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|Advanced Accelerator Applications Receives US FDA Approval for LUTATHERA® for Treatment of Gastroenteropancreatic Neuroendocrine Tumors|
First-in-class Therapy Demonstrated 79% Improvement in Progression Free Survival in NETTER-1 Phase 3 Study in Midgut NET Patients
LUTATHERA® marks first FDA Approval for a Peptide Receptor Radionuclide Therapy (PRRT)
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
Jonathan Strosberg, MD, Associate Professor, Section Head, Neuroendocrine Tumor Program at
Josh Mailman, President of the Northern California Carcinoid /
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
* USAN: lutetium Lu 177 dotatate/INN: lutetium (177Lu) oxodotreotide
1 Dasari A, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017; 3(10):1335-1342.
2 Yao JC, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–3072.
3 LUTATHERA® [prescribing information]. Millburn, NJ:
LUTATHERA® (lutetium Lu 177 dotatate) Important Safety Information3
LUTATHERA® is indicated for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults.
2. WARNINGS AND PRECAUTIONS
3. ADVERSE REACTIONS
The most common Grade 3-4 adverse reactions observed in LUTATHERA® clinical trials were lymphopenia (44%), increased GGT (20%), vomiting (7%), nausea (5%), elevated AST (5%), increased ALT (4%), hyperglycemia (4%), and hypokalemia (4%).
The following serious adverse reactions have been observed with a median follow-up time of more than 4 years after treatment with LUTATHERA®: myelodysplastic syndrome (2%), acute leukemia (1%), renal failure (2%), hypotension (1%), cardiac failure (2%), myocardial infarction (1%), and neuroendocrine hormonal crisis (1%). Patients should be counseled and monitored in accordance with the LUTATHERA® Prescribing Information.
4. DRUG INTERACTIONS
Somatostatin and its analogs competitively bind to somatostatin receptors and may interfere with the efficacy of LUTATHERA®. Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each LUTATHERA® dose. Administer short- and long-acting octreotide during LUTATHERA® treatment as recommended.
Please see full Prescribing Information at: http://www.adacap.com/wp-content/uploads/2018/01/Lutathera_lutetium_Lu_-177_dotatate_PI_2018_01.pdf
Advanced Accelerator Applications (NASDAQ:AAAP), a Novartis company, is an innovative radiopharmaceutical company developing, producing and commercializing molecular nuclear medicine theragnostics. AAA’s theragnostic platform is based on radiolabeling a targeting molecule with either gallium Ga 68 for diagnostic use, or lutetium Lu 177 for therapy. AAA’s first theragnostic pairing for neuroendocrine tumors includes diagnostic drugs NETSPOT® in the US and SomaKit TOC™ in Europe; and therapeutic LUTATHERA® (USAN: lutetium Lu 177 dotatate/INN: lutetium (177Lu) oxodotreotide). Additional theragnostics in development target gastrointestinal stromal tumors (GIST), and prostate and breast cancer. AAA is also an established leader in molecular nuclear diagnostic radiopharmaceuticals for PET and SPECT, mainly used in clinical oncology, cardiology and neurology. Headquartered in Saint-Genis-Pouilly, France, AAA currently has 20 production and R&D facilities, and more than 600 employees in 13 countries (France, Italy, the UK, Germany, Switzerland, Spain, Poland, Portugal, The Netherlands, Belgium, Israel, the US and Canada). AAA reported sales of €109.3 million in 2016 (+23% vs. 2015) and €106.4 million for the first 9 months of 2017 (+31% vs. first 9 months of 2016). AAA is listed on the Nasdaq Global Select Market under the ticker “AAAP”. For more information, please visit: www.adacap.com.
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