Mezzion Pharma said its investigational drug udenafil improved exercise capacity in adolescents with congenital single ventricle heart disease (SVHD) in a global phase-3 trial.
The latest data did not reach clinical significance in the traditional measurement, which evaluates the maximal oxygen consumption at the subject’s maximal effort (peak VO2), Still, it successfully achieved the oxygen consumption at the ventilatory anaerobic threshold (VO2 at VAT), the company said.
With the findings, Mezzion said it would submit a new drug application (NDA) to the U.S. Food and Drug Administration.
The Kosdaq-listed company unveiled the topline results from the phase-3 study on udenafil for the treatment of SVHD at the Annual Scientific Session of the American Heart Association (AHA) in Philadelphia, the U.S., on Sunday.
Dr. David Goldberg, a pediatric cardiologist at Children’s Hospital of Philadelphia, presented the data in a symposium titled "Fontan Physiology and Results of the FUEL Trial.”
Udenafil aims to improve the heart function and exercise capacity in adolescents who underwent Fontan surgery due to SVHD. The phase-3 FUEL trial evaluated the efficacy and safety of udenafil for 400 patients for six months.
The FUEL study’s primary aim was to improve exercise capacity at the 26th week after treatment, by measuring changes in peak VO2, or the maximal oxygen consumption at the subject’s maximal effort. The results showed that peak VO2 of the udenafil group improved 3.2 percent at the 26th week, compared to the baseline. The outcome showed improvement, compared to 0 percent of the placebo group, but did not reach clinical significance.
However, the findings indicated that VO2 at VAT, which was more appropriate than peak VO2 to measure exercise capacity, showed meaningful improvement in the study, according to Mezzion.
Dr. Stephen Paridon, a pediatric cardiologist and exercise physiologist at Children’s Hospital of Philadelphia, explained that Fontan patients do not have a ventricle to pump the venous blood to the lung and that their blood flow to the lung solely depends on the central venous pressure in the body.
As their central venous pressure is already elevated at baseline, they find it difficult to achieve the full exercise capacity, he went on to say, adding that peak VO2 may not be the best measurement to assess the exercise capacity of Fontan patients.
Rather, VO2 at VAT could be a more relevant measure because the central venous pressure limits it less, he noted.
VO2 at VAT improved by 2.9 percent in the udenafil group compared to a 1.0 percent decline in the placebo group. It was also statistically significant, Mezzion said.
The company had a meeting with the FDA’s cardiovascular and renal division to discuss the topline data of the trial in October.
“The FDA confirmed that Mezzion can proceed with the submission of the NDA for udenafil for improving the exercise capacity of SVHD subjects and that the submission would be ‘fileable’ provided that the submission contained all of the required information,” Mezzion said.
Based on the positive results from the FUEL trial and the safety data on udenafil, the company would expeditiously submit an NDA to the FDA to seek approval for the use of udenafil, it added.