Tenax Cleared by FDA to Begin Clinical Trials for PAH of Oral Imatinib

The United States Food and Drug Administration (FDA) has cleared Therapeutic Tenax to begin clinical testing of its new oral formulation of imatinib in people with pulmonary arterial hypertension (PAH).

The company plans to conduct a small pharmacological study this year and then launch a Phase 3 clinical trial by June 2022 to test the effectiveness of the therapy.

“Tenax is delighted that we can now advance our imatinib HTAP program to pivotal testing,” said Christopher Giordano, CEO of Tenax, in a Press release. “We remain on track to be the first company to begin a Phase 3 trial of a new formulation of imatinib in patients with PAH. “

Imatinib is a small molecule that blocks the activity of signaling proteins in the body that are involved in the growth of certain types of cells.

An oral formulation of imatinib – 100 mg and 400 mg tablets, marketed as Gleevec through Novartis – is approved to treat certain types of blood cancers, in which the growth of cancer cells is driven by these signaling molecules. These signals are also believed to contribute to the abnormal growth of blood vessel cells that occurs in PAH, which forms the theoretical basis for the use of imatinib in PAH.

“Imatinib has been shown to block several growth factors that regulate endothelial and vascular smooth muscle cell proliferation in PAH,” said Stuart Rich, MD, medical director of Tenax.

Novartis conducted clinical trials testing the original formulation in patients with PAH in the early 2010s. results reported that the treatment improved certain characteristics of blood flow, as well as ability to exercise. However, the drug had a poor safety and tolerability profile, which led many trial participants to discontinue treatment. Gastrointestinal problems, including nausea and vomiting, were particularly common.

Ultimately, Novartis halted the development of imatinib for PAH, deciding that the safety concerns outweighed any potential benefit.

The imatinib formulation that Tenax is currently developing is intended for oral use, like the original formulation from Novartis. However, it’s been specially designed to avoid irritating the digestive tract, which the company says will lead to fewer safety concerns.

“A suboptimal oral formulation of the drug [imatinib] has limited its therapeutic utility in PAH. The reformulation of Tenax from imatinib directly addresses this problem, ”said Rich.

“We expect our formulation to be the first drug therapy to conclusively show a disease modifying impact, due to the inhibition of pulmonary vascular remodeling observed in PAH,” he said.

Tenax is now planning to launch a small clinical trial that will compare the pharmacological properties of its new formulation of imatinib to the original version from Novartis. The company hopes to get results by the end of this year and hopes to begin phase 3 clinical trials in the second quarter of 2022.

“The efficacy of imatinib has already been clinically proven in PAH, and with our unique formulation, we anticipate a better tolerated, and therefore more effective, treatment option with the potential to advance the current standard of care.” , said Giordano.

It should be noted that Tenax acquired PH Precision Med, the original developer of the new formulation, earlier this year.

An inhaled formulation of imatinib, called AER-901, is currently under development for PAH by Aerami Therapeutics. Clinical trials began earlier this year.

These two investigational formulations of imatinib have received orphan drug designation by the FDA. The designation gives certain advantages to the developer of a therapy, with the aim of inducing companies to develop treatments for rare diseases.