TFF Pharmaceuticals has wrapped up enrollment in a Phase I trial of its inhaled COVID-19 treatment, putting it on track to report complete safety data by the end of the first quarter.
The study has randomized 40 healthy subjects to receive different dose escalations of TFF’s candidate or placebo. Across a multitude of endpoints, TFF is evaluating outcomes including adverse events, changes in lung function, and pharmacokinetics to determine whether to advance the inhaled therapy.
TFF’s candidate is an inhaled formulation of niclosamide, a molecule used to treat parasitic infections. As researchers searched for molecules effective against SARS-CoV-2 early in the pandemic, a team working out of South Korea found niclosamide worked against the coronavirus in laboratory tests.
“Niclosamide was identified as a highly promising antiviral to treat severe COVID-19 because of its ability to inhibit cellular processes that are required for viral replication. Niclosamide is more potent when compared with other drugs repurposed to treat COVID-19,” said Dale Christensen, head of clinical development at TFF.
The problem, as the South Korean researchers noted at the time, is that niclosamide is poorly absorbed. Earlier studies have shown the molecule has low systemic availability of around 10% when administered orally.
Niclosamide’s poor water solubility is a strength when the molecule is used as an antiparasitic drug. In that context, being able to get a large amount of niclosamide to sites of infection in the gastrointestinal tract, without causing significant systemic absorption, is a positive.
However, poor bioavailability limits the use of niclosamide when systemic absorption is required. TFF has applied its technology to the molecule to try to overcome the limitation and establish niclosamide as a treatment for COVID-19.
“Thin-film freezing technology addresses this issue through convenient self-administration via a pocket-sized inhaler. This delivers the drug directly to the lungs, elevating exposure at the primary site where the SARS-CoV-2 virus replicates while avoiding gastrointestinal side effects and overcoming the absorption limitations of oral administration,” said Christensen.
TFF is well behind the frontrunners in the COVID-19 antiviral space. Gilead Sciences received emergency use authorization for its intravenous antiviral in the US in May 2020, and oral treatments from Merck and Pfizer have since come to market.
Yet, Christensen thinks there remains a need for new COVID-19 drugs, highlighting how TFF’s candidate matches up to the existing treatment options to make his case.
“TFF’s inhaled niclosamide is also positioned to fill gaps of COVID-19 treatment options that have so far been authorized, offering a potentially major advantage compared to remdesivir, which must be infused. It’s also a single agent, compared to Pfizer’s Paxlovid which must be co-administered with ritonavir, and is stable at room temperature, so it can be stored and shipped easily without freezers,” said Christensen.
Union Therapeutics has an option to license the asset and take responsibility for further development following the delivery of Phase I data. Christensen sidestepped questions about the timing of the Union decision and TFF’s plans if its partner walks away, saying only that the two companies “continue to have ongoing joint development meetings to discuss the inhaled niclosamide program and will continue to work together as the program progresses.”