Riociguat could help SCD patients with risk factors: Study

Results point to potential for those with PH, kidney disease

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Riociguat, a medication used to treat forms of pulmonary hypertension, was found to safely lower blood pressure in people with sickle cell disease (SCD) who had risk factors for poor outcomes, according to findings from an early clinical trial.

“Our results are encouraging, and open the door to larger clinical trials involving this class of drugs in patients with sickle cell disease who have pulmonary hypertension or kidney disease,” Mark T. Gladwin, MD, professor and dean at the University of Maryland School of Medicine and the study’s first author, said in a university press release.

Having an easy-to-tolerate drug can help patients manage blood pressure and “help prevent serious complications down the road,” added Gladwin, who is also vice president for medical affairs at the University of Maryland, Baltimore.

Trial findings were reported in the study, “Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1–2 trial,” published in The Lancet Hematology. The study was funded by riociguat’s manufacturer, Bayer.

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Risks rise with systemic hypertension

In SCD, red blood cells take on an abnormal, sickle-like shape and become rigid, making it more difficult for them to move through blood vessels. Resultant blood vessel blockages lead to sudden and severe pain attacks, known as vaso-occlusive crises (VOCs).

Impairments in blood flow also leave SCD patients at a higher risk of developing life-threatening conditions, such as kidney failure, heart problems, stroke, or pulmonary hypertension — a condition in which blood pressure in the arteries carrying blood from the heart to the lungs becomes elevated.

The risks associated with these conditions are even higher when a person also has systemic hypertension, or generally high blood pressure throughout the body.

Treatments for pulmonary hypertension work to relax and widen blood vessels, making it easier for blood to flow. They’re thus of interest for helping to prevent these complications in SCD patients.

Previously, scientists tested a pulmonary hypertension medication called sildenafil (sold as Revatio) in SCD patients, but found that it had an unacceptable safety profile. They found that hospital admissions related to pain occurred more frequently in patients given sildenafil than among those given a placebo.

It isn’t yet clear whether this unfavorable safety profile is specific to sildenafil and other therapies in its class — called phosphodiesterase-5 inhibitors — or if it might also be present in other classes of pulmonary hypertension medications.

Riociguat, sold under the brand name Adempas, is another medication used to treat certain forms of pulmonary hypertension, namely pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. It belongs to a class of medications called guanylate cyclase activators.

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Measuring safety

The Phase 1/2 STERIO-SCD trial (NCT02633397) aimed to test the treatment’s safety and preliminary efficacy in adults with SCD who had hypertension, signs of pulmonary hypertension, or high levels of proteins in the urine, an early sign of kidney disease.

A total of 130 patients were randomly assigned to receive oral riociguat or a placebo daily for 12 weeks. The dose was gradually increased to a maximum of 2.5 mg taken three times daily based on a person’s tolerability.

The study’s main goal was to evaluate safety, as measured by the proportion of participants who experienced at least one serious adverse event during treatment or in the week after stopping.

That occurred in nearly a quarter (22.7%) of patients on riociguat, and in 31.3% of those on placebo, with no significant difference between the groups.

There were also no significant differences between the riociguat and placebo groups across key safety outcomes, including pain severity, pain interference in daily life, or SCD-related VOCs.

Eight people on riociguat and seven on placebo required dose reductions, and four from each group stopped treatment due to adverse events. Four deaths occurred, two in each group, none of which was deemed related to treatment.

Side effects associated with the known profile of riociguat, including gastrointestinal events, dizziness, and headache, were not common, and when they did occur, they were not severe, according to the authors.

Patients on riociguat experienced a mean arterial blood pressure decrease of 8.2 millimeters of mercury (mmHg), while those on placebo saw a 1.24 mmHg drop. This 6.96 mmHg difference was found to be statistically significant.

A number of other exploratory endpoints were also evaluated, including those related to exercise capacity, cardiac function, breathlessness, fatigue, kidney function, and blood analyses.

Results showed that certain measures of heart function significantly favored riociguat, but no other endpoints showed a significant difference.

“These findings suggest that the drug riociguat does not have the adverse event profile observed with … sildenafil, and can be safely tested in clinical trials in patients with sickle cell disease,” the researchers wrote.

The researchers recommended that future studies focus on enrolling patients with greater organ and vascular dysfunction or confirmed pulmonary hypertension.