UMSOM Researchers Identify Safety of a Potential New Treatment to Manage Complications from Sickle Cell Disease

Treatment for lung condition could help patients with sickle cell disease control complications from hypertension and kidney damage

A drug approved to treat pulmonary arterial hypertension may be effective at managing hypertension and end-organ damage in patients with sickle cell disease, according to a new study published in Lancet Haematology. An early phase randomized clinical trial involving 130 patients with sickle cell disease found that the drug, called riociguat, was found to be safe to use and well tolerated in these patients and significantly improved their blood pressure. Preliminary efficacy data suggested the medication might improve heart function.

An estimated 100,000 Americans have sickle cell disease, and the disease occurs in about 1 out of every 365 Black or African-American births, according to the Centers for Disease Control and Prevention. People with sickle cell disease are at high risk for vascular complications that can lead to pulmonary hypertension, stroke, and kidney failure as well as severe pain when red blood cells block blood flow through tiny blood vessels in the chest, abdomen, and joints. These complications can be worsened by hypertension.

Unfortunately, previous research found that sildenafil, an effective treatment for pulmonary hypertension, caused unacceptable side effects in patients with sickle cell disease. It found that those who took this drug experienced high levels of pain that caused increased admissions to the hospital compared to those who took a placebo treatment.

This new study was designed to test the safety of riociguat and how well it works in preventing or reducing the clinical complications for patients with sickle cell disease.

In the study, patients with sickle cell disease and mild hypertension or protein in their urine (an early sign of kidney disease) were randomly assigned to receive either riociguat or a placebo in a double-blind clinical trial. Both groups received the study drug at a starting dose of 1 milligram, which was gradually increased up to 2.5 milligram, taken three times a day for 12 weeks. The researchers found that among the participants who took riociguat, 22.7 percent experienced at least one serious adverse event related to the treatment. In comparison, in the group that received the placebo, 31.3 percent of participants had at least one serious adverse event during the study.

The differences were not statistically significant. There were no differences between the two groups in the rates of pain severity, pain interference in their daily lives, and in vascular events related to their sickle cell disease. When it comes to the effectiveness of the drug treatment, participants who took riociguat had their blood pressure drop by 8.20 mmHg, while those who took a placebo only saw a decrease of about 1.24 mmHg. The result was highly statistically significant, meaning riociguat was much more effective at lowering blood pressure compared to the placebo, with a difference of approximately 6.96 mmHg. In summary, riociguat was found to be safe and led to a significant improvement of blood pressure over the duration of the study.

“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. Having a drug that’s easy to tolerate can help them better manage their blood pressure and help prevent serious complications down the road,” said study leader Mark T. Gladwin, MD,  who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore.

Bayer Pharmaceuticals, manufacturer of riociguat, provided funding (as well as the drug and placebo) for the study.

The study was led by the clinical and data coordinating centers at the University of Pittsburgh. Study co-authors included faculty from the University of Illinois at Chicago, Albert Einstein College of Medicine, University of Pittsburgh, Emory University, Duke University, Johns Hopkins School of Medicine, and other institutions.

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Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.2 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System ("University of Maryland Medicine") has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational  medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu.