Novartis' Bet Pays Off as Advanced Accelerator Applications Wins FDA Nod for Lutathera

 Advanced Accelerator Applications (NASDAQ:AAAP) (AAA or the Company), a Novartis company and leader in nuclear medicine theragnostics, today announced that  it has received US Food and Drug Administration (FDA) approval of its new drug application (NDA) for LUTATHERA^® (lutetium Lu 177 dotatate*) for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. LUTATHERA^®, which received orphan drug designation from the FDA, is a first-in-class drug and the first available FDA-approved Peptide Receptor Radionuclide Therapy (PRRT), a form of targeted treatment comprising a targeting molecule that carries a radioactive component.

NETs are rare tumors originating in the neuroendocrine cells of numerous organs, including the gastrointestinal tract, pancreas and lung. Some patients develop symptoms arising from the excessive production of hormones by neuroendocrine tumor cells, while others remain clinically silent for years. The estimated incidence, or rate of new cases of NETs, in the United States is approximately 6.98/100,000 per year, while the estimated prevalence for 2014, based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, was 171,321.¹ Patient survival with advanced GEP-NETs depends on stage and histology. Patients with well- and moderately-differentiated tumors and distant metastases have a 5-year survival probability of 35%.²

"The approval of LUTATHERA^® marks an important achievement and innovation for the NET community," said Susanne Schaffert, PhD, Chairperson and President of Advanced Accelerator Applications. "As the first PRRT ever approved in the US, LUTATHERA^® is introducing a major advancement in the treatment paradigm for these patients that we hope will improve many lives. We believe nuclear medicine has the potential to offer many benefits to cancer patients and will use this approval as a foundation for the development of additional targeted cancer treatments utilizing radiolabeled ligands."

Stefano Buono, Advisor and former Chief Executive Officer of Advanced Accelerator Applications, stated, "The approval of LUTATHERA^® is the culmination of years of hard work and partnership with numerous physicians and patients. With this approval, AAA’s first theragnostic pairing, based on radiolabeling the same targeting molecule with either lutetium 177 or gallium 68, respectively for therapeutic or diagnostic purposes is complete. The theragnostic complement to LUTATHERA^® in the US is another first-in-class drug, NETSPOT^®(gallium Ga 68 dotatate) which was approved by the FDA for localization of NETs using Positron Emission Tomography (PET) in 2016."

The approval of LUTATHERA^® is based on results of a randomized pivotal Phase 3 study, NETTER-1 that compared treatment using LUTATHERA^® plus best standard of care (octreotide LAR 30mg every four weeks) to 60 mg of octreotide LAR alone (also dosed every four weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors, as well as a subset of efficacy and safety data from an international, single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, Netherlands in more than 1,200 patients with somatostatin receptor positive tumors.

Jonathan Strosberg, MD, Associate Professor, Section Head, Neuroendocrine Tumor Program at Moffitt Cancer Center, and NETTER-1 lead investigator, commented "There are very few effective treatment options for patients with inoperable, advanced GEP-NETs who are progressive on somatostatin analogues. As a medical oncologist seeing more than 500 patients with NETs each year, I am grateful to have another tool in my arsenal."

Josh Mailman, President of the Northern California Carcinoid / Neuroendocrine Community, noted, "The approval of LUTATHERA^® marks an exciting day for the NET community in the United States. Due to the rarity of NETs and the challenges that many face in obtaining a diagnosis, many patients are not diagnosed until their disease has become quite advanced and is much more difficult to manage. The approval of every new therapy offers hope to these patients and their families."

The NETTER-1 study met its primary endpoint, showing a 79% reduction in risk of disease progression or death in the LUTATHERA^® arm compared to the 60 mg octreotide LAR arm (hazard ratio 0.21, 95% CI: 0.13-0.32; p<0.0001).³ Median PFS was not reached in the LUTATHERA^® arm compared to 8.5 months for the 60 mg octreotide LAR arm.³ A pre-planned interim overall survival analysis determined that LUTATHERA^® treatment lead to a 48% reduction in the estimated risk of death (hazard ratio 0.52, 95% CI: 0.32-0.84) compared to treatment with 60 mg octreotide LAR.³ The objective response rate, composed of complete and partial responses, was 13% for the LUTATHERA^® arm compared to 4% in the Octreotide LAR 60mg arm (p<0.0148).³

The most common Grade 3-4 adverse reactions occurring with a greater frequency among patients in the NETTER-1 study receiving LUTATHERA^® with octreotide compared to patients receiving high-dose octreotide include: lymphopenia (44%), increased gamma-glutamyl transferase (20%), vomiting (7%), nausea and elevated aspartate aminotransferase (5% each), and increased alanine aminotransferase, hyperglycemia and hypokalemia (4% each).³

About LUTATHERA^® (lutetium Lu 177 dotatate) and How it Works

LUTATHERA^® is a lutetium Lu 177-labeled somatostatin analog peptide. This first-in-class drug belongs to a class of treatments called Peptide Receptor Radionuclide Therapy (PRRT). PRRT is a form of targeted treatment comprised of a targeting molecule which carries a radioactive component. Once administered through infusion drip into the bloodstream, the targeting molecule binds to a specific receptor on tumor cells, and is then internalized into the target cells, where the radioactive component destroys the tumor cells from within. LUTATHERA^® has received orphan drug designation from the FDA and the European Medicines Agency (EMA). LUTATHERA^® has been administered to more than 2,000 patients on a compassionate use and named patient basis for the treatment of NETs and other tumors over-expressing somatostatin receptors in 10 European countries and in the US under an Expanded Access Program (EAP).