QNASLTM Phase III Data Indicate Investigational Therapy with New Mode of Delivery has Positive Safety and Effective Profile in Treatment of Seasonal and Perennial Allergic Rhinitis

QNASLTM Phase III Data Indicate Investigational Therapy with New Mode of Delivery has Positive Safety and Effective Profile in Treatment of Seasonal and Perennial Allergic Rhinitis

Late Stage Data Demonstrated Long-Term Nasal Symptom Relief and Improvement in Quality of Life
2012 AAAAI Annual Meeting
JERUSALEM--(BUSINESS WIRE)--Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) today announced positive findings from four Phase III clinical studies that examined the efficacy and safety profile as well as impact on quality of life (QoL) of QNASLTM (beclomethasone dipropionate [BDP]) Nasal Aerosol. QNASLTM is a non-aqueous, "dry" nasal aerosol corticosteroid in development for the treatment of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). The data were presented today at the 2012 American Academy of Allergy, Asthma and Immunology (AAAAI) Meeting in Orlando, Florida.

    "Based on the timing of the NDA acceptance and standard review timelines, we anticipate receiving FDA feedback on the approval status of QNASL in the near future."

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 QNASLTM 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 today further demonstrated the safety and efficacy profile of QNASLTM 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 QNASLTM group compared to placebo. QNASLTM 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 QNASLTM 320 mcg/day and placebo was –0.78 (95% CI: -1.2, -0.5) (p<0.001).

"The long term data validated the efficacy and safety profile of QNASL and demonstrated positive results experienced by patients using the new 'dry' aerosol delivery," said Gary N. Gross, MD, FACAAI, practicing allergist and co-founder of the Dallas Asthma and Allergy Center. "Since allergic rhinitis is one of the most common allergic diseases in the U.S., affecting more than one in five people, it's important for there to be a variety of treatment options available to patients experiencing ongoing challenges with the condition."
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 QNASLTM 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 QNASLTM 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 2011.2

To evaluate the safety of QNASLTM, a double-blind placebo and active controlled parallel-group study was conducted to determine the effect of 6 weeks of therapy with QNASLTM on hypothalamic-pituitary adrenal axis function (HPA-axis) in adult and adolescent patients. As previously reported, treatment with QNASLTM 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 QNASLTM 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 QNASLTM 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 QNASLTM 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.3
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 QNASLTM 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 QNASLTM 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 QNASLTM was also similar to placebo. The most commonly reported adverse events for either treatment group were epistaxis and headache.

On August 5, 2011, the United States (U.S.) Food and Drug Administration (FDA) accepted for review the New Drug Application (NDA) filing for QNASLTM. 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 QNASLTM for the treatment of SAR and PAR symptoms.

"Teva Respiratory is committed to the 20 percent of adults and adolescents suffering from allergic rhinitis in the U.S. and is hopeful that, if approved, QNASL will serve as a positive solution that helps allergy sufferers address and treat the bothersome symptoms of allergies," said Tushar Shah, MD, Senior Vice President, Teva Global Respiratory Research and Development. "Based on the timing of the NDA acceptance and standard review timelines, we anticipate receiving FDA feedback on the approval status of QNASL in the near future."

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