Phase 1 clinical study report for Voriconazole Inhalation Powder indicated no treatment emergent adverse events at peak plasma levels for Invasive Pulmonary Aspergillosis
Phase 1 Single Ascending Dose study of Tacrolimus Inhalation Powder met and exceeded therapeutic drug levels with a single dose with no significant adverse events reported
Voriconazole Inhalation Powder
The Phase 1 clinical trial of Voriconazole Inhalation Powder for the treatment of invasive pulmonary aspergillosis (IPA), an inhaled dry powder version of voriconazole, has been successfully completed and comprehensive safety and pharmacokinetic data is now available following delivery of the clinical study report. Voriconazole is recommended as the first line treatment for IPA according to the
Through completion of the Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) cohorts, TFF demonstrated that doses of 10, 20, 40, and 80 mg could be delivered twice daily using a dry powder inhaler device with no significant adverse events. There was no evidence of treatment-related or dose-related trends in the reporting of treatment emergent adverse events, throughout the study. No subjects experienced any dose limiting toxicity events during the study.
“This Phase 1 clinical trial safety data has dramatically exceeded our expectations for Voriconazole Inhalation Powder,” stated
Voriconazole Inhalation Powder is being developed by TFF to treat IPA with the goal of enhancing efficacy through more efficient delivery of the drug to the lung relative to the oral or intravenous forms of Vfend®, where blood levels can reach greater than 5,000 ng/mL in order to deliver sufficient voriconazole to the lung. However, drug levels greater than 5,000 ng/mL in the blood are associated with severe adverse events including liver kidney and visual toxicities.
Evaluation of the pharmacokinetic profile of the Voriconazole Inhalation Powder demonstrated that mean peak plasma voriconazole levels reached concentrations of 227 ng/mL following repeated dosing at 80 mg twice daily for 7 days, without any reports of adverse events.
“Now that we have the final data from this Phase I trial, we have confidently selected the 80 mg dose of Voriconazole Inhalation Powder for our upcoming pivotal trial, where we will be comparing it to the oral form of voriconazole,” said Mattes. “We expect to continue to see a more favorable adverse events profile in the inhalable arm, and equal to or greater efficacy when compared to oral voriconazole.”
“We’re excited for the future development of Voriconazole Inhalation Powder because we feel it can achieve our target product profile of having better efficacy than oral voriconazole by delivering a greater amount of drug directly to the site of the infection, and of having fewer adverse effects than voriconazole that is dosed systemically to achieve drug levels able to reach the lung,” said Mattes.
In addition to the release of the final data from the Phase 1 clinical trial, TFF is continuing to enroll asthma patients in a Phase 1b study to understand if the Voriconazole Inhalation Powder is likely to trigger bronchospasm in patients with hyperreactive airway disease. Other inhaled anti-infective drugs have demonstrated this effect and require pretreatment with a bronchodilator prior to dosing. TFF is completing this reactive airway study to guide the clinical practice in patients with hyperreactive airway diseases (Asthma and COPD). The data from this study and from the completed healthy normal Phase 1 study will lead to the initiation of a pivotal study of Voriconazole Inhalation Powder, which will begin enrolling patients later this year.
Tacrolimus Inhalation Powder
“The ability to efficiently reach therapeutic drug levels with our Tacrolimus Inhalation Powder following just a single dose without any significant adverse events is very significant and ahead of our expectations,” said Mattes. “Achieving therapeutic blood levels efficiently, with low doses of the inhaled powder, suggests that our product may have application beyond lung transplant, potentially in heart, kidney and liver transplant patients.”
In clinical practice, tacrolimus blood levels are monitored and controlled to achieve blood levels that are known to be associated with efficacious immunosuppression, while not elevating the blood concentration to levels associated with toxicities. For lung transplant patients, therapeutic drug monitoring (TDM) is used to achieve maintenance tacrolimus levels from 5-15 ng/mL after transplant to prevent acute allograft rejection1. The Phase 1 study of Tacrolimus Inhalation Powder utilized TDM measurements to determine when a sufficient dose level had been reached.
“We look forward to the additional safety and pharmacokinetic data that will be produced during the dosing of the remaining MAD cohorts as we complete this study and prepare for pivotal trials of this promising therapy,” concluded Mattes. “We expect to have final safety data completed by the end of the second quarter of 2021, enabling us to move into the pivotal trial phase in the second half of the year.”
Immunosuppression in lung transplantation
J Thorac Dis. 2014 Aug; 6(8): 1039–1053. doi: 10.3978/j.issn.2072-1439.2014.04.23
About TFF Pharmaceuticals’ Thin Film Freezing technology platform
TFF Pharmaceuticals’ Thin Film Freezing (TFF) platform was designed to improve the solubility and absorption of poorly water-soluble drugs and is particularly suited to generate dry powder particles with properties targeted for inhalation delivery, especially to the deep lung, an area of extreme interest in respiratory medicine. The TFF process results in a “Brittle Matrix Particle,” which possesses low bulk density, high surface area, and typically an amorphous morphology, allowing the particles to supersaturate when contacting the target site, such as lung tissue. Based upon laboratory experiments the aerodynamic properties of the particles are such that the portion of a drug deposited to the deep lung has the potential to reach as high as 75 percent.
This press release contains forward-looking statements regarding
Investor Relations and Media Contact: