ITM Isotopen Technologien München AG, a specialized radiopharmaceutical company, today announced that the European Medicines Agency (EMA) has granted Marketing Authorization for EndolucinBeta® of ITM´s subsidiary ITG Isotope Technologies Garching GmbH. This decision follows a positive recommendation from the European Committee for Medicinal Products for Human Use (CHMP) in May of this year.
EndolucinBeta® respectively no-carrier-added (n.c.a.) Lutetium (177Lu) chloride is used in Targeted Radionuclide Therapy, e.g. in the field of Precision Oncology. It is a radiopharmaceutical precursor, used for radiolabeling of disease-specific carrier molecules, like antibodies or peptides. 177Lu has successfully been used for the treatment of inoperable or metastasized neuroendocrine tumors (NET) by radiolabeling with Somatostatin analogues1 for example with the peptide DOTATOC (Edotreotide).2 Somatostatin receptors are predominantly overexpressed by NETs. The radiopharmaceutical, upon binding to the Somatostatin receptor is in vivo internalized and retained by tumor cells. Upon decay, 177Lu emits cytotoxic medium-energy beta particles with a maximum range of 1.7 mm in soft tissue, which means that healthy tissue in the surroundings of the targeted tumor is minimally affected.
Currently EndolucinBeta® is successfully used in investigational medicinal products for radiolabeling of peptides or antibodies. A recently published retrospective Phase II study with DOTATOC radiolabeled with EndolucinBeta® showed promising efficacy and safety data. These results suggest and demonstrate a significant benefit, a substantially improved progression-free survival (PFS), for which n.c.a. 177Lu-DOTATOC received an Orphan Designation (EMA/OD/196/13)3 as a treatment of gastro-entero-pancreatic neuroendocrine tumors (GEP-NET).4
Steffen Schuster, Chief Executive Officer of the ITM Group, commented: “We are very pleased that EndolucinBeta® now received Marketing Authorization. In the past promising results have already been achieved by combining EndolucinBeta® with disease-specific targeting molecules for Radionuclide Therapy especially with DOTATOC. In the future these encouraging results of n.c.a. 177Lu-DOTATOC need to be confirmed in a multi-center Phase III study.”
EndolucinBeta® is a radiopharmaceutical precursor with a half-life of 6.647 days, usable for radiolabeling of disease-specific carrier molecules. The active substance of EndolucinBeta® is nocarrier- added (n.c.a.) Lutetium (177Lu) chloride. No-carrier-added 177Lu provides the highest specific activity of more than 3,000 GBq/mg at Activity Reference Time (ART), whereas the day of ART can be flexibly selected by the customer. Optimal preconditions for efficient radio labeling of biomolecules over its entire shelf-life of 9 days after production are ensured. Furthermore EndolucinBeta® exhibits an extraordinary level of radionuclidic purity. EndolucinBeta® does not contain metastable 177mLu, thus, there is no need of logistics and storage of contaminated radioactive waste.
About Targeted Radionuclide Therapy
Targeted Radionuclide Therapy is a medical specialty using very small amounts of radioactive compounds, called radiopharmaceuticals, to diagnose and treat various diseases, like cancer. Targeted radiopharmaceuticals contain a targeting molecule (e.g. peptide or antibody) and a medical radioactive isotope. The targeting molecule binds to a tumor specific receptor, according to the lock and key principle. In most cases the targeting molecule can be used for both diagnosis and therapy - only the radioisotope has to be changed. This opens up the way for the application of Theranostics in the field of Precision Oncology.
For diagnostic applications radioisotopes with short half-lives are used. With highly sensitive molecular imaging technologies like PET (Positron Emission Tomography) or SPECT (Single Photon Emission Tomography), pictures of organs and lesions can be created and diseases can therefore be diagnosed in their early stages. Medical radioisotopes with longer half-lives are applied for treatment. To destroying the tumor minimal cytotoxic doses of ionizing radiation have to be submitted to the tumor site before decay. A highly precise localization of the toxicity ensures that healthy tissue in the surroundings of the targeted tumor is minimally affected.
ITM Isotopen Technologien München AG is a privately held group of companies dedicated to the development, production and global supply of innovative diagnostic and therapeutic radionuclides and radiopharmaceuticals. Since its foundation in 2004, ITM and its subsidiaries have established the GMP manufacturing and a robust global supply network of a novel, first-class medical radionuclides and -generator platform for a new generation of targeted cancer diagnostics and therapies. Furthermore, ITM is developing a proprietary portfolio and growing pipeline of targeted treatments in various stages of clinical development addressing a range of cancers such as neuroendocrine cancers or bone metastases. ITM’s main objectives, together with its scientific, medical and industrial collaboration partners worldwide, are to significantly improve outcomes and quality of life for cancer patients while at the same time reducing side-effects and improving health economics through a new generation of Targeted Radionuclide Therapies in Precision Oncology.
For more information about ITM, please visit: www.itm.ag
Important Safety Information for EndolucinBeta® (Lutetium (177Lu) chloride)
Hydrochloric acid solution
EndolucinBeta® is a radiopharmaceutical precursor, and it must not be used directly in patients. It is to be used only for the radiolabeling of carrier molecules that have been specifically developed and authorized for radiolabeling with Lutetium (177Lu) chloride.
Hypersensitivity to the active substance or to any of the excipients.
Established or suspected pregnancy or when pregnancy has not been excluded.
For information on contraindications to particular Lutetium (177Lu)-labeled medicinal products prepared by radio labeling with EndolucinBeta®, refer to the Summary of Product Characteristics /package leaflet of the particular medicinal product to be radiolabeled.
Adverse reactions following the administration of a Lutetium (177Lu)-labeled medicinal product prepared by radio labeling with EndolucinBeta® will be dependent on the specific medicinal product being used. Such information will be supplied in the Summary of Product Characteristics/package leaflet of the medicinal product to be radiolabeled.
Exposure to ionizing radiation is linked with cancer induction and a potential for development of hereditary defects. The radiation dose resulting from therapeutic exposure may result in higher incidence of cancer and mutations. In all cases, it is necessary to ensure that the risks of the radiation are less than from the disease itself.
Special warnings and precautions for use
EndolucinBeta® contains a radioactive substance. Read the package leaflet before use.
For administration after in vitro radiolabeling. Store in the original package in order to avoid unnecessary radiation exposure. Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials. Any unused medicinal product or waste material must be disposed of in accordance with local requirements. Keep out of the sight and reach of children. Medicinal product subject to restricted medical prescription.
Marketing Authorization Holder
ITG Isotope Technologies Garching GmbH
85748 Garching, Germany
For full prescribing information please see:
1. Janson ET, Sorbye H, Welin S, Federspiel B, Gronbaek H, Hellman P, Mathisen O, Mortensen J, Sundin A, Thiis-Evensen E, Välimäki MJ, Oberg K, Knigge U.
Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours. Acta Oncol 2010;49:740-56.
Joseph S, Wang YZ, Boudreaux JP, Anthony LB, Campeau R, Raines D, O'Dorisio T, Go VL, Vinik AI, Cundiff J, Woltering EA. Neuroendocrine tumors: current recommendations for diagnosis and surgical management. Endocrinol Metab Clin North Am 2011;40:205-31.
Parus JL, Mikolajczak R. Beta-emitting radionuclides for peptide receptor radionuclide therapy. Curr Top Med Chem 2012;12:2686-93.
Öberg K, Knigge U, Kwekkeboom D, Perren A; ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl 7):vii124-30.
2. van Essen M, Krenning EP, De Jong M, Valkema R, Kwekkeboom DJ. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol 2007a;46:723-34.
Kwekkeboom DJ, Teunissen JJ, Kam BL, Valkema R, de Herder WW, Krenning EP. Treatment of patients who have endocrine gastroenteropancreatic tumors with radiolabeled somatostatin analogues. Hematol Oncol Clin North Am 2007;21:561-73.
Kwekkeboom DJ, de Herder WW, van Eijck CH, Kam BL, van Essen M, Teunissen JJ, Krenning EP. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2010;40:78-88.
Teunissen JJ, Kwekkeboom DJ, Valkema R, Krenning EP. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr Relat Cancer 2011;18(Suppl 1):S27-51.
Wang L, Tang K, Zhang Q, Li H, Wen Z, Zhang H, Zhang H. Somatostatin receptor-based molecular imaging and therapy for neuroendocrine tumors.
Biomed Res Int 2013;2013:102819.
van Vliet EI, Teunissen JJ, Kam BL, de Jong M, Krenning EP, Kwekkeboom DJ. Treatment of gastroenteropancreatic neuroendocrine tumors with peptide receptor radionuclide therapy. Neuroendocrinology 2013a;97:74-85.
3. European Commission, Public Health, Pharmaceuticals – Community Register, Community Register of Orphan Medicinal Products. Available at: http://ec.europa.eu/health/documents/community-register/html/o1269.htm
4. Baum RP, Kluge A, Kulkarni H, Schorr-Neufing U, Niepsch K, Bitterlich N, and Van Echteld C, (2016). [177Lu-DOTA]0-D-Phe1-Tyr3-octreotide (177Lu-DOTATOC) for Peptide Receptor Radiotherapy in patients with advanced Neuroendocrine Tumors: A retrospective Phase II study of efficacy and safety. Theranostics). 6(4):501-510.
Schuchardt C, Kulkarni HR, Prasad V, Zachert C, Müller D, and Baum RP (2013). The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC. Recent results in cancer research. 194: 519 -53.
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ITM Isotopen Technologien München AG
Chairman of the Supervisory Board - Udo J. Vetter, Executive Board - Steffen Schuster (Chairman), Thomas Dürre
Registered Office of the Company - Lichtenbergstr. 1, 85748 Garching – Commercial Register Munich - HRB 154944