Bronchitol (mannitol dry powder for inhalation) / Syntara, Arna Pharma - LARVOL DELTA

The Processing Space of the Spray-Dried Mannitol-Leucine System for Pulmonary Drug Delivery. (PubMed, Pharmaceutics) - "The resulting particles were studied initially and at a two-month timepoint via solid state characterization, visual analysis, and particle size analysis in order to detect changes in bulk powder properties. It was determined that, similar to systems where only leucine can crystallize, initial leucine saturation in the formulation dictates powder characteristics."

Journal

Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis (clinicaltrials.gov) - P4 | N=25 | Recruiting | Sponsor: University of North Carolina, Chapel Hill | Not yet recruiting ➔ Recruiting

Enrollment open • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023) (PubMed, Zhonghua Jie He He Hu Xi Za Zhi) - "And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C).Question 12: Does CF require pathological examination as a diagnostic basis?Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D).Question 13: Do CF patients need long-term macrolides?At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A).Question 14: Do CF patients need long-term inhalation of hypertonic saline?Long term treatment with hypertonic saline is recommended for patients with CF(1A).Question 15: Do CF patients need long-term inhalation of Dornase alfa(DNase)?Long term use of DNase is recommended in patients with CF aged 6 years and older(1A).Question 16: Do CF patients need inhalation of mannitol?Inhaled mannitol..."

Journal • Allergic Bronchopulmonary Aspergillosis • Anorexia • Asthma • Bronchiectasis • Cardiovascular • Cough • Cystic Fibrosis • Diabetes • Fatigue • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Hepatology • Hypertension • Immunology • Infectious Disease • Influenza • Metabolic Disorders • Nasal Polyps • Nephrology • Otorhinolaryngology • Pain • Pancreatitis • Pediatrics • Portal Hypertension • Primary Biliary Cholangitis • Pulmonary Disease • Pulmonary Embolism • Rare Diseases • Respiratory Diseases • Respiratory Syncytial Virus Infections • Sinusitis • Transplantation • CFTR

Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis (clinicaltrials.gov) - P4 | N=25 | Not yet recruiting | Sponsor: University of North Carolina, Chapel Hill

New P4 trial • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Dextran Mass Ratio Controls Particle Drying Dynamics in a Thermally Stable Dry Powder Vaccine for Pulmonary Delivery. (PubMed, Pharm Res) - "Overall, dextran-rich formulations increased viscosity during drying which slowed self-diffusion and favorably hindered viral partitioning at the particle surface. Reducing mannitol content also minimized AdHu5 exclusion from crystalline regions that can force the vector to air-solid interfaces where deactivation occurs. Although increased dextran molecular weight improved activity retention at the 1:3 ratio, it was less influential than the ratio parameter. Improving encapsulation ultimately allows inhalable vaccines to be prepared at higher potency, requiring less powder mass per inhaled dose and higher delivery efficiency."

Journal • Respiratory Diseases

Evaluation of the inhaled mannitol tolerance test in children with cystic fibrosis (ECFS 2022) - "Because of the risk of bronchospasm, prior to prescribing mannitol, it is necessary to perform the tolerance test of drag.Objectives: Tо evaluate the inhaled mannitol tolerance test in children with cystic fibrosis.Materials and The mannitol tolerance test (according to the instructions for the Bronchitol (inhaled mannitol), «Pharmaxis Ltd.», Australia) was assessed in 81 children aged 6 to 18 years (11.6±3.2 years)... 90.1% of patients passed the mannitol tolerance test when receiving the initial dose of the drug, 9.9% of patients did not pass the test. During this test, patients are taught the correct inhalation technique. To conduct the test, you must have everything you need and be able to treat severe bronchospasm."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Particle engineering of carriers for improved inhalation formulations (ACS-Sp 2022) - "It was determined that the efficacy, via Fine Particle Fraction (FPF}, of the engineered spray driedlactose-leucine DPI formulation was improved from 25.51 + 1.23% to 47.11 + 9.94%, The performance of the engineered spray dried mannitol-leucine DPI formulation was also improved to 52.96 + 5.21%...Lastly, all of the engineered carriers showedsome degree of agglomeration, which made coarse particles suitable for DP! formulations."

Pharmaxis stocks rising with new drugs coming online in 2022, says broker (Proactiveinvestors) - "Taylor Collison reports that the company’s two FDA-approved respiratory products, Bronchitol for cystic fibrosis (CF) and the Aridol asthma diagnostic, are expected to be profitable on an ongoing basis and to contribute in the vicinity of A$10 million of EBITDA by the 2026 financial year."

Commercial • Asthma • Cystic Fibrosis • Genetic Disorders

EffRx Obtains Swiss Marketing Authorization for Bronchitol in Cystic Fibrosis (Businesswire) - "EffRx Pharmaceuticals...today announced that Swissmedic has approved Bronchitol® (inhaled mannitol) for the treatment of cystic fibrosis (CF) in adults and in children aged 6 years and above as add-on to other medicines....The clinical program supporting the registration of Bronchitol® consisted of three large-scale global clinical trials and enrolled a total of 1,065 subjects....EffRx expects the availability of Bronchitol® in Switzerland in the second half of 2022."

European regulatory • Launch Europe • Cystic Fibrosis

Pharmaxis sells Australian distribution rights for Bronchitol and Aridol for A$2 million (Proactiveinvestors) - "Pharmaxis Ltd (ASX:PXS) (FRA:UUD) will boost its financial position after selling distribution rights in Australia, New Zealand and several Asian territories for its cystic fibrosis product Bronchitol® and asthma diagnostic Aridol® to Bioimpact Pty Ltd, a subsidiary BTC Health Ltd...A distributor appointment fee of A$2 million will be received within 10 business days and Pharmaxis will manufacture and supply the products to BTC Health from its factory in Sydney...Under the terms of the agreement, BTC Health will acquire the marketing authorisations for both products in Australia and New Zealand, Singapore, Malaysia and Hong Kong and in South Korea for Bronchitol only. Pharmaxis will supply both products as finished packs to BTC Health, which has purchased the distribution rights with immediate effect from July 1, 2021..."

Licensing / partnership • Asthma • Cystic Fibrosis • Respiratory Diseases

Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance. (PubMed, Pharm Res) - "The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose."

Journal • Preclinical

Pharmaxis secures $4.4 million in placement to support ongoing myelofibrosis and skin scarring clinical studies (Proactiveinvestors) - "...Pharmaxis also announced today the sale of the distribution rights in Russia for its cystic fibrosis product Bronchitol....Regional pharma specialty company GEN İlaç ve Sağlık Ürünleri San. ve Tic. A.Ş. (GEN) has purchased the rights for A$2 million - effective May 1, 2021....'Pharmaxis steered Bronchitol to approval as the first orphan drug approved in Russia following a change in legislation, listing on the Essential Drugs List and subsequently established a fast-growing business that brought a new drug to cystic fibrosis patients in Russia'....In addition to the sale price, the company has secured ongoing annual savings of A$1 million in marketing and regulatory expenses....Pharmaxis will continue to manufacture and export Bronchitol to Russia from its factory in Sydney that also supplies the US, European and Australian markets."

Commercial • Licensing / partnership • Orphan drug • Cystic Fibrosis

Chiesi USA, Inc. announces Commercial Availability of Bronchitol (mannitol) inhalation powder for improvement in pulmonary function in adult patients with cystic fibrosis (GlobeNewswire) - P3, N=423; NCT02134353; Sponsor: Pharmaxis; "Chiesi USA, Inc…today announced the launch of FDA-approved Bronchitol® (mannitol) inhalation powder, an add-on maintenance therapy to improve pulmonary function in cystic fibrosis (CF) patients 18 years of age and older. Bronchitol is the first and only dry powder inhaled mucoactive agent providing a compact, portable option for patients....Additionally, data from the global Phase 3 study evaluating the efficacy and safety of inhaled dry powder mannitol in adults with CF has been published online in the Journal of Cystic Fibrosis. In the multicenter, double-blind, randomized, parallel-group, controlled study of 423 adults with CF, subjects received either mannitol 400mg or mannitol 50mg (control), twice-daily via dry powder inhaler for 26 weeks....Mannitol 400mg inhaled twice-daily via a dry powder inhaler statistically significantly improved lung function...”

Launch US • P3 data • Cystic Fibrosis • Genetic Disorders

Pharmaxis begins exporting its cystic fibrosis drug Bronchitol to the USA (Pharmaxis Press Release) - “Pharmaceutical research company Pharmaxis Ltd...has announced it has exported the first shipment of its locally developed and manufactured drug Bronchitol (mannitol) to the USA...approved by the US Food and Drug Administration (FDA) on 30 October 2020. Following receipt of an initial payment of US$7 million (~A$10 million) from its exclusive US distributor Chiesi, Pharmaxis will now receive a further US$3 million (~A$4 million) milestone payment....’Bronchitol is approved and PBS listed for the treatment of adults and children in Australia with CF and is also marketed in Europe, Russia and several other countries’."

Commercial • Reimbursement • Cystic Fibrosis • Genetic Disorders

Pharmaxis boosts cash balance with US$7 million milestone payment from US licensee Chiesi following FDA approval of Bronchitol (Proactiveinvestors) - "Pharmaxis...has boosted its cash balance after receiving a US$7 million (~A$9.2 million) milestone payment from US licensee Chiesi Farmaceutici S.p.A. and is well-funded to progress the development of innovative medicines with high patient need...A further US$3 million is payable by Chiesi on shipment by Pharmaxis of commercial launch stock, and this is scheduled for the first quarter of 2021."

Financing • Cystic Fibrosis

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma. (PubMed, Int J Occup Med Environ Health) - "The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9."

Journal • Asthma • Respiratory Diseases

Bronchitol Approved As Add On Therapy For Cystic Fibrosis Patients (Medical Dialogues) - "Bronchitol was developed by Pharmaxis Ltd., and Chiesi is now its exclusive distributor in the United States and 11 other countries. It is mostly found to be indicated in cystic fibrosis (CF) patients 18 years of age and older.'We are excited to achieve its approval in the U.S. for adults living with cystic fibrosis,'...As a result, Chiesi now says it expects the US launch of Bronchitol to take place in March 2021."

Launch US • Cystic Fibrosis

Pharmaxis to get $14m payday after its cystic fibrosis treatment Bronchitol approved by FDA (Stockhead) - "Pharmaxis...the United States Food and Drug Administration approved its inhaled dry powder formulation to treat cystic fibrosis, meaning the Sydney biotech company will be owed $US10 million ($14.3 million) from its launch partner...'We are very pleased that Bronchitol, an Australian drug discovery, will now be available for cystic fibrosis patients in the USA,"..."

Commercial • NDA • Cystic Fibrosis

"FDA Bronchitol Approval to Generate Cash Flows for Pharmaxis https://t.co/5Wtu4aMDHV" (@NewsFromBW)

FDA event

[VIRTUAL] Inhaled mannitol in cystic fibrosis: clinical experience in Verona CF centre (ERS 2020) - "Inhaled mannitol dry powder (Bronchitol®) is a hyperosmotic agent (administred through a handheld inhaler) that hydrates mucus by the same mechanism as hypertonic saline (HS)...Furthermore the easiness of use and duration of inhalation make mannitol a valid option for patients who already have a high treatment burden. The study is still ongoing to assess the long term clinical efficacy of mannitol and establish who can benefit most."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

[VIRTUAL] Investigating the Repeatability of Cough Endpoints from the Mannitol Inhalation Cough Challenge (MICC) (ATS-I 2020) - "There are considerable differences in the repeatability of cough endpoints in a mannitol inhalational cough challenge and some subjects may not achieve C2 or C5. Emax was the only endpoint quantifiable in all subjects."

Asthma • Respiratory Diseases • JAK3

[VIRTUAL] The Effect of Nebulized Salbutamol on Mannitol Evoked Cough Responses in Mild Allergic Asthmatics: A Double-Blind Randomized Placebo Controlled 2-Way Cross-Over Study (ATS-I 2020) - "At visit 2, a mannitol inhalational cough challenge (MICC) was performed... Cough responses to inhaled mannitol can be attributed to a combination of bronchoconstriction and activation of airway nerves, which was reduced by salbutamol. The receptors and nerves involved require further investigation."

Clinical • Asthma • Respiratory Diseases

[VIRTUAL] Mannitol Evoked Cough Responses; Evidence of Neuronal Dysfunction in Allergic Asthmatics and Females (ATS-I 2020) - "At visit 2, a mannitol inhalational cough challenge (MICC) was performed... Allergic asthma and sex, independent of % fall in FEV1, influence cough responses to a hyper-osmolar mannitol cough challenge. The nerves and receptors involved in coughing due to hyper-osmolarity require further attention with the hope of developing novel anti-tussives targeting airway nerves."

Asthma • Immunology • Respiratory Diseases

Long-term tolerability of inhaledmannitol in adultswith cystic fibrosis (ECFS 2020) - "94% (n = 32) passed the Bronchitol Initiation Dose Assessment (BIDA) with 73% continuing as part of maintenance treatment following review at 6 weeks... Whilst IM is shown to be well tolerated in the short term discontinuation rates are higher with use beyond 1 year. There is a trend for higher rates of intolerance in patients with more severe disease, particularly where lung function is outside licence parameters."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases • Transplantation

The use of Dry Powder Mannitol (DPM) – experience at a large adult cystic fibrosis centre (ECFS 2020) - "Objectives: Although DPM for inhalation (Bronchitol®) has been licensed in the UK since 2012 for use in pwCF as a mucolytic agent, uptake has been limited... We have found DPM to be a safe and effective mucolytic therapy. Importantly, we have found benefits when using this drug in acute exacerbations and continue to explore this option."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases