The run of good news continues for AusBiotech member Pharmaxis (ASX:PXS) with the Sydney-based company announcing positive results from its recently completed Phase 2 trial of BRONCHITOL (mannitol) in children and adolescents with cystic fibrosis.
The trial, conducted across 39 global centres, met its primary endpoint and confirms the PBS-listed therapy is efficacious in young patients, regardless of concomitant dornase alfa use.
BRONCHITOL is approved in Europe. It was not approved in the US but the company is conducting a new Phase 3 clinical trial of the therapy in accordance with requirements set by the FDA in order for BRONCHITOL to be approved in the US.
BRONCHITOL is a precision spray‐dried form of mannitol, delivered to the lungs by a specially designed, portable inhaler.
The company has undergone a virtual rebirth recently, highlighted by an agreement with Boehringer Ingelheim for the development of compound PXS‐4728A as a treatment for cardiometabolic diseases such as Non-Alcoholic Steatohepatitis.
The completed Phase 2 trial (CF204) was a crossover design with patients aged 6 to 17 years receiving either 400mg of BRONCHITOL or a placebo twice a day for eight weeks on top of standard of care before a washout period of eight weeks followed by a further eight weeks on the alternate treatment.
According to the company, during the BRONCHITOL treatment period patients had a statistically significant improvement in lung function compared to placebo showing an absolute improvement of 3.42 per cent in FEV, which equates to a relative change in FEV of 4.97 per cent.
This treatment improvement in the primary endpoint occurred irrespective of whether patients were taking dornase alfa, said the company.
Secondary endpoints in the trial included absolute change in FEF, which Pharmaxis said is thought to have particular significance in younger patients.
BRONCHITOL produced an absolute improvement of 5.75 per cent in FEF equating to a relative improvement of 10.5 per cent. In other secondary endpoints, treatment induced sputum weight was significantly increased and a positive trend was seen in FVC. Although not recorded as an endpoint, patients on BRONCHITOL experienced approximately 25 per cent fewer lung infections and exacerbations of cystic fibrosis which is supportive of the improvements seen in earlier studies despite the short duration of this study.
“These clinical trial results are very pleasing. The positive results were seen in a group of patients with a range of genetic subtypes and reinforce the view that Bronchitol has a clear place in the treatment of CF," said Mr Phillips.
“The trial utilised a number of different design features to overcome some of the issues seen in this age group in the earlier phase 3 studies; in particular the European Medicines Agency (EMEA) agreed to the use of large particle size non-respirable mannitol as the placebo in this study rather than a smaller dose of the active drug as used in the phase 3 trials. As a result the placebo effect seen in this study is minimal and it has therefore not only provided important and reassuring additional evidence on the benefit of BRONCHITOL in the paediatric and adolescent population but also highlighted that the results of the earlier phase 3 studies where a control effect was seen in younger patients may have been understated.”
The 92 subjects randomised and treated had a mean age of 12 years. The mean lung function on entry to the trial was 72.2 per cent of the predicted normal FEV, and 60 per cent of the population were female.
“The young patients entered into this study were already receiving high levels of concomitant medication and had moderately impaired lung function so the improvements shown with BRONCHITOL on top of this standard of care are very welcome. Cross over studies of this type are challenging and I would like to thank everyone involved in the study for their valuable contribution,” added Mr Phillips.