Clinical Trial Expected in 2019 to Test Therapy C76 as Potential PAH Inhibitor

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by Kara Elam |

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A clinical trial to study a therapy that may inhibit and possibly reverse vascular remodeling in pulmonary arterial hypertension (PAH) is expected to start enrolling patients in 2019. The medicine, C76, was shown to inhibit a gene called HIF-2α and to lead to reversal of PAH in animal models.

The study reporting the findings, “Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in PAH with HIF-2α Inhibitor,” was published in the American Journal of Respiratory Critical Care Medicine.

Earlier this year, scientists at Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago published a study showing that a gene called FoxM1 was an important regulator of vascular remodeling, a process involved in pulmonary hypertension that can lead to right-sided heart failure.

The activity of FoxM1 is regulated by another factor called HIF-2α (hypoxia-inducible factor-2α), which also has been shown to promote vascular remodeling.

Now, the same lead researchers at Lurie Children’s Hospital conducted a study to assess whether blocking HIF-2α with a selective inhibitor could reverse PAH and right heart failure in different rodent models of the disease.

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The team used the drug C76, a HIF-2α inhibitor. Overall, they found that the inhibitor reduced the animals’ right ventricle systolic pressure and right ventricle hypertrophy, suppressed vascular remodeling, prevented right heart failure, and increased the survival of the animals.

C76 also was determined to be safe and well-tolerated by the animals.

Based on those positive results, the team is planning to test the HIF-2α inhibitor in humans in 2019.

“We are thrilled to reach this critical stage in developing the first drug for pulmonary arterial hypertension that targets the mechanisms behind disease development,” Zhiyu Dai, PhD, said in a press release. Dai is with the Manne Research Institute at Lurie Children’s, and also assistant professor of Pediatrics at Northwestern University Feinberg School of Medicine.

“We plan to complete preclinical testing of the new drug by the end of 2018 and launch a clinical trial in 2019,” Dai said.

Youyang Zhao, PhD, the study’s senior author and program director, added: “It is exciting to see our research progressing from the bench to the bedside … Now we have a promising drug that we know is safe to test in a clinical trial. We are hopeful that it can reverse vascular remodeling in patients with this devastating disease and ultimately save lives.”

A Conversation With Rare Disease Advocates