TFF Pharmaceuticals Announces Final Data From Phase 1b Study of Inhaled Voriconazole Powder in Asthma Patients

TFF Pharmaceuticals, Inc. recently announced the full readout of safety and pharmacokinetic (PK) data from its Phase 1b study (NCT #04576325) of Inhaled Voriconazole Powder (TFF VORI) in asthma patients.

TFF VORI is a next-generation, direct-to-lung, inhaled dry powder formulation of voriconazole for the treatment and prevention of Invasive Pulmonary Aspergillosis (IPA). TFF Pharmaceuticals’ proprietary Thin Film Freezing technology platform allows the reformulation of voriconazole into a dry powder with properties ideally suited for inhalation. The data reported from the Phase 1b study are consistent with the initial data reported in November suggesting that TFF VORI is well tolerated in asthma patients and could therefore provide a differentiating benefit to a broad population of patients with IPA.

“The final data from our Phase 1b reactive airway study in patients with asthma confirm earlier readouts that TFF VORI appears to be well tolerated in a patient population that is vulnerable to IPA infections, but can be challenging to treat because inhaled anti-infective therapies can trigger bronchospasm,” said Glenn Mattes, President and CEO of TFF Pharmaceuticals. “The broad therapeutic applications of our Thin Film Freezing technology continue to grow, and with this latest data readout we are now poised to advance one of our key internal product candidates into late-stage clinical testing in 2022.”

Voriconazole is recommended as the first line treatment for IPA according to the Infectious Disease Society Practice Guidelines for the Diagnosis and Management of Aspergillosis (2016) but is associated with significant drug-drug interactions and toxicities. Delivery of voriconazole directly to the lung via TFF’s inhaled formulation may allow for greater efficacy than orally administered voriconazole and improved safety through reduced systemic toxicities and reduced drug-drug interactions.

Patients with asthma and a portion of patients with cystic fibrosis and chronic obstructive pulmonary disease (COPD) 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. Many of these patients are taking other inhaled antibiotics that require treatment with a short acting bronchodilator prior to administration.

TFF Pharma’s Phase 1b study was a randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, pharmacokinetics, and induction of bronchospasm of TFF VORI in 16 patients with mild to moderate asthma who were also using bronchodilators daily for asthma treatments. All of the patients’ airways in this study were considered reactive and could be triggered to bronchospasm.

The data show that TFF VORI was well tolerated in asthma patients and indicate that no drug-drug interactions with bronchodilators will limit the use of these common asthma medications in patients with reactive airway disease. The Company anticipates enrolling patients who are prescribed a bronchodilator for its planned Phase 2 trial in IPA patients in 2022.

Additional details from the study are below:

• The study was comprised of two cohorts. In cohort 1, 8 eligible subjects were randomized in a 3:1 ratio (6 on active and 2 on placebo) to receive 7 doses over 3.5 days of 40-mg TFF VORI or inhaled placebo. In cohort 2, 8 eligible subjects were also randomized in a 3:1 ratio to receive 7 doses over 3.5 days of 80 mg TFF VORI or placebo. In both cohorts, doses were administered twice daily every 12 (± 1) hours.
• Systemic PK data following repeated dosing with an 80-mg twice daily dose showed no statistical differences between absorption and clearance between subjects with healthy lungs from the Phase 1 trial and asthma patients with diseased lungs in this Phase 1b study, supporting selection of an 80-mg dose for future clinical studies in IPA patients.
• Observational data from the Phase 1b trial support the inclusion of patients that have hyperreactive airway disease comorbidities in the Phase 2 trial and suggest that TFF VORI also may have the potential to treat Allergic Bronchopulmonary Aspergillosis (ABPA), which impacts up to 2.5% of asthma patients (an estimated 600,000 patients in the US).

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%.

TFF Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative drug products based on its patented Thin Film Freezing, or TFF, technology platform. Early testing confirms that the TFF platform can significantly improve the solubility and absorption of poorly water-soluble drugs, a class of drugs that comprises approximately one-third of the major pharmaceuticals worldwide, thereby improving their pharmacokinetics. TFF Pharmaceuticals has two lead drug candidates: Inhaled Voriconazole Powder and Inhaled Tacrolimus Powder. The company plans to add to this pipeline by collaborating with large pharmaceutical partners. The TFF Platform is protected by 42 patents issued or pending in the US and internationally. For more information, visit https://tffpharma.com.