MC has said Mnkd excluded 2 compounds from UTHR Deal. They are likely Tobra-T, DNase, both for CF. Mnkd is looking to partner for these Bucket-1.
Protalix BioTherapeutics Announces Positive Results from Phase II Clinical Trial of alidornase alfa (AIR DNase™) for the Treatment of Cystic Fibrosis
Positive Results in a Number of Clinically Relevant Parameters Suggest Improved Lung Function with alidornase alfa
CARMIEL, Israel, April 12, 2017 (GLOBE NEWSWIRE) -- Protalix BioTherapeutics, Inc. (NYSE MKT:PLX) (TASE:PLX), announced today positive results from the Company’s phase II clinical trial of alidornase alfa for the treatment of Cystic Fibrosis (CF). Sixteen patients were enrolled in the study, all of whom completed the study. alidornase alfa is a plant cell-expressed, chemically-modified recombinant DNase enzyme resistant to inhibition by actin, which the Company has specifically designed to enhance the enzyme’s efficacy in CF patients.
The phase II trial is a 28-day switchover study to evaluate the safety and efficacy of alidornase alfa in CF patients previously treated with Pulmozyme® (currently the only commercially available DNase therapy). Participation in the trial was preceded by a two-week washout period from Pulmozyme® before treatment with alidornase alfa via inhalation.
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.
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 the modulator on top of Pulmozyme®. 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 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 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.
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 CF patients.
The above-mentioned material decrease in visco-elasticity and DNA presence in CF 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.
“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,” said Professor Eitan Kerem, Chairman of Pediatrics, Head of The Cystic Fibrosis Center, Hadassah University Hospital, and a Principal Investigator in the clinical trial. “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.”
“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,” commented Moshe Manor, Protalix’s President and Chief Executive Officer. “We look forward to exploring different paths for advancing the clinical development of alidornase alfa.”
Data from the study was accepted as an oral presentation at the 40th European Cystic Fibrosis Conference to be held in June 2017.
phx.corporate-ir.net/phoenix.zhtml?c=101161&p=irol-newsArticle&ID=2261531www.pulmozyme.com/hcp/cf-treatment/pulmozyme-moa.htmlBy Genentech of the Roche Group.
Pulmozyme (dornase alfa) is indicated for daily administration in conjunction with standard therapies for the management of cystic fibrosis (CF) patients to improve pulmonary function.
In CF patients with an FVC ≥ 40% of predicted, daily administration of Pulmozyme has also been shown to reduce the risk of respiratory tract infections requiring parenteral antibiotics.
PEDIATRIC USE
The safety and effectiveness of Pulmozyme have been established in pediatric patients 5 years of age and older. The safety of Pulmozyme, 2.5 mg by inhalation, was studied with 2 weeks of daily administration in 65 patients with cystic fibrosis aged 3 months to < 5 years. While clinical trial data are limited in pediatric patients younger than 5 years of age, the use of Pulmozyme should be considered for pediatric CF patients who may experience potential benefit in pulmonary function or who may be at risk of respiratory tract infection.
The safety of Pulmozyme, 2.5 mg by inhalation, was studied with 2 weeks of daily administration in 98 pediatric patients with cystic fibrosis 3 months to 10 years of age (65 aged 3 months to < 5 years, 33 aged 5 to ≤ 10 years). The PARI BABY™ reusable nebulizer (which uses a facemask instead of a mouthpiece) was utilized in patients unable to demonstrate the ability to inhale or exhale orally throughout the entire treatment period (54/65, 83% of the younger; and 2/33, 6% of the older patients).