Clinical Trials

Date: 2017-06-07

Type of information: Presentation of results at a congress

phase: 2

Announcement: presentation of results at the 40th European Cystic Fibrosis Society Conference

Company: Protalix BioTherapeutics (Israel)

Product: alidornase alfa AIR DNase™ (PRX-110)

Action mechanism:

• enzyme. AIR DNase is a plant cell derived recombinant form of human deoxyribonuclease I (DNase I) that Protalix has designed, through chemical modification, to be resistant to inhibition by actin. Given actin is a potent inhibitor of DNase I activity, AIR DNase has the potential to enhance the enzyme’s efficacy significantly in cystic fibrosis patients when compared to the currently approved DNase treatment (Pulmozyme®).

Disease: cystic fibrosis

Therapeutic area: Rare diseases - Genetic diseases

Country: Israel

Trial details:

• The phase II trial is a 28-day switch-over study to evaluate the safety and efficacy of alidornase alfa in cystic fibrosis patients previously treated with Pulmozyme®. Participation in the trial is preceded by a two-week washout period from Pulmozyme® before treatment with alidornase alfa via inhalation. Sixteen patients were enrolled in the study, all of whom completed the trial.(NCT02722122)

Latest news:

• • On June 7, 2017, Protalix BioTherapeutics announced  that an oral presentation highlighting the results from the phase II clinical trial of alidornase alfa (PRX-110) for the treatment of Cystic Fibrosis (CF) and including new clinical data has been given at the 40th European Cystic Fibrosis Society Conference. The oral presentation, titled “Phase II clinical trial results of alidornase alfa for the treatment of cystic fibrosis,” has been given by Professor Eitan Kerem, Head of the Division of Pediatrics, Children’s Hospital, Hadassah Medical Center, and principal investigator of the clinical trial.
• In accordance with the trial design, each participating patient was tested at three major time-points during the study for percent predicted forced expiratory volume in one second, or ppFEV1, a key efficacy measure. The first ppFEV1 test was performed at screening, when the patient was still being treated with Pulmozyme®. The second ppFEV1 test was performed after the patient underwent a two-week washout period from Pulmozyme® but before first inhalation with alidornase alfa – the baseline – and the third ppFEV1 test was performed at the end of the 28-day study after the patient underwent daily inhalation treatments of alidornase alfa.
• Final analysis of the data demonstrated a mean absolute increase in ppFEV1 of 3.4 points from baseline, and an increase in ppFEV1 of 3.3 points, when compared to measurements taken from patients at enrollment before the switch from Pulmozyme® to alidornase alfa.
• In addition to the ppFEV1 measurements taken during the study, an additional ppFEV1 measurement was taken two weeks after patients stopped treatment with alidornase alfa. For this measurement point, a mean decrease in ppFEV1 of -2.7 points was observed from the last alidornase alfa inhalation, while patients taken off Pulmozyme® at the beginning of the trial for two weeks experienced a mean decrease in ppFEV1 of only 0.06 points for the same off treatment duration. A graph describes the change in ppFEV1 for all four measurement points. The results highlight the quick and sustained effect of alidornase alfa.
• Sputa available samples were analyzed for approximately half of the patients participating in the study. For these samples, a mean reduction from baseline of over 70% in DNA content and over 90% for sputa visco-elasticity was demonstrated. Additionally, a clear correlation between improvement in sputa parameters and pulmonary function was observed. Moreover, a significant increase in DNA content and sputa visco elasticity was observed during the two weeks after stopping treatment with alidornase alfa, with a clear correlation between the decrease in pulmonary function and sputa parameters, as demonstrated in the graph.
• In addition, analysis of the presence of Pseudomonas aeruginosa in patients available sputum samples was evaluated using qPCR. The analysis demonstrated a reduction of over 70%, compared to baseline, in the presence of pseudomonas as a result of alidornase alfa treatment. This is in line and consistent with the previously announced in vitro study of alidornase alfa which demonstrated a significant inhibition of pseudomonas aeruginosa, with colonies reduced by over 50%, compared to baseline. Pseudomonas are a major cause of lung infections in CF patients. Chronic pulmonary infection is a leading cause of morbidity and mortality in CF patients, despite the aggressive use of antibiotics, and pseudomonas is the most prevalent organism in the airway colonization of CF patients. Alidornase alfa was well tolerated with no serious adverse events reported, and all adverse events that occurred during the study were mild and transient in nature.
• • On April 12, 2017, Protalix BioTherapeutics announced positive results from the phase II clinical trial of alidornase alfa for the treatment of cystic fibrosis. Sixteen patients were enrolled in the study, all of whom completed the study. The primary efficacy results show that treatment with alidornase alfa resulted in clinically meaningful lung function improvement, as demonstrated by a mean absolute increase in the percent predicted forced expiratory volume in one second (ppFEV1) of 3.4 points from baseline. Moreover, a mean absolute increase in ppFEV1 of 2.8 points was also observed in patients participating in the trial when compared to measurements taken from patients at initiation before the switch from Pulmozyme® to alidornase alfa.
• Sputa available DNA samples were analyzed for approximately half of the patients. A mean reduction of over 70% in DNA content from baseline was observed, and a mean reduction of over 90% from baseline was observed for sputa visco-elasticity. Correlation between improvement in sputa parameters and pulmonary function was observed.
• In addition, an in vitro study of alidornase alfa demonstrated a significant inhibition of Pseudomonas Aeruginosa, with alidornase alfa treated colonies reduced by over 50%, compared to baseline. Pseudomonas, strains of bacteria that are widely found in the environment, are a major cause of lung infections in cystic fibrosis patients. Chronic pulmonary infection is a leading cause of morbidity and mortality in cystic fibrosis patients, despite the aggressive use of antibiotics, and Pseudomonas is the most prevalent organism in the airway colonization of cystic fibrosis  patients.
• PK analysis performed indicated alidornase alfa is not absorbed into a patient’s circulatory system, suggesting higher levels of alidornase alfa remains available in the patient's lungs. This provides further support for the potential that alidornase alfa may offer additional efficacy to cystic fibrosis  patients.
• The above-mentioned material decrease in visco-elasticity and DNA presence in cystic fibrosis patients’ sputa, coupled with the significant inhibition of Pseudomonas and higher levels of alidornase alfa available in the patients’ lungs, provides further supportive evidence of improved lung function after treatment with alidornase alfa, as demonstrated by the increase in FEV1.
• Alidornase alfa was well tolerated with no serious adverse events reported, and all adverse events that occurred during the study were mild and transient in nature.
• Data from the study was accepted as an oral presentation at the 40th European Cystic Fibrosis Conference to be held in June 2017.
• • On January 3, 2017, Protalix BioTherapeutics announced positive interim results from the phase II clinical trial of alidornase alfa for the treatment of cystic fibrosis for the first 13 patients enrolled in the study. Fifteen patients have been enrolled in, and are expected to complete, the study. The initial primary efficacy result shows that alidornase alfa improves lung function as demonstrated by a mean absolute increase in the percent predicted forced expiratory volume in one second (ppFEV1) of 4.1 points from baseline. A commercially available small molecule CFTR modulator for the treatment of CF has reported a mean absolute increase in ppFEV1 of 2.5 from baseline in its registration clinical study. This score was achieved while 74% of the patients participating in the trial of the CFTR modulator were also treated with Pulmozyme® on top of the modulator. While this marketed CFTR addresses a certain mutation applicable to less than 50% of CF patients, alidornase alfa is being developed to treat all CF patients.
• Sputa available DNA samples were analyzed for approximately half of the patients. A mean reduction of approximately 60% in DNA content from baseline was observed, and a mean reduction of approximately 90% from baseline was observed for sputa visco-elasticity. This data provides further supportive evidence of improved lung function after treatment with alidornase alfa, as demonstrated by the increase in ppFEV1. No serious adverse events were reported, and all adverse events that occurred during the study were mild and transient in nature. Protalix BioTherapeutics is now looking forward to reporting full results from the study before the end of the first quarter of 2017.
• • On December 22, 2016, Protalix BioTherapeutics announced that the last patient has been enrolled in the Company’s phase II clinical trial of AIR DNaseTM (PRX-110) for the treatment of cystic fibrosis. The Company expects to report interim top-line results from this study during the first week of January 2017, and full results before the end of the first quarter of 2017. The phase II trial is a 28-day switch-over study of 15 CF patients previously treated with Pulmozyme® to evaluate the efficacy and safety of AIR DNase in CF patients. Patients that have participated in the trial have undergone a two-week washout period, in which they were not treated with Pulmozyme, before dosing with the Company’s AIR DNase. The main efficacy endpoint is the change of forced expiratory volume (FEV1) and forced vital capacity (FVC). Additional endpoints include safety and tolerability, immunogenicity and pharmacokinetic data. In the trial, AIR DNase is administered through Philips Respironics' I-neb AAD Inhaler System, for which the Company has a supply agreement for the exclusive use of the device for the development of an inhaled product based on dornase alfa for the treatment of CF. The I-neb AAD is a small, lightweight, virtually silent device that is fully portable and has a unique vibrating mesh technology that allows for faster administration than conventional jet or ultrasonic nebulizers.
• • On July 7, 2016, Protalix BioTherapeutics announced  the first patient has been dosed in the phase II clinical trial of AIR DNase™ (PRX-110) for the treatment of cystic fibrosis .  The phase II trial is a 28-day switch-over study of 15 cystic fibrosispatients previously treated with Pulmozyme® to evaluate the efficacy and safety of AIR DNase in cystic fibrosis patients. The patients will undergo a two-week washout period, in which they will not be treated with Pulmozyme, before dosing with the Company’s AIR DNase. The main efficacy endpoint is the change from baseline of forced expiratory volume (FEV1) and forced vital capacity (FVC). Additional endpoints include safety and tolerability, immunogenicity and pharmacokinetic data.
• Protalix has signed a supply agreement with Philips Respironics for its I-neb AAD Inhaler System which gives the Company exclusive use of the device for the development of an inhaled product based on dornase alfa for the treatment of CF, and the Company is using the device to deliver AIR DNase in the clinical trial. The I-neb AAD is a small, lightweight, virtually silent device that is fully portable and has a unique vibrating mesh technology that allows for faster administration than conventional jet or ultrasonic nebulizers.
• The phase II clinical trial is expected to complete enrollment in the second half of 2016. Top-line results are expected to be available around year-end.

Is general: Yes