Signifor Earns FDA Approval for Acromegaly

The FDA has approved pasireotide (Signifor long-acting release [LAR], Novartis) injectable suspension for treatment of patients with acromegaly who have had an inadequate response to surgery or for whom surgery is not an option, according to a press release from the manufacturer.

The agency based its approval of the next-generation somatostatin analog on data from two multicenter phase 3 studies — C2305 and C2402.

C2305 was a multicenter, randomized, double blind study in patients with active acromegaly who had not previously been treated with medication and had not responded to surgery or were not eligible for surgery. The researchers randomly assigned patients to pasireotide 40 mg, with a possibility to titrate up to 60 mg, or an active comparator.

After 12 months, the researchers found that a greater percentage of patients in the pasireotide group vs. the active comparator group achieved biochemical control, defined as a mean growth hormone (GH) level <2.5 mcg/L and normal insulin-like growth factor 1 (IGF-1) levels (31.3% vs. 19.2%; P<.01 for treatment difference). About 30% of patients in the pasireotide arm achieved biochemical control early in the study, according to the release.

A significant proportion of the patients treated with pasireotide (98%) experienced a reduction or no change in tumor volume from baseline to month 12. Moreover, reductions in ring size and acromegaly symptom severity scores were observed in both treatment groups.

The most common adverse events with pasireotide vs. the active comparator were diarrhea, cholethiasis, hyperglycemia and diabetes.

C2402 was a randomized study assessing the safety and efficacy of double blind pasireotide 40 mg and 60 mg, as compared with continued open label pre-trial somatostatin analog therapies at maximal or near maximal doses in 198 patients with inadequately controlled acromegaly.

The study met is primary endpoint, with more patients treated with pasireotide 40 mg and 60 mg (15.4% and 20.0%, respectively) achieving biochemical control at 6 months vs. 0% in the pre-trial somatostatin analog therapy control group.

Biochemical control was achieved early in 15.4% and 18.5% of patients treated with pasireotide 40 mg and 60 mg, respectively.

At month 6, a reduction or no change in tumor volume was noted in 81% and 70% of patients treated with pasireotide.

The most common adverse events associated with both pasireotide and pre-trial somatostatin analog therapy were hyperglycemia and diabetes.

“Treating acromegaly can be extremely challenging and the consequences of inadequate normalization of hormone levels can be serious for patients,” Monica Gadelha, MD, PhD, professor at the Federal University of Rio de Janeiro and pivotal trial study author, said in the release.

“With the approval of Signifor LAR, physicians now have a new acromegaly therapy that provides an enhanced mechanism to address elevated hormone levels. This is a significant achievement and much welcomed news for patients with acromegaly.”

Acromegaly is a rare endocrine disorder caused by excess production of GH and IGF-1, usually due to a noncancerous tumor on the pituitary gland. The estimated prevalence of the disease worldwide is 60 cases per million, with an annual incidence of three to four new cases per million.

Though uncommon, acromegaly is associated with a two- to threefold increase in mortality rates and serious health complications like heart disease, diabetes, arthritis and colon cancer.