TFF Pharmaceuticals, a clinical-stage biopharmaceutical company specializing in the development and commercialization of drug products using its thin-film freezing (TFF) platform, has announced safety and pharmacokinetic (PK) data from its Phase I trial of niclosamide inhalation powder, intended to treat COVID-19.
To learn more about niclosamide, the study, and what might be next, Outsourcing-Pharma connected with Dale Christensen, TFF Pharmaceuticals' head of clinical development.
OSP: Could you please share your perspective on the discovery and development of COVID-19 treatments since the virus landed on us?
DC: The pharmaceutical and healthcare industries have been working tirelessly to discover and develop vaccines and treatments for COVID-19 since the virus first began in 2020. Great strides have been made, including the approval of multiple effective vaccines and therapeutics, but there is still an ongoing unmet need for safe and effective treatments that are resistant to variant drift.
A potent antiviral like niclosamide could represent a much-needed solution but faces challenges because when it is administered orally since the drug doesn’t reach the lungs where the virus is replicating. That’s where our TFF technology and its ability to convert antiviral therapies like niclosamide to inhaled treatments come in. We deliver the antiviral to the site of the infection.
OSP: Specifically, what do you think have been some of the challenges, successes, bright spots, and stumbling blocks in the path to come up with effective treatments?
DC: The industry-wide collaboration to discover, develop and scale up effective vaccines and therapies has been extremely impressive and has benefited billions of people. However, the emergence of new variants that reduce the effectiveness of both approved treatments and therapies in development has been frustrating and has limited accessibility and progress.
Furthermore, current vaccines are less effective for certain populations, such as immunocompromised patients. As we look toward the future of therapies for COVID-19, we need to not only be prepared to address current variants but to look ahead to future variants and challenges that may arise and have the resources in place to address those challenges quickly. We also need to ensure we have a broad range of treatments that can benefit all patients and people at risk of COVID-19.
OSP: Please tell us about your niclosamide treatment, and how it’s progressed up to now.
DC: Over the past several months we have progressed through our Phase I study of niclosamide inhalation powder to treat COVID-19, which completed enrollment in January. In parallel, as part of our ongoing commitment to ensuring that the treatment remains relevant, we conducted ongoing preclinical studies to determine its effectiveness against current variants, and in February we reported positive data indicating that niclosamide inhalation powder significantly inhibits viral replication of the Omicron variant.
Most recently, in April, we reported the safety and pharmacokinetic data from the Phase I study. The results indicate that niclosamide inhalation powder is well tolerated with no serious adverse events occurring in the study and this supports a dose of 12mg daily (6mg administered twice a day) for progression into Phase II testing. A 6mg dose level of Niclosamide Inhalation Powder is estimated to produce a concentration of >100 μM in the epithelial lining fluid of the lung.
Furthermore, this low dose provided essentially the same maximum drug concentration in the blood as the 100 mg dose delivered as a nebulized spray to the lungs and nasal cavity, suggesting the dry powder inhaled formulation is very efficiently delivered compared to other therapeutic options.
OSP: Could you please share why niclosamide’s progress is good news for the COVID-weary public?
DC: The main limitations of the current landscape of COVID-19 treatments are reduced activity against emerging variants and limited global accessibility. Niclosamide inhalation powder has the potential to address both of those challenges through the use of an antiviral that is variant-resistant and easy administration through a standard inhaler, which also enables easier transport by eliminating the need for cold-chain refrigeration.
We look forward to continuing to explore inhaled niclosamide as a potentially safe and effective treatment for COVID-19 that can benefit patients around the world and reduce the ongoing threats posed by COVID-19.
OSP: Do you have anything to add?
DC: In addition to inhaled niclosamide, our pipeline includes other programs to address COVID-19 and other diseases, including our inhaled formulation of voriconazole which continues to progress through clinical studies to address Invasive Pulmonary Aspergillosis (IPA) and other fungal diseases. We look forward to continuing to share updates on the progress of TFF’s programs and the potential of thin-film freezing technology to streamline drug development and positively impact patients.