Advanced Accelerator Applications

The company's lead product is LUTATHERA, a Lutetium Lu 177 dotatate labeled somatostatin analogue peptide,[9] a theragnostic cancer product being developed to treat certain gastro-entero pancreatic neuroendocrine tumors (GEP-NETs).[10] It selectively targets over-expressed somatostatin receptors while also giving off gamma emissions to allow physicians to visualize where in the body both the drug and the tumor are. It was approved by the FDA in January 2018 for GEP-NET.[11]

Lutathera, also known as lutetium Lu 177 dotatate, is a target treatment drug for patients with GEP-NETs.[12] Its approval for Advanced Accelerator Applications was announced on January 26, 2018, by the US Food and Drug Administration.[13] Lutathera is most notable as the first FDA approved peptide receptor radionuclide therapy (PRRT) to combat GEP-NETs.[14]

GEP-NETs are rare groups of cancer that continue to proliferate, regardless of initial therapy treatments.[12] They are present in areas affected by pancreatic or gastrointestinal cancers; specifically, the pancreas, stomach, intestines, colon and rectum.[13]

Lutathera is used to combat pancreatic and gastrointestinal cancers that do not respond well to common chemotherapeutical treatments; namely for patients with somatostatin receptor-positive GEP-NETs.[12][13] These receptors are commonly found on tumors located in the foregut, midgut, and hindgut.[15]

Lutathera is a radioactive drug consisting of a tyrosine-containing somatostatin analog Tyr3-octreotate (TATE) attached to the chelating agent tetraazacyclododecanetetra-acetic acid (DOTA).[16] Attached to the dotatate is the radioactive marker Lu-177, a radioisotope.[12] The dotatate binds to the GEP-NET positive somatostatin receptor cells commonly present on neuroendocrine tumors.[12][16] After binding to the receptor, Lutathera enters the cell and uses its radioactive property to damage DNA.[12] This mechanism effectively triggers apoptosis of cancerous tumor cells. As a result, studies found that 16% of patients being treated with Lutathera experienced either complete or partial tumor shrinkage.[12]

FDA approval of Lutathera was ultimately supported by two clinical studies.[13] NETTER-1, a Phase 3 study, was a randomized clinical trial which included patients with a severe form of somatostatin receptor-positive NETs.[12][14] The study compared Lutathera treatment with a standard dose of octreotided LAR against a high-dose of octreotide LAR.[12] Researchers measured tumor growth after the course of the treatment, also known as progression-free survival.[13] The study concluded that patients who were treated with Lutathera lived substantially longer compared to those who only received the octreotide treatment.[12] They experienced a 79% reduction in death and cancer progression.[14]

The Netherlands study gathered several patients with somatostatin receptor-positive tumors, including patients with GEP-NETs.[12] The study found that 16% of patients with GEP-NETs, who were treated with Lutathera, experienced complete or partial tumor shrinkage.[12] As a result, a pre-planned interim overall survival analysis found that Lutathera treatment lead to a 48% reduction in risk of death.[14]

[12][13][14][15]

Lutathera is a major technological advancement for the detection of tumors. Diagnostic imaging that relies on dotatates can now rely on Lutathera to locate somatostatin receptor-positive tumors by tagging them with its radioactive component.[12] This tagging of tumors will allow them to become more visible during positron emission tomography (PET) scans.[12] With LU-177 dotatates, more somatostatin receptor-positive GEP-NET patients can be identified for treatment of the disease.[12]