On September 15, Tenax Therapeutics announced a delay in the initiation of the Phase III clinical trial for its oral imatinib drug, TNX-201, for pulmonary arterial hypertension (PAH). The estimated date has shifted from H2 2022 to 2023 as part of a strategic evaluation of the company’s financial resources. This is good news for Tenax’s main competitor, Aerovate, which has an ongoing Phase IIb/III trial for dry powder inhalation imatinib, AV-101. Both formulations have received orphan drug designation from the FDA and hold the potential to become the first-in-class tyrosine kinase inhibitor (TKI) drug for PAH.

PAH is characterized by abnormal pulmonary vascular remodeling and vasoconstriction. One highly unmet need in the PAH space is the absence of disease-modifying therapies targeting vascular remodeling. Currently marketed PAH drugs—including endothelin receptor antagonists, PDE5 inhibitors, soluble guanylyl cyclase stimulators, and prostacyclin derivatives—promote vasodilation or prevent vasoconstriction, but do not alter disease progression. Imatinib targets a novel pathway by blocking the activation of the tyrosine kinase receptor PDGFR to inhibit vascular remodeling. Oral imatinib is currently marketed globally for several oncogenic indications by Novartis under the brand name Gleevec in the US. After showing promise in animal studies, Novartis investigated oral imatinib as a repurposed drug for PAH in the IMPRES Phase III trial. Results from the trial published in 2013 showed a significant improvement in exercise capacity and vascular resistance in PAH patients over 24 weeks compared to placebo. However, reports of serious adverse events in 44% of patients and high discontinuation rates (33%) prompted the FDA to request further trials to assess its safety before approval. Subsequently, Novartis discontinued investigating oral imatinib for PAH.

Tenax expects that its reformulated oral imatinib, TNX-201, will reduce the incidence of serious adverse events, specifically gastric intolerance. However, key opinion leaders (KOLs) interviewed by GlobalData have stated that Aerovate’s inhalation imatinib, AV-101, will hold more potential if it maintains efficacy in Phase III trials, due to its improved safety profile. Phase I safety data shows reduced systemic exposure of the inhalation drug, and Aerovate believes this will improve the benefit-to-risk ratio over oral imatinib. Phase IIb/III clinical trials of AV-101 were initiated in 2021 (IMPAHCT-FUL) and have an expected completion date in 2025. If successful, GlobalData forecasts that AV-101 will launch in 2027, one year prior to the launch of TNX-201. Following the delay of Tenax’s TNX-201 Phase III initiation, AV-101 now holds an even stronger competitive advantage as the first-in-class TKI for PAH.