New Data Support Long-term Efficacy, Safety of Isturisa

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Isturisa | Cushing's Disease News | LINC-3 clinical trial | clinical trials illustration

Treatment with Isturisa (osilodrostat) normalized urine cortisol levels up to nearly 1.5 years in people with Cushing’s disease, according to data from the Phase 3 LINC-4 clinical trial.

Data from another Phase 3 trial, LINC-3 (NCT02180217), showed that testosterone levels were generally stable among Cushing’s patients treated with Isturisa, and real-world data from another study showed no new safety issues related to the treatment.

These findings were shared by Recordati Rare Diseases, which markets Isturisa, across three presentations at the annual ENDO 2022 meeting June 11–14 in Atlanta.

“The data from these studies reinforces the efficacy and safety of Isturisa as a treatment for patients with Cushing’s disease,” Mohamed Ladha, president and general manager of North American business at Recordati, said in a press release.

“We are pleased to share these data with the endocrine community and are excited to provide patients with a much-needed step forward in the management of this rare, debilitating, and potentially life-threatening condition,” added Ladha.

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Cushing’s disease is characterized by abnormally high levels of the stress hormone cortisol, which ultimately cause the disease’s symptoms. Isturisa is an approved Cushing’s treatment that works by blocking cortisol production.

In the LINC-4 clinical trial (NCT02697734), people with persistent or recurrent Cushing’s disease were given Isturisa or a placebo for 12 weeks. All participants then were treated with Isturisa for up to 72 weeks (nearly 1.5 years).

Previous data showed the trial met its main goal, with a significantly higher proportion of patients treated with Isturisa achieving normal urinary cortisol levels after 12 weeks compared with those given a placebo (77% vs. 8%).

Data presented at ENDO 2022 showed that at week 48, 50 of 73 patients (68.5%) had normal urinary cortisol levels. At week 72, urinary cortisol levels were normal in 40 of 65 evaluable participants (61.5%).

The most common side effects reported during the trial included decreased appetite (46.6%), joint pain (45.2%), fatigue (39.7%), nausea (37.0%), headache (34.2%), and dizziness (30.1%).

LINC-3 enrolled 137 people with Cushing’s disease. All participants were given Isturisa, with some briefly switching to a placebo during the trial’s first year. Previous data from LINC-3 showed that Isturisa was well-tolerated, and able to rapidly and sustainably lower urine cortisol levels.

At ENDO 2022, researchers presented findings about how the treatment altered testosterone levels over a median Isturisa exposure time of nearly 2.5 years.

Results showed that testosterone levels increased somewhat after patients started treatment with Isturisa. With continued treatment, testosterone levels stabilized in males and dropped in females. Only two participants discontinued treatment due to hormone-related side effects.

Among female participants with available data, scores on hirsutism — unusually dark, coarse body hair, often related to high testosterone levels — either were stable or improved in 63  of 76 patients (83%) at week 48, and in 55 of 64 patients (86%) at week 72.

A final presentation at ENDO 2022 focused on data from 42 patients with endogenous Cushing’s syndrome, including 34 with Cushing’s disease, who were treated with Isturisa in a real-world study called ILLUSTRATE.

About two-thirds of Cushing’s disease patients included in the analysis were started on a dose similar to that used in clinical trials.

Results revealed no new safety findings, and high treatment persistence (95.8%) among patients who enrolled in the study at least six months prior to its end. Data from ILLUSTRATE also demonstrated that, in agreement with previous studies, patients in whom treatment doses were gradually upped over a long period of time tended to show higher treatment persistence.