Colistimethate sodium (Promixin®) via I-neb®
Important progress was made in the international program dedicated to the potential treatment of pulmonary infections caused by gram-negative Pseudomonas aeruginosa bacteria in patients suffering from Non-cystic fibrosis bronchiectasis (NCFB) using colistimethate sodium administered by inhalation through the use of the I-neb® nebuliser.
A recalculation of the number of patients needed for the PROMIS 1 trial to have the statistical validity allowed to achieve its recruitment goals without any impact on the quality of the study. The report on this trial is due in 2021.
The impact of the pandemic on the PROMIS 2 trial was mitigated by actions aimed to ensure the recruitment that was completed in 2021.
A liposomal formulation of Cyclosporine-A for inhalation (L-CsA-i) via eFlow®
Bronchiolitis Obliterans Syndrome (BOS) is a progressive inflammatory and fibrotic disease of the respiratory system that commonly develops in patients who have undergone a lung transplant. L-CsA-i is an innovative liposomal formulation of the immunosuppressant drug Cyclosporine-A and created for use via inhalation utilizing a specially designed version of the eFlow® Technology nebulizer system (PARI Pharma GmbH).
Two Phase III trials are currently ongoing (BOSTON-1 and BOSTON-2), involving patients suffering from BOS following lung transplantation. Patients who complete the treatment period in the BOSTON-1 or BOSTON-2 studies will, if eligible, be recruited for the BOSTON 3trial, an observational study to gather long-term efficacy and safety data for the drug. A Phase II clinical trial (BOSTON-4) to evaluate the safety of L-CsA-i for the treatment of adult patients suffering from BOS following allogeneic haematopoietic stem cell transplantation is also underway.
Additional projects in Clinical Phase
In 2020 a Phase I three part, single ascending dose (SAD), multiple ascending dose (MAD) & Cross-Over Study in healthy and asthmatic subjects has been carried out to test the safety and pharmacokinetics of a new dry powder inhaled formulation of the fungicide Voriconazole produced using proprietary E-dry® technology .
The project’s goal is to obtain a new inhalable formulation of Voriconazole to use as a new treatment for Allergic Bronchopulmonary Aspergillosis (ABPA).
Projects in the Preclinical Phase
E-dry® technology is at the basis of two other projects coming down the pipeline in preclinical phase . The first envisions the development of an inhalable formulation of a drug to treat pulmonary infections caused by atypical mycobacteria. . In 2020 the necessary experiments were planned to advance the process of developing the candidate for clinical development. The second project involves a new inhalable formulation of an antioxidant recommended for prophylactic treatment for exposure to particles and chemical substances that are toxic to the organism. In 2020, we concentrated on the preliminary activities necessary for subsequent planning of formulative research.
The Central Nervous System (CNS)
In 2020, Zambon continued to present data about Safinamide (Xadago®) with a symposium at the Movement Disorders Society (MDS) Virtual Congress and a poster at the European Academy of Neurology Virtual Congress. Furthermore, two new articles on the effectiveness of Xadago® for treating pain and cognitive impairment in patients with Parkinson’s Disease were published in the Journal of Neural Transmission.
In 2020 the approval from EMA (European Agency for Medicines) of the clinical study report for the Phase IV observational study “Synapses" was obtained; meanwhile, the Phase IV observational study “Synapses”; meanwhile, the Phase IV European observational study “Success” and the Phase III study “Xindi” for the registration of the drug in China are currently ongoing. Finally, we have 11 investigator-initiated trials (IITs) assessing the effectiveness of safinamide to treat non-motor symptoms, cognitive impairment, freezing of gait, apathy and chronic pain in Parkinson’s Disease. And finally, we received fast-track authorisation for the registration of safinamide in Turkey.
Once again in 2020, Fluimucil® (N-acetylcysteine, NAC), one of the company's historic drugs, was the focus of a series of scientific dissemination activities. The results of the International Expert Panel Meeting held in 2019 were published in the Current Neuropharmacology journal. The purpose of the meeting and, consequently, of the article was to clarify the benefits of using Fluimucil® in different clinical settings. A study was also published in Drug Safety which confirms the tolerability of Fluimucil® when administered off-label at high doses.
In September, at the ERS (European Respiratory Society) International Congress, Zambon sponsored a virtual symposium on the role of Fluimucil® in the treatment of chronic respiratory diseases.
In China, Phase I and III pivotal trials involving approximately 350 patients were completed for the use of intravenous N-acetylcysteine in patients with mucus hypersecretion. The results of a Phase I trial conducted on healthy ethnic Chinese and Caucasian volunteers were also significant. This study showed the same safety and pharmacokinetics results for both groups. The study was published in Advances in Therapy.
An extension phase study on the use of Fluimucil® in patients with retinitis pigmentosa — a rare and serious orphan disease, genetic in nature, which affects the retinal pigment epithelium and the retina, leading to gradual and progressive vision loss — is currently ongoing in the United States.
Urinary tract infections
Monuril® (fosfomycin trometamol) has also been the focus of numerous scientific activities. We are awaiting the publication of data from the international SURF study ,aimed at assessing the rate of antibiotic resistance to fosfomycin trometamol and other antibiotics commonly used in urinary tract infections. Zambon is working with the EMA to conduct a Phase I pharmacokinetic/pharmacodynamic study , which will conclude at the end of 2021. Finally, 2020 saw the organisation of two virtual due Advisory Board on the role of fosfomycin trometamol in different clinical contexts.
Spidifen® (ibuprofen and arginine salt) was also the focus of important activities, such as the publication of the scientific monograph entitled “Nonsteroidal anti-inflammatory drugs, ibuprofen and ibuprofen-arginate”, by Professor Patrono, which aims to highlight the distinct mechanisms of action of different NSAIDs. A scientific Advisory Board was held on the interaction between ibuprofen and Covid-19, with the objective to clear that no connection has been demonstrated between ibuprofen use and a higher risk of being infected by Covid-19 infection.