Vectura Group plc has announced the publication in the European Respiratory Journal (ERJ) of a clinical study demonstrating positive results from its Phase IIb/III (Acti-AICS-001) clinical trial investigating the efficacy, safety and tolerability of VR475 in the treatment of oral corticosteroid (OCS)-dependent (GINA Step 5) asthma patients.
VR475 is an investigational drug/device combination product that delivers an approved corticosteroid, budesonide, to the lungs via Vectura’s AKITA Jet inhalation system, controlled by a Smart Card. The system is designed to deliver budesonide to the small airways of the lungs more efficiently than conventional delivery systems.
The study compared the effects of two doses of budesonide delivered by AKITA? Jet inhalation system (AICS-BUD 1 mg and AICS-BUD 0.5 mg) with placebo and budesonide delivered by conventional nebuliser (CN-BUD 1 mg). These treatments were added to standard severe asthma therapies for 18 weeks. Main study findings include:
- Significantly more patients successfully reducing OCS dose by more than 50% whilst maintaining asthma stability compared with placebo (primary endpoint; AICS-BUD 1 mg 80% vs placebo 63%; p=0.02)
- Mean reduction in OCS dose was 7.1 mg for AICS Bud 1 mg and 3.6 mg for placebo; p=0.005
- Improved lung function for both AICS-BUD doses but not placebo or CN-BUD 1 mg (FEV1 improvement from baseline to week 18: AICS-Bud 1 mg (239 mL; p<0.001); AICS-Bud 0.5 mg (126 mL; p=0.01), placebo (93 mL; p=0.36); CN-Bud (137 mL; p=0.18)
- Fewer patients experienced asthma exacerbations in the AICS-BUD 1 mg treated group (AICS-BUD 1 mg, 7.5%) compared with placebo (17.5%) and CN-BUD 1 mg group (22.5%)
- Significantly fewer days were spent in hospital in relation to total study duration in the AICS-Bud 1 mg arm (5 of 13,152 patient treatment days vs placebo (49 of 6,328 days), p<0.001)
All treatments were well tolerated.
VR475 resulted in significant and meaningful OCS reduction in OCS-dependent asthma patients while improving pulmonary function and maintaining asthma exacerbation control.
Dr. Gerhard Scheuch, Chief Scientific Officer of Vectura:
“Our FAVORITE inhalation approach, on which this therapy is based, has clearly demonstrated its potential for treating severe asthma. FAVORITE ensures precise and uniform drug targeting, higher deposition in the lungs and significant reduction in dose variability through guided inhalation. A further clinical trial is planned for the first half of 2015 to confirm this potential. There is a clear need for better treatments for patients with severe, uncontrolled asthma. Current treatments such as OCS are associated with unwanted side effects and with significant mortality and morbidity, as well as a large proportion of the costs associated with asthma treatment.”
199 patients (18-65 years) with OCS-dependent asthma were randomised (2:1:1:1) to 18-week, twice daily, double-blind treatment with AICS (AKITA inhaled corticosteroid)-Bud 1 mg, AICS Bud 0.5 mg, AICS-placebo, or open-label Bud 1 mg administered by conventional nebuliser (CN-Bud). OCS doses were tapered until week 14. The study was conducted in Germany, Poland and Ukraine.
About VR475: VR475 is an investigational drug/device combination product that comprises the inhaled corticosteroid budesonide, delivered using Vectura’s smart inhalation system, the AKITA Jet, incorporating FAVORITE technology. It is used to deliver budesonide more efficiently to the small airways of the lungs compared with conventional nebulisers. The AKITA Jet inhalation system includes a Smart Card technology to program the device with the patient’s optimal breathing pattern. This ensures targeted delivery of the drug to the lungs as well as being able to detect patient’s compliance.
About FAVORITE (Flow and Volume Regulated Inhalation TEchnology)
The patient’s breathing pattern can alter the efficiency of drug delivery to different parts of the lungs. Control of the inspiratory flow rate, the inspiratory volume of aerosol and the timing during the inspiration when the drug aerosol is delivered, can materially affect how much drug gets to central or peripheral parts of the lungs. This is the basis of our proprietary, smart nebulisation-based technology known as FAVORITE.
This control is achieved through a modified inhalation system that delivers the nebulised airstream tailored to the individual patient’s breathing capacity. The increased efficiency of delivery means the drug is distributed more effectively, allowing targeted deposition in the lungs. Other benefits for the patient may also be derived from this approach, such as shorter treatment time.
About severe Asthma
Asthma is a chronic disease of the conducting airways in which inflammation is associated with reversible airflow limitation and bronchial reactivity. The mainstays of chronic asthma treatment are the ?-agonists (to treat bronchoconstriction), used either alone or in combination with anti-inflammatory drugs such as corticosteroids. Severe asthma, uncontrolled by inhaled beta agonists and steroids has limited further treatment options, one of which is the use of oral corticosteroids. Chronic oral therapy with corticosteroids is commonly associated with significant side effects including: truncal obesity, hypertension, glaucoma, glucose intolerance, acceleration of cataract formation, bone mineral loss, psychological effects, growth suppression in children and adrenal suppression. Asthma exacerbations are linked with significant mortality and morbidity as well as being associated with a significant proportion of the cost of asthma treatment and care.
Nebulised budesonide using a novel device in patients with oral steroid-dependent asthma, Claus Vogelmeier, Peter Kardos, Thomas Hofmann, Sebastian Canisius, Gerhard Scheuch, Bernhard Muellinger, Karlheinz Nocker, Guenter Menz and Klaus F. Rabe, European Respiratory Journal, doi: 10.1183/09031936.00152014, published 10 December 2014.