Data from an ongoing real-world study show that treatment with Signifor (pasireotide) is able to normalize cortisol levels for sustained periods in patients with Cushing’s disease for whom surgery has failed or is not an option.
Half of the new Signifor users reached normal cortisol levels one month after starting treatment, and maintained it for up to nine months. A few prior users of the medicine still had normal cortisol levels three years after.
The findings were reported in the study, “Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing’s disease: interim results from a long-term real-world evidence study,” and published in the journal Pituitary.
Novartis’ Signifor is the first medicine specifically approved for adults with Cushing’s disease who are not eligible for surgery or have experienced relapses after surgery. Recordati recently acquired global rights over the medicine.
Prior clinical trials have supported the favorable efficacy and safety profile of the medicine. But real-world studies that bring forth its long-term benefits and risks in real clinical practice are still needed.
To address that, Novartis set up a global post-marketing study (NCT02310269), primarily to evaluate the long-term safety and efficacy of Signifor, administered in routine clinical practice in adult patients who failed or could not have surgery.
Signifor was given as subcutaneous (under the skin) injections, alone or in combination with other therapies. Each enrolled patient was followed for up to three years.
Participants either initiated treatment with Signifor at study entry (new users) or had started treatment before and continued through the study (prior users).
At the time of this interim analysis, 127 patients were included — 31 new users and 96 prior users. Their mean age was approximately 50 years. Among prior users, eight patients completed the 3-year follow-up, 53 were still on treatment, and 66 had withdrawn.
The median duration of treatment was 3.4 months for new users and 30.5 months for prior users, including prior treatment not included in the study period.
New users and prior users experienced a total of 24 (77%) and 37 (40%) treatment-related adverse events. Most adverse events were mild to moderate (70%) and were consistent with the known safety profile of Signifor.
The most common unwanted effects were nausea (14%), high blood sugar, or hyperglycemia (11%) and diarrhea (11%). Effects related to hyperglycemia — frequently observed in studies of Signifor — were reported in 23.6% of the patients.
The medicine leads to increases in sugar (glucose) by suppressing insulin secretion. This effect is reversible upon treatment discontinuation, according to the authors.
Prior users experienced fewer adverse events, which could be because patients who tolerated Signifor were more likely to continue on treatment, but it could also reflect a gain of tolerance over time, namely to gastrointestinal effects such as nausea and diarrhea.
Overall, 24 of 123 patients (19.5%) discontinued the study because of a treatment-related adverse event. No deaths were attributed to Signifor use.
In a previous Phase 3 clinical trial (NCT00434148), Signifor yielded rapid and sustained reductions and normalized the levels of mean urinary free cortisol (mUFC) in about 20% of enrolled patients at six and 12 months.
Here, 50% of the patients starting Signifor for the first time achieved normal cortisol levels within the first month of treatment. This is a high response rate, researchers say, and was maintained for up to nine months. Later responses could not be determined because of the lack of available measurements.
Long-term control of cortisol levels was further demonstrated in patients who had been receiving the medicine prior to the study’s start: 65% of these patients had normal cortisol at study start, and this proportion was maintained over time — 82% after one additional year of treatment, and 67% after two years of treatment.
Two patients for whom measurements were available still had normal cortisol levels at the end of the 3-year follow-up.
Researchers say these results support “the favorable long-term benefit-risk profile of pasireotide in patients with [Cushing’s disease]” and confirm prior results from an extension study.
Researchers cautioned, however, that “response rates may be overstated as patients who discontinued treatment because of an unsatisfactory therapeutic effect … were not included in the analyses.”
The study is still active and recruiting patients in the United States, Canada, Europe, Colombia, Israel, and Lebanon. For more information about contacts and locations, go to the official webpage.