Adempas helps lower risk in PAH patients, newer risk model confirms
COMPERA 2.0 analyses support drop in mid-level death risk with therapy
People with pulmonary arterial hypertension (PAH) seen to be at an intermediate risk of death — whether in the low or high range of that middle-level risk — were more likely to have better outcomes when treated with Adempas (riociguat) than given a placebo in a Phase 3 clinical trial, its data show.
“This analysis supports the risk-reduction benefits of [Adempas] in patients with PAH at intermediate-low risk and intermediate-high risk,” wrote the researchers. They also showed that a risk model called COMPERA 2.0 can be used to predict long-term outcomes in clinical testing.
The analysis, “Riociguat in pulmonary arterial hypertension: Application of the 4-strata COMPERA 2.0 risk assessment tool in the PATENT studies,” was published in the journal Respiratory Medicine. It was funded by Bayer, which markets Adempas, and by MSD, known as Merck in the U.S. and Canada.
Adempas works to relax and widen blood vessels in the lungs
In PAH, a narrowing of blood vessels of the lungs causes high blood pressure in the vessels taking blood from the heart and reduces the blood flow to the lungs. As a result, a lesser amount of oxygen is available in the blood in the lungs, causing shortness of breath and making exercise difficult.
The active ingredient in Adempas, riociguat (available as a generic), activates an enzyme called soluble guanylate cyclase in these blood vessels, helping them to relax and widen. This lowers blood pressure in the lungs and improves exercise capacity.
Risk assessment can be used to estimate the likelihood that a person’s PAH symptoms will worsen, helping to guide doctors in treatment decisions. The COMPERA 2.0 risk model, in particular, assesses the risk of death within one year. It divides patients into four groups, or strata, based on clinical factors. Introduced in 2022, this model possibly gives a more precise measure of risk than the earlier, three-strata COMPERA model recommended when assessing PAH.
Researchers led by those in Germany used the four-strata COMPERA 2.0 risk model to analyze data from the placebo-controlled Phase 3 PATENT-1 (NCT00810693) clinical trial, which formed the basis for Adempas’ approval, and its long-term extension study, PATENT-2 (NCT00863681).
They compared the risk groups at baseline (the start of PATENT-1) and after 12 weeks, and looked at how these strata predicted long-term outcomes, such as time to clinical worsening and survival after two years in the PATENT-2 clinical trial.
Risk assessment upgraded for more trial patients on Adempas than placebo
At baseline, COMPERA 2.0 strata were available for 214 patients on Adempas and 100 on the placebo. About half of these people were at intermediate-low risk, with similar percentages in the Adempas and placebo groups (48% vs. 50%). Next came the intermediate-high stratum, also with similar percentages between the treatment and control groups (27% vs. 29%).
Over 12 weeks, a higher percentage of Adempas-treated patients lowered their risk stratum (24.8% vs. 15.9%) and were classified as being at low risk of death (44% vs. 27%). Patients on Adempas also walked farther on the six-minute walk test (6MWD), a measure of exercise capacity.
“Similar to the overall PATENT-1 population, larger changes in 6MWD were seen with riociguat vs placebo in both intermediate-low and intermediate-high risk groups,” the investigators wrote.
When the researchers looked across the intermediate risk group, they observed that a higher percentage of patients improved their risk status with Adempas compared with the placebo in the intermediate-low (38% vs. 22%) and intermediate-high strata (42% vs. 31%).
“At PATENT-1 baseline, approximately one-half and one-third of patients were at intermediate-low and intermediate-high risk, respectively. [Adempas] improved COMPERA 2.0 risk strata vs placebo overall,” the researchers wrote.
The COMPERA 2.0 risk model, both at baseline and week 12, predicted survival and clinical worsening at two years in PATENT-2, validating “the utility of COMPERA 2.0 in the long-term risk assessment of patients from a clinical trial population,” the scientists wrote.
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