The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the marketing authorisation of lutetium (¹⁷⁷Lu) oxodotreotide for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults.

The European Commission (EC) will review the CHMP recommendation.

Gastroenteropancreatic neuroendocrine tumours, also known as GEP-NETs, are a group of tumours originating in the neuroendocrine cells of numerous organs.

The estimated incidence of gastrointestinal NETs in the UK is approximately 2.65 per 100,000 per year, while the estimated incidence of pancreatic NETs in the UK is less than 0.2 per 100,000 per year.

However, since NETs are often slow-growing and associated with prolonged survival, the prevalence of NETs is relatively high.

The CHMP adopted its opinion based on results of a randomised pivotal Phase 3 study, NETTER-1 that compared treatment using lutetium (¹⁷⁷Lu) oxodotreotide with a double dose of Octreotide LAR in 229 patients with inoperable midgut NETs progressive under standard Octreotide LAR treatment and overexpressing somatostatin receptors, as well as efficacy and safety data from the Erasmus Phase 1/2 trial conducted in more than 1,200 patients with a wide range of NET indications including bronchial, pancreatic, foregut (excluding bronchial and pancreatic), midgut and hindgut.

The NETTER-1 study met its primary endpoint by demonstrating that treatment with lutetium oxodotreotide was associated with a statistically significant and clinically meaningful risk reduction of 79% in disease progression or death versus a treatment with a double dose of Octreotide LAR (hazard ratio 0.21, 95% CI: 0.13-0.33; p<0.001).

At the time of the data cutoff for the primary analysis, 23 events of disease progression or death had occurred in the lutetium oxodotreotide group and 68 such events had occurred in the control group.

The estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the lutetium oxodotreotide group and 10.8% (95% CI, 3.5 to 23.0) in the control group.

The median progression-free survival had not yet been reached in the lutetium oxodotreotide group and was 8.4 months (95% CI, 5.8 to 9.1) in the control group.

Lutetium oxodotreotide, when administered concomitantly with a renal-protective agent, had low rates of grade three or four haematological toxicity, and no evidence of nephrotoxicity observed over the study time-frame (median follow-up time 14 months).

Martyn Caplin, Professor of gastroenterology and GI neuroendocrinology at the Royal Free London and University College London and Chairman of the European Neuroendocrine Tumour Society, stated, “As a NET specialist, I view lutetium oxodotreotide as a critical tool in my treatment paradigm. Achieving a positive CHMP opinion is the first of several hurdles we have to overcome before this therapy is made widely accessible for patients with progressive disease on current standard of care regimens. This type of therapy has not only demonstrated significant clinical benefit in multiple studies, it is well tolerated and also provides physicians with a treatment option that could be administered in a day case setting, potentially easing the burden on both patients and the health system.”

Lutetium (177Lu) oxodotreotide has received orphan drug designation from the EMA. 

Catherine Bouvier, Chief Executive Officer of NET Patient Foundation, a NET patient advocacy group/charity in the UK, noted, “The NET patient community has been eagerly awaiting the potential approval of this therapy. Given the complex nature of NETs as a disease, there is a limited number of available treatments for people who progress on standard of care. Having access to additional therapies with demonstrated clinical benefit is critical for improving the lives of people living with NETs.”

Source: Advanced Accelerator Applications