Signifor LAR Shows Long-term Benefits for Cushing’s Disease Patients in Phase 3 Extension Trial
Long-term treatment with Signifor LAR, a long-acting formulation of pasireotide, effectively reduced pituitary tumor volume and improved symptoms of Cushing’s disease, results from a Phase 3 extension trial show.
These findings were discussed in the poster, “Long-Term Efficacy and Safety of Once-Monthly Pasireotide in Patients With Cushing’s Disease: a Phase III Extension Study,” presented at the recent 20th European Congress of Endocrinology in Barcelona, Spain.
Sponsored by Novartis, which developed the therapy, the initial Phase 3 trial (NCT01374906) was conducted at 57 clinical sites across 19 countries. It included 150 participants with persistent or recurrent Cushing’s disease who failed to improve after surgery or were unable to have surgery.
Participants were randomized to one of two Signifor LAR doses — 10 mg or 30 mg — injected into the muscle every four weeks. During the trial, doses could be individually adjusted up to a maximum of 40 mg if patients did not have a reduction in their urinary cortisol levels (mUFC).
During the 12-month trial, 41.9% of patients receiving the lower dose and 40.8% of those on the higher dose reached mUFC within normal values.
A once-monthly administration of Signifor LAR had a similar safety profile to a twice-daily injection under the skin of Signifor, a formulation already approved to treat Cushing’s in the U.S. and elsewhere.
After 12 months of treatment, patients whose urinary cortisol levels were back to normal or those who benefited from the treatment could then enter an extension trial where they received the therapy for up to two more years.
A total of 81 patients entered the extension study and remained on their previous dose of Signifor LAR. They received the treatment for a median time of 23.9 months.
At the beginning of the extension trial, 51.9% of patients had mUFC levels within normal range. But the rate of patients with normal cortisol levels kept increasing with their treatment time. At 24 months, 65.5% of patients had normal mUFC levels, and at 36 months, 72.2% did.
Additionally, 13.8% had partial mUFC control at 24 months, which increased to 22.2% at 36 months. Serum cortisol and late-night salivary cortisol levels also decreased throughout the 36 months of treatment, researchers said in a news article.
Researchers also reported a 20% or more reduction in pituitary tumor volume in most patients — 65.8% of patients at 24 months and 64.3% at 36 months.
Long-term treatment with Signifor LAR also improved other symptoms of the disease, including high of blood pressure and body weight.
In general, the treatment was well-tolerated, with no new safety issues reported.
“These data support the use of long-acting pasireotide as an effective long-term treatment for some patients with Cushing’s disease,” the researchers wrote.