TFF Pharmaceuticals Receives Approval from Health Canada to Enter Human Clinical Trials for Inhaled Formulation of Niclosamide to Treat COVID-19
TFF Pharmaceuticals, Inc. a clinical-stage biopharmaceutical company focused on developing and commercializing innovative drug products based on its patented Thin Film Freezing (TFF) technology platform, announced that it has received approval from Health Canada to begin a Phase 1 clinical trial of a dry powder formulation of niclosamide, an antiviral treatment with potential to address COVID-19 and other infectious diseases.
The Phase 1 study was cleared by Health Canada via a No Objection Letter (NOL) received on October 22, 2021. TFF Pharmaceuticals anticipates the first patient will be dosed in the study in November and that enrollment will be completed by early Q1 2022.
“Early on in the COVID-19 pandemic, niclosamide was identified as a highly promising option for treating severe COVID-19 because of its ability to inhibit cellular processes in the human cell that are required for SARS-CoV-2 replication, thereby inhibiting the production of new viral particles from infected cells,” said Glenn Mattes, CEO of TFF Pharmaceuticals. “Our inhaled niclosamide powder, developed via TFF’s unique Thin Film Freezing technology platform, has been shown to reduce COVID-19 viral load in vivo and offers both direct delivery to the site of infection in the lung and more convenient outpatient administration compared to the IV administered approved antibody COVID-19 treatments. We believe that our preclinical results for inhaled niclosamide will translate to positive outcomes in humans and look forward to initiating the study.”
First approved by the U.S. Food and Drug Administration for use in humans in 1982, niclosamide is an oral anthelmintic drug and is included in the World Health Organization’s list of essential medicines1. It has been used to safely treat millions of patients and was recently shown to exhibit potent antiviral activity against SARS-CoV-22, but has limited water solubility as well as low absorption and oral bioavailability. TFF Pharmaceuticals’ Thin Film Freezing technology enables the development of a dry powder formulation of niclosamide that can be delivered directly to the site of viral replication within the lungs by inhalation and administered to patients in an outpatient setting using a standard dry powder inhaler.
“Inhaled niclosamide presents a potentially game-changing solution to addressing ongoing cases of COVID-19, combining a known potent antiviral against SARS-CoV-2 with TFF’s Thin Film Freezing technology to allow direct delivery to the lungs,” said Jay Peters, M.D., Chief of Pulmonary and Critical Care Medicine at the University of Texas Health Science Center at San Antonio and a member of TFF’s Scientific Advisory Board. “Inhaled niclosamide could also serve as an essential treatment for other infectious diseases that affect the lungs. I look forward to seeing the results of the upcoming clinical trial.”
In June 2021, the Company published in vivo pharmacokinetic data in hamsters and rats showing sufficient lung exposure to achieve an antiviral effect. An accompanying GLP inhalation toxicology study showed no toxicity from the inhaled formulation of niclosamide. Recently, the Company completed an in vivo efficacy study that showed a seven-fold reduction in lung viral load in a hamster model when dry powder niclosamide was administered 24 hours after inoculation with SARS-CoV-2 when the disease was already severe.3
The Phase 1 study will consist of a Single Ascending Dose (SAD) phase with single inhalation doses of 0.5, 2, and 6 mg in three cohorts of healthy volunteers, including six volunteers that will receive active drug and two that will receive placebo; followed by a Multiple Ascending Dose (MAD) phase in which two cohorts of healthy volunteers will receive doses of 3 and 6 mg, respectively, every 12 hours (BID dosing) for five days. Following results from the Phase 1 trial, the next step will be to initiate a Phase 2/3 study in patients with COVID-19. Per an agreement initiated in August 2020, UNION Therapeutics A/S (UNION) has an option to exclusively license the dry powder formulation of niclosamide.
“We find the pre-clinical work by the TFF team encouraging and appreciate that Thin Film Freezing technology may offer an option to improve the delivery of niclosamide. The use of a dry powder inhaler could help to circumvent the poor oral bioavailability and significantly elevate the local exposure in lungs, the primary site of infection,” said Günter Ditzinger, Chief Technology Officer of UNION Therapeutics. “We are looking forward to the results of the Phase 1 program and continuing the partnership with TFF Pharmaceuticals.”