Small Phase 2 Trial Indicates Protalix’s Therapy Might Improve CF Lung Function

A small proof-of-concept Phase 2 trial (NCT02722122) of alidornase alfa showed that the therapy improved lung function in patients with cystic fibrosis (CF), according to its developer Protalix BioTherapeutics.

In addition to making breathing difficult, the thick mucus in CF patients’ airways makes ideal growth conditions for many bacterial species. Chronic lung infections are the main reason for declining lung function in CF. Alidornase alfa consists of a modified plant-derived enzyme that chops up DNA in the mucus. This thins the mucus, making it easier to cough up.

But as the trial was small and did not directly compare alidornase alfa to the currently only approved drug that uses the same approach to make the mucus in CF patients’ airways less sticky, Pulmozyme (dornase alfa). Therefore, the results of the study need to be viewed as preliminary.

The trial enrolled 16 patients, one more than was stated in the trial protocol. Participants had all been previously treated with Pulmozyme and stopped the treatment two weeks before starting the alidornase alfa therapy.

Patients received inhaled alidornase alfa for 28 days.

The company reported a 3.4 point increase from baseline in the percent predicted forced expiratory volume in one second (ppFEV1) after completion of the treatment (ppFEV1 is a commonly used measure of lung function).

They also added that, compared to the values taken just before patients quit Pulmozyme, the improvement in ppFEV1 was 2.8 points.

Protalix company officials argued that the results were better than those seen with a treatment using a commercially available small molecule CFTR modulator, but did not disclose which drug they were referring to.

CFTR modulators belong to a different type of drug which addresses the underlying cause of cystic fibrosis by correcting the flawed protein made by the CFTR gene. Alidornase alfa is, instead, targeting a symptom of the disease, so a comparison between the two compounds adds little value.

In fact, CFTR modulators and Pulmozyme are often used together. The two drugs were also not directly compared in the trial.

In an interim analysis of the study, data from 13 patients showed an improvement in ppFEV1 of 4.1 points. To validate the effectiveness of its drug candidate, Protalix needs data from larger trials.

Analyses of sputum samples showed that the treatment lowered DNA content in the mucus by 70%, and the viscoelasticity by over 90%. These measures correlated with better lung function.

“The efficacy and safety results of alidornase alfa are very encouraging as they demonstrate data that are clinically relevant, which brings new hope to CF patients living with this devastating disease,” Eitan Kerem, the trial’s principal investigator, said in a press release.

“I look forward to taking part in future clinical studies of alidornase alfa as I believe it has the potential to become a gold standard treatment for all CF patients,” added Kerem, who is a professor, chairman of pediatrics, and head of The Cystic Fibrosis Center at Hadassah University Hospital.

The study’s primary endpoint was the analysis of safety data. The company reported that alidornase alfa was well tolerated by patients. All adverse events during the trial were mild and transient, with no serious adverse events reported.

Analyses also showed the drug did not enter the bloodstream after inhalation. Since the drug is intended to act locally in the airways, this potentially makes it more effective and reduces the risk of side effects.

Protalix also measured the amount of Pseudomonas aeruginosa in the sputum. According to the company, the treatment reduced bacterial colonies by over 50% compared to the start of the study. Pseudomonas aeruginosa is the major bacterial species colonizing CF patients’ airways.

“We are very excited with the clinical data showing a significant, clinically meaningful improvement in efficacy, and potentially offering new alternatives to all CF patients,” said Moshe Manor, Protalix’s president and CEO. “We look forward to exploring different paths for advancing the clinical development of alidornase alfa.”