Pharmaxis's Bronchitol positive in Phase III for cystic fibrosis
This article was originally published in Scrip
Pharmaxis's cystic fibrosis treatment, Bronchitol, has met the primary endpoint of improvement in lung function in its first Phase III study.
"The leading reason for patients to die from cystic fibrosis is a gradual decline of lung function, and patients decline at an average rate of 1% to 2%," said Pharmaxis's chief executive, Dr Alan Robertson. Bronchitol is a proprietary dry-powder mannitol, designed to be delivered through a portable inhaler.
The Sydney, Australia-based company says that the trial was one of the biggest ever conducted in cystic fibrosis patients. Bronchitol is also in an ongoing second Phase III study, which will be used to support the product's US filing.
Pharmaxis plans to file Bronchitol in the EU towards the end of the third quarter. It is still working on a pharmacokinetic study, which it anticipates will be finished by the submission.
"My hope is that we can get Bronchitol onto the market towards the latter part of next year," said Dr Robertson. He added that the company had not yet decided how Bronchitol would be priced.
The trial enrolled 324 subjects, who had an average age of 23 years. A mean lung function of 62% of normal forced expiratory volume in one second (FEV1), and 55% of the population was using the most common medication for cystic fibrosis, Roche's Pulmozyme (dornase alfa). Patients who displayed some bronchial hypersensitivity or lung obstruction issues were excluded from the cohort.
Patients were randomised to receive 400mg of Bronchitol twice a day for six months or placebo, in addition to their normal regimens. The primary endpoint was to assess whether Bronchitol improved lung function as measured by a change in FEV1 after six months of treatment. The secondary endpoint assessed whether Bronchitol further improved lung function in patients already being treated with Pulmozyme.
Patients treated with Bronchitol alone experienced a 6.6% significant improvement in FEV1 versus placebo (p=0.001). According to the company, lung function improved at week six and was sustained through to week 26. When used concurrently with Pulmozyme, patients achieved a 5.2% increase in FEV1 (p=0.002) after 26 weeks. A 6.6% improvement equates to an average gain of 122ml of lung capacity. The trial also saw a lung capacity improvement of 20ml with placebo; the company offered no explanation for this.
The company said that the exacerbation data are consistent with the FEV1 results, and will be presented at an upcoming cystic fibrosis medical meeting. "Clinicians are still in desperate need of new treatments … They are definitely looking for other therapies which can produce additional efficacy on top of what Pulmozyme is already delivering," said Dr Robertson, commenting on Bronchitol's potential place in the market.
"And there is obviously a group who will be doing quite well on Pulmozyme initially, but inevitably, over time these patients will deteriorate and they will be looking for other medications. There is also people who have failed on Pulmozyme, or are intolerant to it, who will be looking for other medications."