TFF Pharmaceuticals, a pharmaceutical firm that uses its proprietary thin-film freezing technology on drug products, has completed dosing in the Phase Ib trial of voriconazole inhalation powder (TFF VORI), a direct-to-lung inhaled powder version of the drug. The therapy is intended to treat and prevent invasive pulmonary aspergillosis (IPA), a condition that patients with mild to moderate asthma are at risk of developing.
According to the company, the study impacted two cohorts of eight patients. Initial data from the study reportedly indicates the treatment is well tolerated in asthma patients, leading the way to a Phase II study involving IPA patients.
“We are pleased to have reached another important clinical milestone in our Inhaled Voriconazole program,” said Glenn Mattes, TFF Pharmaceuticals president and CEO. “By assessing asthma patients in this Phase 1b reactive airway, we hope to demonstrate that our voriconazole inhalation powder would allow for treatment of patients with IPA that have hyperreactive airway disease comorbidities. We look forward to providing specific data from this trial later in the year.”
The company added that observational data from the Ib trial would support the inclusion of patients dealing with hyperreactive airway disease comorbidities in the Phase II trial. What’s more, TFF suggests, this indicates TFF VORI also may have the potential to treat allergic bronchopulmonary aspergillosis (ABPA) which impacts up to 2.5% of asthma patients.
Patients with asthma and a portion of patients with cystic fibrosis and chronic obstructive pulmonary disease (COPD) reportedly are susceptible to IPA infections due to impaired mucociliary clearance but have hyperreactive airways where bronchoconstriction can be triggered following administration of drugs by inhalation.
Carsten Schwarz, director of the Cystic Fibrosis Center, said the results of the study are encouraging for patients with hyperreactive airways.
“By delivering voriconazole directly to the site of infection, TFF VORI offers the potential for treatment of IPA patients that could be both safer and more effective than the current formulation,” Schwarz said. “It could also be used as a prophylactic to prevent IPA in at-risk populations.”
Data suggests drugs intended to treat pulmonary infections can be associated with induction of bronchospasm and require bronchodilator pretreatment for safe administration. Previous studies of approved inhaled antibacterial drugs reportedly have shown that up to 3% of patients (asthma and non-asthma) experience bronchospasm, necessitating a label requirement that patients first receive pretreatment with a short-acting bronchodilator prior to administration of the antibiotic.
According to TFF, the observational data from the Phase Ib trial indicates that TFF VORI is well tolerated in asthma patients. Currently, voriconazole is recommended as the first-line treatment for IPA according to Infectious Disease Society (IDSA) aspergillosis guidelines; however, voriconazole is associated with significant drug-drug interactions and toxicities. Delivery of voriconazole directly to the lung may allow for a product with greater efficacy than orally administered voriconazole, and with improved safety through reduced systemic toxicities and reduced drug-drug interactions.
TFF Pharmaceuticals’ proprietary thin-film freezing technology, designed to improve solubility and absorption of drugs, reportedly enables reformulation of voriconazole into dry powder particles with properties believed to be suited for inhalation delivery.