The process of identifying and bringing to market novel therapies is extremely challenging and notoriously expensive as most drug candidates fail. In the respiratory area, like in other areas, improving the success rate of new therapeutic entities is one of the industry’s greatest challenges. To do so, the use of reliable methodologies providing sensitive, reproducible, and detailed outcomes predictive of clinical success is key in guiding the strategic decision-making process.
TRUSTED OUTCOMES. INDUSTRY STANDARD.
The flexiVent has proven to be an invaluable tool in early drug development. Over the years, it has become the industry standard in terms of preclinical lung function measurements, as evidenced by an ever growing number of related scientific publications and patents. The flexiVent’s exhaustive set of highly reproducible measurements offers outcomes that can be trusted at any point during the preclinical drug development process. The detailed measurements help gather deep insights into respiratory mechanisms early on in the process, preventing additional development costs.
- SCIREQ Application Note: The flexiVent in the Asthma Drug Development Process
- List of drug-related patents citing the flexiVent
- Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics – Walker et al. Front. Physio. 3:491. doi: 10.3389/fphys.2012.00491
- Vaccination against IL-33 inhibits airway hyperresponsiveness and inflammation in a house dust mite model of asthma – Lei et al. PLoS one 10: e0133774, 2015
- Evaluation of lung function and lung fibrosis in mouse models of interstitial lung disease – Dinocca et al. Am J Respir Crit Care Med 191: A3453, 2015
- IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways – Kearley et al. Am J Respir Crit Care Med 183: 865-875, 2011
REPRODUCIBLE INTERVENTION. PREDICTIVE OUTCOMES.
The administration of drugs or novel therapeutic carriers through the lung could be desirable for many reasons. The large surface area and high vascularization of the lung can provide a fast and effective delivery of substances either locally or systemically, via the blood. When considering inhalation as the route for drug delivery, SCIREQ’s intervention platform, the inExpose, offers a significant positive impact on study reproducibility and research efficiency by ensuring process standardization. Integrated with the Aeroneb nebulizer, the inExpose provides sophisticated computer control which enables automated, precise, and repeatable aerosol exposure sessions to small laboratory animals. Furthermore, the inExpose offers small internal volumes, reducing exposure ramp-up times and minimizing the need for large quantities of material.
- SCIREQ Application Note 013: Reproducible Respiratory Research
- Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers – Patlolla et al. J Control Release. 144: 233-241, 2010
- Pharmaceutical composition of oxidised avidin suitable for inhalation – De Santis. U.S. patent application 14/236,445, 2014
- Inhaled fluticasone propionate impairs pulmonary clearance of Klebsiella pneumoniae in mice – Patterson et al. Respir. Res. 13: 40, 2012
- Nebulized anti-IL-13 monoclonal antibody Fab’ fragment reduces allergen-induced asthma – Hacha et al. Am J Respir Cell Mol Biol. 47: 709-717, 2012
CONCIOUS MEASUREMENTS. SPONTANEOUS BREATHING.
Respiratory function can be assessed by a number of techniques. Measurements in conscious subjects can be done using various plethysmography techniques such as unrestrained whole body plethysmography (WBP), double chamber plethysmography (DCP), or head-out plethysmography (HOP). While these measurement methods offer the benefit of having the subjects closer to their natural state, uninfluenced by anaesthetic side effects, the trade-off is a lower measurement accuracy and precision.
NON-INVASIVE TRANSLATIONAL MEASUREMENTS.
One proposed approach to lower the failure rate of novel therapies is to incorporate translational outcomes early-on in the drug development process. In large animal species (Beagle dogs, non-human primates), the airwave oscillometry technique, provided by the tremoFlo system, offers a non-invasive assessment of novel therapies’ effects. This is based on ventilatory parameters (tidal volume, respiratory rate) and a frequency-dependent assessment of the mechanical properties of the respiratory system (resistance, reactance). This technique is also employed in a clinical setting to assess patients thus providing a translational outcome utilized across all phases of drug trials.
A comprehensive overview of the pharmacological properties of novel therapies is required to best identify the candidates to move forward in the drug development process. This can be achieved through a range of techniques which includes the classical isolated tissue bath, where external influences can be removed.
- Airway smooth muscle in the pathophysiology and treatment of asthma – Doeing et al. J Appl Physiol 114:834-843, 2013
- Measurement of smooth muscle function in the isolated tissue bath – applications to pharmacology research – Jespersen et al. J Vis Exp 95: e52324, 2015
- Increased contractility of isolated lung parenchyma in an animal model of pulmonary fibrosis – Evan et al. Am Rev Respir Dis 125: 89-94, 1982