Marc de Garidel
The FDA has assigned a priority review designation to lanreotide (Somatuline Depot) as a treatment for patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), based on findings from the phase III CLARINET study.
As part of this program, the agency plans to take action on the drug's application within 6 months instead of the standard 10 months under regular review, placing the decision date in March 2015. In addition to the FDA, authorities in the European Union are also reviewing lanreotide for patients with GEP-NETs, with a decision expected by the middle of 2015.
The submission for the drug was based on a significant extension in progression-free survival (PFS) with lanreotide compared with placebo for patients enrolled in the CLARINET study. According to results published in The New England Journal of Medicine
, treatment with lanreotide improved PFS by 53% compared with placebo for patients with grade 1 or 2 GEP NETs. Moreover, quality of life was found to be similar between patients treated with the somatostatin analog and placebo.
“We are pleased that the US and European regulatory authorities have accepted the filing for Somatuline in the treatment of GEP-NETs and that the dossier in the US has been granted priority review," Marc de Garidel, the chairman and chief executive officer of Ipsen, the company that developed the drug, said in a press release. "We are excited about the potential benefits Somatuline could bring to patients suffering from this debilitating disease."
The CLARINET study randomized 204 patients to lanreotide at 120 mg (n = 101) or placebo (n = 103). Treatment was administered once a month for 24 months. Patients had tumors that were located in the pancreas (44%), midgut (36%), hindgut (7%), and unknown locations (13%). Most patients had stable disease (96%) and were treatment-naïve (84%). In total, 33% of patients had a hepatic tumor load >25%. The primary endpoint of the study was PFS, with secondary endpoints focused on overall survival (OS) and quality of life.
In the study, the median PFS was not reached with lanreotide versus 18 months with placebo (HR = 0.47; 95% CI, 0.30-0.73; P
<.001). At the end of 24 months, the estimated PFS rate was 65% in the lanreotide arm compared with 33% with placebo.
The HR for PFS in patients with midgut tumors (n = 73) was 0.35 for lanreotide and placebo. Patients with hindgut tumors (n = 14) experienced better PFS outcomes with placebo compared with lanreotide (HR = 1.47). For patients with tumors located in the pancreas (n=91), the HR for PFS was 0.58, favoring lanreotide.
A significant difference in OS was not demonstrated in the trial. There were 19 deaths observed in patients randomized to lanreotide compared with 17 with placebo (P
= .88). After the 24-month study period, patients in the placebo arm were allowed to crossover to receive lanreotide. In total, 47 patients randomized to placebo received lanreotide during the follow-up period.
Treatment with lanreotide was associated with a higher rate of gastrointestinal adverse events. The most commonly observed was diarrhea (26% vs 9%). Other adverse events included hyperglycemia (5% vs 0%) and cholelithiasis (10% vs 3%). For patients who developed cholelithiasis, 4 patients had new gallbladder sludge (3% vs 1%) and 10 patients had new lithiasis (7% vs 3%).
The FDA initially approved lanreotide in 2007 as a long-term treatment for patients with acromegaly. Somatostatin analogs have traditionally been used for symptom control in patients with NETs, although lanreotide is not currently approved for this indication.
“To date, somatostatin analogs are approved to manage symptoms of GEP NETs and are not approved as antitumor therapy," Cynthia Schwalm, president and CEO of Ipsen North America, said in a press release. "Somatuline is the first and only somatostatin analog to demonstrate a statistically significant improvement in progression free survival in GEP NET in a large, multinational study clinical trial."