Utilizing a Novel Modality to Treat Pulmonary Fungal Infections in Lung Transplant Patients

Two patients at a hospital in Australia were administered Thin Film Freezing Voriconazole Inhalation Powder (TFF VORI), which showed treatment efficacy for both patients.

Transplant patients with pulmonary fungal infections can be especially challenging to treat for a whole host of reasons.

“Treatment options for many transplant patients who experience aspergillus fungal infections are often limited due to multiple pre-existing conditions, including skin cancers and intolerance to prior oral voriconazole therapy,” Gregory Snell, MBBS, MD, medical head of Lung Transplant Service at the Alfred Hospital in Melbourne, Australia, said.

With these underlying treatment challenges, clinicians may have limitations for administering oral voriconazole.

Back in early November, TFF Pharmaceuticals, a clinical-stage biopharmaceutical company that develops and commercializes therapies utilizing its patented TFF technology platform, announced that a second patient has been successfully treated with the company’s TFF VORI, a powder that can be delivered to the lungs, which was done through a compassionate use program.

These patients were treated at the Alfred Hospital. Infectious diseases physician Bradley Gardiner, MBBS, was part of the treatment team and presented data from the first patient successfully treated with the inhaled powder formulation at the Annual International Congress on Lung Transplantation in September.

Gardiner explains this modality helps deliver a greater concentration of therapy and avoids the systemic side effects.

The company’s TFF technology platform allows for the transformation of both existing compounds and new chemical entities into dry powder formulations. This is a particle engineering process designed to generate dry powder particles with advantageous properties for inhalation, as well as parenteral, nasal, oral, topical, and ocular routes of administration. The process can be used to engineer powders for direct delivery to the site of need, circumventing challenges of systemic administration and leading to improved bioavailability, faster onset of action, and improved safety and efficacy.

The second lung transplant patient was successfully treated with TFF VORI. The patient had a history of skin cancers and multiple fungal infections. During the prior treatment for the fungal infections with oral voriconazole and posaconazole, the patient experienced hair loss, fatigue, and an increased QTc interval that required discontinuation of two cardiovascular medications. These are well known side effects associated with the use of oral azole antifungals. After discontinuing a recent course of posaconazole, the patient then experienced progressively increased coughing, shortness of breath, and did not respond to oral antibiotics. The patient was subsequently diagnosed with a pulmonary aspergillus infection and experienced declining lung function. Given the toxicities from prior oral azole antifungal therapy and the preexisting skin cancers, the patient was no longer able to tolerate oral voriconazole or other azole antifungals.

Following initiation of TFF VORI therapy, the patient’s lung function stabilized without additional decreases in Forced Expiratory Volume in one second (FEV1) or FEV1/Forced Vital Capacity (FVC) ratios. Consistent with the first patient who received TFF VORI, no dose modification of tacrolimus was required, which is notable due to the well-known severe drug-drug interactions between tacrolimus and oral voriconazole. The patient was on TFF VORI therapy for six weeks and has returned negative cultures for aspergillus in recent specimens obtained from bronchoscopic evaluation. These results support the potential safety and efficacy advantages of TFF VORI, which the company expects to further demonstrate in its phase 2 study.

“This is now the second case that we’ve successfully administered this novel inhaled formulation of voriconazole to a lung transplant patient who could no longer tolerate oral voriconazole therapy,” Snell said. “I am encouraged by the clinical response in this second patient, and we will conduct additional testing in cases where alternative treatment options may be necessary.”

Gardiner spoke with Contagion who provided insights on TFF VORI, and discussed the treatment of one of the aforementioned patients, as well as the potential benefits of having an alternative to oral voriconazole.

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