
mechanism: QNASL® is an investigational intranasal corticosteroid in development for the treatment of allergic rhinitis symptoms. The product utilizes the same chemical formulation as QVAR® (beclomethasone dipropionate HFA) Inhalation Aerosol, an inhaled corticosteroid (ICS) approved by the FDA for the maintenance treatment of asthma. QNASL® is administered as a non-aqueous or \"dry” spray delivered by hydrofluoroalkane (HFA), an environmentally friendly propellant.
Disease: seasonal allergic rhinitis (SAR)
Therapeutic area: Allergic diseases - Immune diseases
Country:
Trial details:
Latest
news: * On November 9, 2012, Teva Pharmaceutical Industries has announced additional data from the Phase III clinical program for QNASL® (beclomethasone dipropionate) Nasal Aerosol, highlighting the drug’s efficacy profile in treating children (ages 6-11) with nasal symptoms of seasonal allergic rhinitis (SAR). Additional data also presented at the ACAAI meeting reinforce the long-term ocular safety profile of QNASL® and the functionality and reliability of the device. In a two-week, randomized, double-blind, placebo-controlled study, 715 patients with SAR, aged 6-11 years, received once-daily treatment with QNASL® 80 mcg, 160 mcg or placebo. The primary endpoint, the results for which were previously released1, showed significantly greater (p<0.001) improvement in nasal symptoms compared with placebo for both QNASL® 160 mcg and 80 mcg over the two-week treatment period. Additional data reported further support the efficacy of once-daily dosing with QNASL®. The data show greater (p<0.001) improvements from baseline in patient-reported AM and PM reflective total nasal symptom scores (rTNSS) and patient-reported AM and PM instantaneous total nasal symptom scores (iTNSS) with QNASL® 160 mcg and 80 mcg as compared with placebo (p<0.01). Furthermore, physician-assessed nasal symptom scores (PNSS) show greater improvement in patients receiving QNASL®160 mcg and 80 mcg as compared with placebo (-.096, 95% CI: -1.4, -.05, PHighlights from a study evaluating ocular safety following long-term (52-week) treatment of QNASL® (beclomethasone dipropionate) 320 mcg once-daily were also presented at ACAAI. The primary endpoint, which was previously reported2, showed statistically significant improvements in patient-reported 24-hour rTNSS in patients with PAR, aged 12 years and older, over the first 30 weeks of treatment. Data presented demonstrate that at 30 and 52 weeks, there were no clinically important differences in intraocular pressure (IOP), which refers to the fluid pressure within the eye, between QNASL® and placebo. If IOP increases beyond the normal range of 10-20 mmHg, patients are at an increased risk of developing glaucoma; however, during treatment with QNASL®, IOP remained within normal range (QNASL® is the first nasal aerosol spray to be available with an integrated dose counter that numerically displays every actuation. Evaluations were conducted to assess the accuracy and reliability of the device. To evaluate the safety and efficacy profile of QNASL®, a six-week, randomized, double-blind, placebo-controlled study was conducted in 474 patients with PAR, aged 12 years and older. As previously published in the Allergy & Asthma Proceedings3, the study showed significantly greater improvement in average patient-reported AM and PM rTNSS compared to placebo. Additional data from this study presented at ACAAI demonstrate the performance, functionality and reliability of the integrated dose counter based on daily patient recordings of actuations and dose counter readings. Agreement between subject recordings, measured by a Nasal Device Performance Diary, and dose counter readings was assessed by discrepancies in the following categories: fire not count, count not fire, count unknown fire and count up unknown fire. Of 41,891 subject-reported actuations, only 159 discrepancies were reported in the diary versus the counter. Nearly 80 percent (79.1) of subjects reported 0 discrepancies, 9.4 percent reported only one discrepancy and 6.4 percent reported just two discrepancies. The dose counter had an overall discrepancy rate of 0.38/100 actuations (0.41 [BDP nasal aerosol group]; 0.34 [placebo group] and the discrepancy rate of fire not count was also low (0.09/100 actuations). These results further suggest that the reliable dose counter will help patients track their remaining medication and help to determine when to replace their device. * On March 5, 2012, Teva Pharmaceutical Industries has announced positive findings from four Phase III clinical studies that examined the efficacy and safety profile as well as impact on quality of life of QNASL® (beclomethasone dipropionate) Nasal Aerosol. The data were presented at the 2012 American Academy of Allergy, Asthma and Immunology (AAAAI) Meeting in Orlando, Florida. In a long-term (52-week), double-blind, placebo-controlled, parallel-group study, 529 patients with PAR, aged 12 years and older, were randomized to receive once-daily treatment with QNASL® 320 mcg or placebo. The primary endpoint, the results for which were previously released1, showed a significant (p<0.001) change from baseline weekly averages of the subject reported 24-hour reflective nasal symptom scores (rTNSS) over the first 30 weeks of the treatment period. Additional 52 weeks of treatment data reported further demonstrated the safety and efficacy profile of QNASL® treatment by showing significantly greater improvements from baseline over a 24-hour period in both rTNSS (-1.09 [95% CI: -1.6, -0.6], p<0.001) and instantaneous nasal symptom scores (iTNSS) (-1.10 [95% CI: -1.6, -0.6]; p<0.001) compared with placebo. Furthermore, greater improvements in individual nasal symptoms (nasal congestion, nasal itching, rhinorrhea and sneezing) were also demonstrated in the QNASL® group compared to placebo. QNASL® was generally well tolerated with a safety profile similar to placebo with the exception of epistaxis, which occurred more frequently with the active treatment. The most commonly reported adverse events (5% or more subjects) were nasopharyngitis, epistaxis, upper respiratory tract infection, sinusitis and headache. Treatment difference in the average AM and PM subject-reported rTNSS over the first 6-week treatment period from the same study were also reported. The LS mean treatment difference between QNASL® 320 mcg/day and placebo was –0.78 (95% CI: -1.2, -0.5) (p<0.001). As a result of the bothersome symptoms associated with allergic rhinitis (AR), patient quality of life can also be affected. Results from a 6-week, double-blind, placebo-controlled, parallel-group study of patients with PAR (N=474) demonstrated that QNASL® significantly improved quality of life compared with placebo (-0.58 [95% CI: -0.9, -0.2]; p=0.001), as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Improvements from baseline were greater with QNASL®for all seven individual domains of the RQLQ. Physician-reported nasal symptom scores were also significantly improved (-1.22 [95% CI: -1.7, -0.7]; p<0.001). The primary endpoint of change from baseline of average AM and PM subject-reported rTNSS was also significant (p<0.001), which was reported previously in 2011. To evaluate the safety of QNASL®, a double-blind placebo and active controlled parallel-group study was conducted to determine the effect of 6 weeks of therapy with QNASL® on hypothalamic-pituitary adrenal axis function (HPA-axis) in adult and adolescent patients. As previously reported, treatment with QNASL® at a dose of 320 mcg/day was not associated with HPA-axis suppression in adult and adolescent subjects with PAR, as demonstrated by the geometric mean ratio for QNASL® 320 mcg/day to placebo (0.96 (95% CI: 0.87, 1.06).3 However, HPA-axis function suppression is known to have an impact on growth in adolescent subjects. Therefore, a subgroup analysis of 25 adolescents from the same study, randomized to treatment with QNASL® 320 mcg/day, placebo or an active control of prednisone 10 mg/day showed that, after 6 weeks, the geometric mean serum cortisol weighted value in patients treated with QNASL® was similar to those treated with placebo (0.92 [95% CI: 0.72, 1.16]), but treatment with active control oral prednisone resulted in significant suppression of serum cortisol levels – the placebo to prednisone mean serum cortisol weighted value [2.56 [95% CI: 1.76, 3.71]). These results further support the lack of HPA-axis suppression with QNASLTM treatment reported previously. Finally, new results from a 2-week, randomized, double-blind, placebo-controlled study in 715 children (6-11 years of age) with SAR were also presented for the first time at AAAAI. The study sought to measure the average morning and evening rTNSS with once-daily treatment with QNASL® at a dosage of 80 mcg or 160 mcg, as well as the safety profile compared to placebo. Improvements in both AM and PM rTNSS were significantly greater for those treated with QNASL®80 mcg (-0.71 [95% CI: -1.1, -0.3) and 160 mcg (-0.76 [95% CI: -1.1, -0.4) compared to placebo. The safety profile of QNASL® was also similar to placebo. The most commonly reported adverse events for either treatment group were epistaxis and headache. *On August 5, 2011, the FDA accepted for review the New Drug Application (NDA) filing for QNASL®. The submission was based on a comprehensive clinical development program consisting of four Phase III clinical trials designed to evaluate the safety and efficacy of QNASL®for the treatment of SAR and PAR symptoms.
QNASL® has been approved by the FDA on March 23, 2012. The product became available to patients by prescription in April 2012, making it the first marketed nonaqueous or “dry” nasal aerosol product in a category that reports annual sales of $2.5 billion.4 QNASL® is delivered as a once-daily, nonaqueous aerosol that uses an environmentally friendly5 propellant (HFA) and contains a built-in dose counter.
