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

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

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.

Ask questions and share your knowledge of PH in our forums.

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.”


  1. Dale W Momenee says:

    When people’s lives ore on the line, facing a terrible death from P.A.H, why do government agencies move like molasses in the winter to get to the step, where clinical trials move from experimentation on rats (which were extremely positive, from my research) to clinical trials on human subjects. I would like to know how to get signed up for a trial (since I don’t have much to loose). I have had this disease for three years now, and it is being treated with 1600mcg of Uptravi, twice a day, and 40mg of Sildenafil, three times a day. My life’s clock, actually started ticking, 5 1/2 years ago when I had pulmonary embolism in my lungs. I started taking Warfarin from that point on, and thought all was O.K. until I started coughing until I vomited along with severe difficulty breathing. I was diagnosed with the disease (in an already advanced state) in February of 2015, and am being treated at Froedtert Hospital in Milwaukee, Wisconsin.

    I am 66 years old and do not qualify for a heart lung block transplant, since I have had prostate cancer, twice in my life (the first time, when I was 45 years old – August 1998 – with a prostate, and the second time 20 months ago with prostate cancer in the bladder neck). Both of my surgeries for prostate cancer were successful, and I never had to have chemotherapy or radiation treatments.

    I would be seriously interested in a clinical trial that you outlined in your above article. It seems to me, it is high time for such a trial.

    • C. Brill says:

      Read your comment and was surprised of some similarities in our cases. I am 55 with IPAH. Been diagnosed two years following a prostate cancer operation (that went well in early stage). I Always had a feeling though that my PAH is somewhat related to the prostate cancer/treatment – medication I got only once called Degarelix (Firmagon). All the doctors I spoke to said there is no relations between these cases. Still not fully convinced. Up until diagnosed have been active in high intensity sports (cycling, racing etc). would definitely be interested in more information regarding this new trial and potential drug.

  2. F. P. Daychee says:

    Like the person above, I would dearly value any information on how to get onto the list for treatment. I am based in England and there is not much support of treatment for this.

Leave a Comment

Your email address will not be published. Required fields are marked *