Isturisa may help control diabetes, hypertension in Cushing’s disease
Long-term treatment shown to lower blood pressure, sugar in patients
Long-term treatment with Isturisa (osilodrostat) may help lower blood pressure, and blood sugar, levels in people with Cushing’s disease who have high blood pressure, also known as hypertension, or diabetes, according to a new analysis.
Use of the approved medication for up to 1.4 years helped to ease hypertension and control diabetes in Cushing’s disease patients involved in two global Phase 3 clinical trials, the analysis found.
“[Co-occurring] hypertension and diabetes improved in many patients with Cushing’s disease during long-term [Isturisa] therapy, with many patients able to stop/reduce the dose of antihypertensive or antihyperglycemic medications,” the researchers wrote.
The data indicate that Isturisa “effectively controls [high cortisol levels], leading to improved clinical signs, and may reduce treatment burden associated with [co-occurring conditions] in patients with Cushing’s disease,” the team wrote.
The study, “Osilodrostat improves blood pressure and glycemic control in patients with Cushing’s disease: a pooled analysis of LINC 3 and LINC 4 studies,” was published in the journal Pituitary. The work was funded by Novartis, Isturisa’s original developer, and by Recordati, which now markets the therapy.
Investigating the effects of Isturisa on blood pressure, blood sugar
In Cushing’s disease, a tumor in the brain’s pituitary gland leads to the excessive production of adrenocorticotropic hormone, known as ACTH, which in turn stimulates the adrenal glands atop the kidneys to produce excessively high levels of the hormone cortisol. Elevated cortisol levels drive Cushing’s disease symptoms and other health problems. Such problems, which often include high blood pressure and blood sugar dysregulation, can set the stage for diabetes and hypertension.
Isturisa is an oral therapy approved in the U.S. and Japan, and in the European Union, to treat Cushing’s disease in patients for whom surgery to remove the disease-driving tumor is not an option or is not effective. It works by inhibiting an enzyme involved in cortisol production.
The therapy had been tested in two Phase 3 clinical trials: LINC-3 (NCT02180217), completed in 2019, and LINC-4 (NCT02697734), which wrapped up in 2020. Isturisa won U.S. regulatory approval in 2020.
Now, an international team of researchers sought to evaluate how Isturisa affects blood pressure and blood sugar levels in Cushing’s disease patients. To that end, the researchers conducted a pooled analysis of data from 210 patients involved in those clinical trials.
“This is the largest prospective analysis of long-term changes in blood pressure, glycemia [blood sugar], and clinical parameters in patients with Cushing’s disease receiving long-term medical therapy,” the researchers wrote.
Before receiving Isturisa, more than 80% of the patients had hypertension and 40% had diabetes.
Many patients were able to reduce use of other medications
Among patients who had hypertension before starting treatment, more than half saw their blood pressure drop to a normal range after 12 weeks, or about three months, on Isturisa, the analysis found. In most of these individuals, blood pressure remained within a normal range out to more than a year on the therapy.
Importantly, per the researchers, the use of medications to control high blood pressure among these patients also declined over time.
“Blood pressure improved during [Isturisa] treatment; reductions in mean [blood pressure] were observed by [week 12] and were maintained over long-term (72 weeks) treatment,” the researchers wrote.
In patients who did not have hypertension before starting on Isturisa, blood pressure measurements remained generally stable with long-term treatment. A handful of participants who did not have hypertension at the study’s start developed it after starting Isturisa therapy. Statistical analyses showed a weak association between decreases in blood pressure and changes in urinary cortisol levels over time.
Sustained control of cortisol levels [with Isturisa] led to rapid improvements in blood pressure and [blood sugar] parameters in patients with hypertension and diabetes at [the studies’ start].
According to the researchers, “these data demonstrate that rapid and sustained control of cortisol can improve [co-occurring] hypertension during long-term [Isturisa] treatment in patients with Cushing’s disease.”
In patients who had diabetes, mean blood sugar levels decreased with long-term Isturisa therapy. In individuals without diabetes, blood sugar levels remained stable, with a small number of participants seeing increases while on Isturisa. Similar to the findings for blood pressure, data suggested that a more pronounced decrease in cortisol levels was associated with greater reductions in blood sugar.
Additionally, some patients were able to lower the dose or stop taking medicines to control blood sugar after long-term treatment with Isturisa.
“Sustained control of cortisol levels led to rapid improvements in blood pressure and glycemic parameters in patients with hypertension and diabetes at [the study’s start],” the researchers wrote, noting that neither blood pressure nor blood sugar showed a significant association with changes in patients’ weight.
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