Asthma (Pediatric)

November 28, 2016

AstraZeneca released results of a phase III study of Symbicort (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol 80/4.5 in pediatric patients between 6 to <12 years of age with asthma. The global, multicenter, 12-week, randomized, double-blind, parallel-group CHASE 3 trial evaluated the efficacy and safety of budesonide/formoterol in a pressurized metered dose inhaler (pMDI) 80/2.25 micrograms, and Symbicort (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol pMDI 80/4.5 micrograms, compared with budesonide pMDI 80 micrograms, all given two inhalations twice-daily. The study randomized 279 children 6 to <12 years of age, from which 273 received treatment, and involved a total of 88 study centers located in four countries. The study results showed changes from baseline at week 12 in one-hour post-dose FEV1 and 15-minute post-dose FEV1 were significantly greater with Symbicort 80/4.5 micrograms two inhalations twice daily versus budesonide 80 micrograms two inhalations twice daily (both p=0.015), but not budesonide/formoterol 80/2.25 micrograms two inhalations twice daily versus budesonide 80 micrograms two inhalations twice daily. The change from baseline in one-hour post-dose PEF (peak expiratory flow) was superior at week 12 with Symbicort 80/4.5 micrograms versus other treatments (p<0.05). There were no notable differences in safety profiles between either of the budesonide/formoterol doses and budesonide or between the two budesonide/formoterol doses. Among the most common adverse events, upper respiratory tract infection, pharyngitis, headache and vomiting were more frequent, with budesonide/formoterol doses compared to the budesonide 80 micrograms dose. The CHASE 3 results were submitted to the FDA and other health authorities in accordance with regulatory requirements.

September 12, 2016

AstraZeneca reported results of a phase II study of adding benralizumab to the standard-of-care for severe asthma. The WINDWARD program in asthma is made up of six phase III trials, including SIROCCO, CALIMA, ZONDA, BISE, BORA and GREGALE. WINDWARD evaluated a total of 3,068 patients in 798 sites across 26 countries. The two pivotal trials, SIROCCO and CALIMA, are randomized, double-blind, parallel-group, placebo-controlled trials designed to evaluate the efficacy and safety of a regular, subcutaneous administration of benralizumab (fixed 30mg dose) for up to 56 weeks in exacerbation-prone adult and adolescent patients 12 years of age and older. A total of 2,511 patients (1,205 in SIROCCO and 1,306 in CALIMA) currently receiving standard-of-care medicine (including high-dosage inhaled corticosteroids and long-acting beta 2 agonists [ICS/LABA]) were randomized globally and received either benralizumab 30mg every four weeks; benralizumab 30mg every four weeks for the first three doses followed by 30mg every eight weeks; or placebo. All benralizumab doses were administered via subcutaneous injection using an accessorized pre-filled syringe. The SIROCCO and CALIMA trials evaluated the effect of two dosing regimens of benralizumab 30mg administered in four-week and eight-week regimens as add-on therapy to standard-of-care medicine across primary and key secondary endpoints. Results showed reductions in the annual rate of asthma exacerbations (up to 51%); improvement in lung function (change in FEV1 of up to 159 mL), which was seen at four weeks after the first benralizumab dose and sustained throughout the treatment period; improvement in asthma symptoms, such as wheeze, cough, chest tightness and shortness of breath. The data from the SIROCCO and CALIMA trials will be included in regulatory submissions for benralizumab that are planned for the U.S. and EU later in 2016.

May 2, 2016

ALK issued results of a phase III trial of Acarizax for house dust mite (HDM) allergic asthma. The randomized, double-blind, placebo-controlled trial enrolled 834 adult patients. The trial was conducted at 109 sites in 13 European countries and forms part of ALK’s ongoing clinical development program for Acarizax, which has recently been approved in 11 European countries and where it is currently being launched. Patients were treated daily with either a 12 SQ-HDM or a 6 SQ-HDM dose, or with placebo in addition to inhaled corticosteroids (ICS) and short-acting beta-agonists (SABA). After a period of treatment varying between seven and 12 months, daily ICS use was reduced by half for three months and subsequently withdrawn completely for another three months for patients who did not experience an asthma exacerbation. The trial showed that 12 SQ-HDM (the dose approved in the E.U.) significantly reduced the risk of a moderate or severe asthma exacerbation relative to placebo with a hazard ratio (HR) of 0.66, corresponding to a 34% risk reduction. This included a 36% reduction in risk of nocturnal awakening or increase in daily symptoms (HR: 0.64); a 48% reduction in the risk of increased use of SABA treatments (HR: 0.52); and a 42% reduction in the deterioration of lung function (HR: 0.58).