TFF Pharmaceuticals said that a Phase 1 SAD/MAD study of its tacrolimus inhalation powder, which the company is developing for the prevention of lung transplant rejection, demonstrated that the dry powder formulation can be dosed to achieve lung and blood concentrations of tacrolimus necessary for efficacy without causing kidney toxicity. Based on the Phase 1 results, TFF said that it “expects to take critical steps toward beginning its Phase 2 clinical study” of the inhaled tacrolimus by the end of the year.
The company announced initiation of the Phase 1 trial in June 2020, the same month that the tacrolimus inhalation powder received orphan drug designation from the FDA for prevention of lung transplant rejection. The single ascending dose portion of the trial evaluated 0.5 mg, 1 mg, 2.5 mg, and 5 mg doses in healthy volunteers. The multiple ascending dose portion evaluated twice daily dosing of 0.5 mg and 1.0 mg doses for 7 days and once daily dosing of 1.5 mg for 7 days.
The proposed Phase 2 trial is expected to enroll lung transplant patients who are taking oral tacrolimus and experiencing kidney toxicity. Those patients will get doses of inhaled tacrolimus tailored to achieve a blood level deemed appropriate for the specific patient, and dosing will be adjusted weekly as necessary.
TFF CEO Glenn Mattes said, “The data from this Phase 1 study suggests that tacrolimus inhalation powder can be administered with an acceptable safety profile to achieve the appropriate balance of local and systemic concentrations for immunosuppression at the site of the lung transplant while minimizing the risk of supra-therapeutic systemic exposure well known to cause substantial renal toxicity in these patients. We believe the strong dose-dependent PK data with pulmonary administration will allow a flexible dosing regimen that can be tailored to each patient, consistent with the manner in which these patients are managed in the real-world setting. This flexible dosing approach will also be reflected in the design for our upcoming Phase 2 study in lung transplant recipients.”
Read the TFF Pharmaceuticals press release.
