DOCSLIB.ORG

PEPTIDES in CANCER RESEARCH Cancer Research

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PEPTIDES in CANCER RESEARCH Cancer Research PEPTIDES IN CANCER RESEARCH Cancer Research PEPTIDE-BASED CANCER THERAPEUTICS This brochure discusses the potential use of peptides as anti- cancer drugs highlighting current scenario and future prospects. Some peptides are also used as diagnostic tools for cancer detection. G-protein-coupled receptors are most important targets in drug development. Many of them are overexpressed in tumor cells. Amongst them, the GnRH receptor is the target of a consider- able number of GnRH agonists and antagonists used in cancer management. GnRH (gonadotropin-releasing hormone) or LHRH (luteinizing hormone-releasing hormone) is a decapeptide pro- duced in in the hypothalamus and released in a pulsatile fashion into the pituitary portal circulation. Prolonged non-pulsatile administration of LHRH leads to down-regulation of LH and FSH secretion, followed by a suppression of gonadal steroid synthesis. For this reason, longer-acting GnRH agonists as well as antago- nists are used for the treatment of hormone-dependent breast and prostate cancers. Most neuroendocrine tumors show a marked overexpression of somatostatin receptors, especially of sst2, which instigated the development of somatostatin agonists as octreotide. These compounds also play an important role in diagnosis. Bombesin/gastrin-releasing peptide receptors can be overex- pressed in malignant cells. Antagonists of these peptides inhibit tumor growth. Active immunization by peptide vaccines is another promising strategy to fight cancer. 2 Introduction penetrate tumor tissue. Their proteolytic Cancer is characterized by uncontrolled degradation can be conveniently prevented division of cells and the ability of these by chemical modifications such as incor- cells to invade other tissues leading to the poration of D-amino acids or cyclization. formation of tumor mass, to vasculariza- Properties of bicyclic peptides are even tion and, finally, to metastasis (spread of better and comparable to those of antibody cancer to other parts of the body). Though drugs. angiogenesis (growth of new blood vessels The peptide drugs currently available on the from existing vessels) is a normal and vital market can be classified as analogs and process during growth and development, it antagonists of peptide hormones or tumor is also a fundamental step in the transition targeting agents carrying radionuclides. of tumors from a dormant state to a malig- nant one. So, angiogenesis inhibitors have LHRH (GnRH) Agonists and Antagonists been used to suppress tumor cell growth. The first example for the introduction of Chemotherapy is one of the classical ap- peptide drugs into cancer therapy is the proaches to treat cancer, a cytotoxic agent use of LHRH (luteinizing hormone-releasing is delivered to the cancer cells. The main hormone) analogs. Schally et al. developed problem with conventional chemotherapy the first GnRH agonists which later were is its inability to administer the correct applied in the treatment of prostate and amount of drug directly to cancer cells with- breast cancer. Since then, peptides such as out affecting normal cells. Drug resistance, altered biodistribution, biotransformation and premature clearance are also common problems. Targeted chemotherapy and drug MODIFICATION AT delivery techniques are emerging as a pow- erful method to circumvent such problems. This will allow the selective and effec- POSITION 6 WITH tive localization of drugs at pre-defined targets (e.g. overexpressed receptors) while A D-AMINO ACID restricting its access to normal cell thus maximizing therapeutic index and reduc- ing toxicity. The discovery of further recep- YIELDS POTENT tors abnormally expressed in cancer cells and tumor-related peptides and proteins is expected to lead to a ‘new wave’ of more LONG-ACTING effective and selective anti-cancer drugs in the future. LHRH AGONISTS The “biologics” approach to cancer therapy includes application of proteins, monoclo- nal antibodies and peptides. Monoclonal buserelin, leuprolide, goserelin, histrelin, antibodies (mAb) and large protein ligands and triptorelin have been developed and have two major limitations compared to approved in cancer therapy. Depot formu- peptides: poor delivery to tumors due to lations of these peptides allow for a more their large size and a dose-limiting toxicity efficacious and convenient treatment of pa- in liver and bone marrow due to nonspecific tients with prostate cancer. Administration uptake into the reticuloendothelial system. of these peptides effects a down-regulation The use of such macromolecules has there- of GnRH receptors in the pituitary, leading fore been restricted to vascular targets to an inhibition of follicle-stimulating hor- present on the luminal side of the tumor mone (FSH) and LH release, and a concomi- vessel endothelium and to hematological tant decrease in testosterone production. malignancies. The introduction of LHRH antagonists as Peptides possess many advantages such as cetrorelix resulted in therapeutic improve- small size, ease of synthesis and modi- ment over agonists as they cause an imme- fication, they are biocompatible and can diate and dose-related inhibition of LH and 3 Cancer Research PEPTIDE SEQUENCE INDICATION GnRH GONADORELIN Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH₂ none in cancer therapy GnRH Agonists BUSERELIN Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt Prostate cancer GOSERELIN Pyr-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-Azagly-NH₂ Prostate and breast cancer HISTRELIN Pyr-His-Trp-Ser-Tyr-D-His(Bzl)-Leu-Arg-Pro-NHEt Prostate and breast cancer LEUPROLIDE Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt Prostate and breast cancer TRIPTORELIN Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH₂ Prostate and breast cancer GnRH Antagonists ABARELIX Ac-D-2-Nal-D-4-Cpa-D-3-Pal-Ser-N-Me-Tyr-D-Asn- Prostate cancer Leu-Lys(isopropyl)-Pro-D-Ala-NH₂ CETRORELIX Ac-D-2-Nal-4-chloro-D-Phe-β-(3-pyridyl)-D-Ala-Ser- Prostate and breast cancer Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH₂ DEGARELX Ac-D-2-Nal-D-4-Cpa-D-3-Pal-Ser-4-amino-Phe(L-4,5- Prostate cancer dihydroorotyl)-4-ureido-D-Phe-Leu-Lys(isopropyl)-Pro- D-Ala-NH₂ OZARELIX Ac-D-2-Nal-D-4-Cpa-D-3-Pal-Ser-N-Me-Tyr-D-Hci- Prostate cancer Nle-Arg-Pro-D-Ala-NH₂ TEVERELIX Ac-D-2-Nal-D-4-Cpa-D-3-Pal-Ser-Tyr-D-Hci-Leu- Prostate cancer Lys(isopropyl)-Pro-D-Ala-NH₂ Table1. LHRH agonists and new generation antagonists available in the market. FSH by competitive blockade of the LHRH Most neuroendocrine tumors (NETs) feature receptors. To date, many potent GnRH an- a strong overexpression of somatostatin tagonists are available for therapeutic use receptors, mainly of subtype 2 (sst2). Cur- in patients suffering from prostate cancer. A rently, five somatostatin receptor subtypes list of such agonists and antagonists avail- (sst) are known (sst1-5). The density of able in the market can be found in Table 1 these receptors on tumor tissue is vastly higher than on healthy tissue. Therefore, Somatostatin Analogs in Cancer Therapy sst are attractive targets for delivery of Apart from the use of peptidic LHRH ago- radionuclides employing appropriately nists and antagonists for treating cancer, modified somatostatin analogs. Introduced somatostatin analogs are the only approved in the late 1980s by Sandoz, [111In-DTPA]- cancer therapeutic peptides in the market. octreotide (pentetreotide, Octreoscan®), Potent agonists of somatostatin (SRIF) in- rapidly became the gold standard for cluding octreotide (sandostatin) have been diagnosis of sst-positive NETs. Numer- developed for the treatment of acromegaly, ous peptide-based tumor-imaging agents gigantism and thyrotropinoma associated targeting sst have been developed over the with carcinoid syndrome, and diarrhea in past decades. Octreoscan® and NeoTect® patients with vasoactive intestinal peptide- (technetium-99m-labeled depreotide, secreting tumors (VIPomas). Lanreotide, cyclo(MePhe-Tyr-D-Trp-Lys-Val-Hcy(CH2CO- another long-acting analog of somatostatin, β-Dap-Lys-Cys-Lys-NH2)) are the only is used in the management of acromegaly radiopeptide tracers on the market ap- and symptoms caused by neuroendocrine proved by the FDA. An octreotide scan or tumors. octreoscan is a scintigraphic method used 4 THE FIVE KNOWN SOMATOSTATIN RECEPTORS ARE ATTRACTIVE TARGETS FOR TUMOR DIAGNOSIS AND THERAPY to find carcinoids and other types of tumors cancerous cells relies on vaccines consist- and to localize sarcoidosis. DTPA-Octreo- ing of peptides derived from the amino acid tide, after radiolabeling with indium-111, sequence of candidate tumor-associated or is injected into a vein and travels through specific antigens. Tumor cells express anti- the bloodstream. The radioactive octreotide gens known as tumor-associated antigens attaches to tumor cells that have receptors (TAAs) that can be recognized by the T-cells for somatostatin. A radiation-measuring of the host’s immune system. A consider- device detects the radioactive octreotide, able number of TAAs could be identified and and generates images showing the precise characterized. TAAs can be injected into location of the tumor in the body. cancer patients in an attempt to induce a The principle also works in cancer therapy. systemic immune response that may result Peptide receptor radionuclide therapy in the destruction of the cancer cells. Any (PRRT) combines appropriately modified oc- protein/peptide produced in a tumor cell treotide with a radionuclide, which will bind that has mal structure due to mutation to carcinoid tumor cells with overexpressed can act as a tumor antigen. Such abnormal somatostatin receptors. Once bound, the proteins are produced due to mutations targeted radiation will kill the malignant in the corresponding gene. Hence, clinical cells the peptide is bound to. The complex between radionuclide and peptide has to be stable, especially if the radiopeptide is used in therapy. Cyclic chelators as DOTA bind (radio)nuclides as 68Ga, 90Y, or 177Lu more tightly, so (Tyr3)-DOTA- octreotide (DOTATOC, edotreotide) can be used in diagnosis and therapy of NETs. This also holds true for the C-terminal acid, DOTA-octreotate (DOTATATE).
Load more

Recommended publications
  • Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future
    International Journal of Molecular Sciences Review Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future Anna Kathrin Stueven 1, Antonin Kayser 1, Christoph Wetz 2, Holger Amthauer 2, Alexander Wree 1, Frank Tacke 1, Bertram Wiedenmann 1, Christoph Roderburg 1,* and Henning Jann 1 1 Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Hepatology and Gastroenterology, Universitätsmedizin Berlin, 10117 Berlin, Germany; [email protected] (A.K.S.); [email protected] (A.K.); [email protected] (A.W.); [email protected] (F.T.); [email protected] (B.W.); [email protected] (H.J.) 2 Charité, Campus Virchow Klinikum and Charité, Campus Mitte, Department of Nuclear Medicine, Universitätsmedizin Berlin, 10117 Berlin, Germany; [email protected] (C.W.); [email protected] (H.A.) * Correspondence: [email protected]; Tel.: +49-30-450-553022 Received: 3 May 2019; Accepted: 19 June 2019; Published: 22 June 2019 Abstract: In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,682,960 B2 Labrie Et Al
    USOO968296OB2 (12) United States Patent (10) Patent No.: US 9,682,960 B2 Labrie et al. (45) Date of Patent: Jun. 20, 2017 (54) NON-STEROIDAL ANTANDROGENS AND (56) References Cited SELECTIVE ANDROGEN RECEPTOR MODULATORS WITH APYRIDYL MOETY U.S. PATENT DOCUMENTS 3,742.951 7, 1973 Zaffaroni (71) Applicants: Fernand Labrie, Quebec (CA); 3,797.494 3, 1974 Zaffaroni Shankar Mohan Singh, Quebec (CA); 4,568,343 2, 1986 Leeper et al. Richard Labrecque, St-Nicolas (CA); 5,064,654 11, 1991 Berner et al. 5,071,644 12, 1991 Viegas et al. Liviu Constantin Ciobanu, Quebec 5,071,657 12, 1991 Oloff et al. (CA) 5,411,981 5, 1995 Gaillard-Kelly et al. 5,556,983 9, 1996 Claussner et al. (72) Inventors: Fernand Labrie, Quebec (CA); 5,750,553 5, 1998 Claussner et al. 6,071,957 6/2000 Miller et al. Shankar Mohan Singh, Quebec (CA); 7/2000 Claussner et al. Richard Labrecque, St-Nicolas (CA); 6,087,509 Liviu Constantin Ciobanu, Quebec (Continued) (CA) FOREIGN PATENT DOCUMENTS (73) Assignee: ENDORECHERCHE, INC. (CA) CA 2 677 295 9, 2008 CA 2 773 591 3, 2011 EP 0 002892 A1 7/1979 (*) Notice: Subject to any disclaimer, the term of this EP O 100 172 A1 2, 1984 patent is extended or adjusted under 35 EP O 279 982 A1 8, 1988 U.S.C. 154(b) by 0 days. EP O 494 819 A1 7, 1992 EP O 578516 A1 1, 1994 Appl. No.: 14/567,970 EP O 580 459 A1 1, 1994 (21) FR 2 671 348 A1 7, 1992 Filed: Dec.
    [Show full text]
  • Multi-Discipline Review(S)
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 210828Orig1s000 MULTI-DISCIPLINE REVIEW Summary Review Clinical Review Non-Clinical Review Statistical Review Clinical Pharmacology Review NDA/BLA Multi-Disciplinary Review and Evaluation (NDA 210828) 505(b)(2) (Ga-68-DOTATOC) NDA/BLA Multi-Disciplinary Review and Evaluation Application Type NME & 505 (b)(2) Application Number(s) NDA 210828 Priority or Standard Standard Submit Date(s) May 23, 2018 Received Date(s) May 23, 2018 PDUFA Goal Date August 23, 2019 Division/Office Office of Drug Evaluation IV/Division of Medical Imaging Products (DMIP/ODEIV) Review Completion Date TBD Established/Proper Name Ga-68-DOTATOC injection (Proposed) Trade Name Not applicable Pharmacologic Class Radioactive diagnostic agent Code name IC2000 Applicant University of Iowa Health Care/P.E.T. Imaging Center Dosage Form Injection: Clear, colorless solution containing 18.5 to 148 MBq/mL (0.5 to 4 mCi/mL) of Ga-68-DOTATOC injection at end of synthesis (EOS) (approximately 14 mL volume) in a 30 mL multiple-dose vial. Applicant proposed Dosing For adults: 148 MBq (4 mCi); for pediatric patients: 1.59 Regimen MBq/kg (0.043 mCi/kg) with a range of 11.1 MBq (0.3 mCi) to 111 MBq (3 mCi) Applicant Proposed For localization of somatostatin receptor positive (b) (4) Indication(s)/Population(s) neuroendocrine tumors (NETs) in (b) (4) adult and pediatric patients. Applicant Proposed Indicated for use with positron emission tomography (PET) for SNOMED CT Indication localization of somatostatin receptor positive neuroendocrine (b) (4) Disease Term for Each tumors (NETs) in adult and pediatric (b) (4) Proposed Indication patients.
    [Show full text]
  • WO 2018/144603 Al 09 August 2018 (09.08.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/144603 Al 09 August 2018 (09.08.2018) W !P O PCT (51) International Patent Classification: A61K 38/09 (2006 .01) A61P 35/00 (2006.0 1) (21) International Application Number: PCT/US20 18/0 16241 (22) International Filing Date: 31 January 2018 (3 1.01.2018) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/452,788 31 January 2017 (3 1.01.2017) US (71) Applicant: VERU INC. [US/US]; 4400 Biscayne Blvd., #888, Miami, Florida 33 137 (US). (72) Inventors: RAVI, Kacker; 39 Paul Revere Road, Lexing ton, Massachusetts 02421 (US). MITCHELL S., Stein- er; 2600 Forest Hill Road, Germantown, Tennessee 38139 (US). (74) Agent: COHEN, Mark S. et al; PEARL COHEN ZEDEK LATZER BARATZ LLP, 1500 Broadway, 12th Floor, New York, New York 10036 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Spectrum Pharmaceuticals Initiates US Clinical
    Spectrum Pharmaceuticals Initiates U.S. Clinical Trial of Ozarelix (SPI-153) in Patients with Hormone-Dependent Prostate Cancer - Ozalerix is currently in two multicenter trials underway in Europe - one in benign prostate hypertrophy (BPH) and another in hormone dependent prostate cancer - Spectrum now has five drugs in multiple clinical trials, including one in phase III IRVINE, Calif., July 25 /PRNewswire-FirstCall/ -- Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI) today announced the launch of a phase I/II trial in the United States to explore the safe and efficacious dose range of ozarelix (formerly SPI-153) as a treatment for patients with hormone- dependent prostate cancer. "We are pleased to advance the development of ozarelix in the United States with the start of this clinical study," stated Rajesh Shrotriya, M.D., Chairman of the Board, Chief Executive Officer and President of Spectrum Pharmaceuticals, Inc. "This study will provide us additional valuable information regarding the optimum dose range for testosterone suppression, an important outcome measure in the management of hormone-dependent prostate cancer." About Prostate Cancer Prostate cancer is the second leading cause of cancer deaths in men and occurs when a malignant tumor forms in the tissue of the prostate. According to figures released by the American Cancer Society, approximately 232,090 new cases and 30,350 deaths will occur in the U.S. during 2005. The initial treatment of prostate cancer included surgery along with radiation therapy and hormonal therapy. About Ozarelix Ozarelix is a fourth generation LHRH (Luteinizing Hormone Releasing Hormone), also known as GnRH (Gonadotropin Releasing Hormone), antagonist. LHRH antagonists have the potential to treat hormone-dependent cancers as well as benign proliferative disorders such as benign prostatic hypertrophy and endometriosis.
    [Show full text]
  • View Annual Report
    Spectrum Pharmaceuticals, Inc. CANCER TAKES THE LIVES OF OVER SEVEN MILLION PEOPLE WORLDWIDE EACH YEAR www.spectrumpharm.com 157 Technology Drive, Irvine, California 92618 Telephone 949.788.6700 2005 Annual Report spECTRUM PHARMACEUTicALS, INC. SPECTRUM O U R T E A M PHARMACEUTicALS BOARD OF DIRECTORS MANAGEMENT TEAM OUTSIDE COUNSEL Rajesh C. Shrotriya, M.D. Rajesh C. Shrotriya, M.D. Latham & Watkins LLP Chairman of the Board, Chief Executive Officer Chairman, Chief Executive Officer & President Costa Mesa, California is COMMITTED TO & President, Spectrum Pharmaceuticals, Inc. Luigi Lenaz, M.D. I NDEPENDENT A UDITORS Richard D. Fulmer, M.B.A. Chief Scientific Officer Kelly & Company Former Vice President, Licensing and Development, Costa Mesa, California IMPROVING THE and Vice President of Marketing, Pfizer Inc. Shyam K. Kumaria, CPA, MBA Vice President, Finance T R A N S F E R A GENT Stuart M. Krassner, Sc.D., Ph.D. U.S. Stock Transfer Corporation LIVES OF PEOPLE Professor Emeritus of Developmental and Russell L. Skibsted Glendale, California Cell Biology at the School of Biological Sciences Senior Vice President, Chief Business Officer University of California at Irvine SEC F O R M 1 0 - K Ashok Y. Gore, Ph.D. Please see the enclosed Annual Report on Form WHO ARE FIGHTING Anthony E. Maida, III, M.A., M.B.A. Senior Vice President, Pharmaceutical 10-K filed with the Securities and Exchange Chairman, BioConsul Drug Development Operations & Regulatory Compliance Commission for a more detailed description Corporation and DendriTherapeutics, Inc. of the Company’s business, financial and other Consultant to various Venture Capital, William N.
    [Show full text]
  • 2016 Medicines in Development for Rare Diseases a LIST of ORPHAN DRUGS in the PIPELINE
    2016 Medicines in Development for Rare Diseases A LIST OF ORPHAN DRUGS IN THE PIPELINE Autoimmune Diseases Product Name Sponsor Official FDA Designation* Development Status Actemra® Genentech treatment of systemic sclerosis Phase III tocilizumab South San Francisco, CA www.gene.com Adempas® Bayer HealthCare Pharmaceuticals treatment of systemic sclerosis Phase II riociguat Whippany, NJ www.pharma.bayer.com ARA 290 Araim Pharmaceuticals treatment of neuropathic pain in patients Phase II Tarrytown, NY with sarcoidosis www.ariampharma.com ARG201 arGentis Pharmaceuticals treatment of diffuse systemic sclerosis Phase II (type 1 native bovine skin Collierville, TN www.argentisrx.com collagen) BYM338 Novartis Pharmaceuticals treatment of inclusion body myositis Phase III (bimagrumab) East Hanover, NJ www.novartis.com CCX168 ChemoCentryx treatment of anti-neutrophil cytoplasmic Phase II (5a receptor antagonist) Mountain View, CA auto-antibodies associated vasculitides www.chemocentryx.com (granulomatosis with polyangitis or Wegener's granulomatosis), microscopic polyangitis, and Churg-Strauss syndrome * This designation is issued by the FDA's Office of Orphan Products Development while the drug is still in development. The designation makes the sponsor of the drug eligible for entitlements under the Orphan Drug Act of 1983. The entitlements include seven years of marketing exclusivity following FDA approval of the drug for the designated use. Medicines in Development: Rare Diseases | 2016 1 Autoimmune Diseases Product Name Sponsor Official FDA
    [Show full text]
  • Spectrum Announces Completion of Patient Enrollment in Ozarelix Phase II Trial in Patients with Benign Prostatic Hypertrophy
    Spectrum Announces Completion of Patient Enrollment in Ozarelix Phase II Trial in Patients With Benign Prostatic Hypertrophy * Enrollment was completed ahead of schedule by more than four months * This is a multicenter, placebo controlled, randomized study in 144 patients with BPH IRVINE, Calif., Nov 21, 2005 /PRNewswire-FirstCall via COMTEX News Network/ -- Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI) today announced that the Company has achieved complete enrollment for a phase II trial of ozarelix in Benign Prostatic Hypertrophy (BPH), more that four months ahead of schedule. The multi-center clinical trial is designed to evaluate both objective parameters, such as improvement in urine flow and shrinkage of the prostate volume, as well as various symptoms of BPH over a period of several months. The trial is conducted in Europe with the collaboration of AEterna Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ), "We are pleased to report that this multicenter, placebo controlled, randomized, phase II trial that was started only in April this year, has already achieved its goal of enrolling 144 patients, ahead of our projections by more than four months," stated Rajesh C. Shrotriya, M.D., Chairman, Chief Executive Officer and President. "Non-cancerous, enlargement of the prostate (BPH) adversely affects the quality of life, leading to increased frequency of urination and difficulty in passing urine. Because ozarelix is expected to have dual effects: (1), by directly shrinking the prostate and (2), through controlled reduction in the amount of testosterone (testosterone fuels the prostate gland), our expectation is that a single injection of ozarelix, repeated every few months, may be able to reduce the size of the prostate as well as accompanying symptoms." About Benign Prostatic Hypertrophy Benign prostatic hypertrophy is a non-cancerous enlargement of the prostate frequently occurring in men over the age of 50.
    [Show full text]
  • First Patient in Phase III Clinical Trial COMPETE with N.C.A.177Lu-Edotreotide (Solucin®) in Cancer Patients with GEP-NET
    Garching, Germany, April 18, 2017 First Patient in Phase III Clinical Trial COMPETE with n.c.a.177Lu-Edotreotide (Solucin®) in Cancer Patients with GEP-NET Solucin® (n.c.a. 177Lu-Edotreotide) to be shown as a highly precise and effective Targeted Radionuclide Therapy Agent Promising data of Solucin® expected to be confirmed in phase III clinical trial COMPETE Solucin® to demonstrate prolonged PFS compared to mTOR inhibitor Everolimus ITM Isotopen Technologien München AG (ITM), a specialized radiopharmaceutical company, today announced the enrollment of the first patient recruited in the COMPETE study, an international pivotal multi-center phase III clinical trial evaluating the efficacy and safety of n.c.a.177Lu-Edotreotide (Solucin®) compared to Everolimus in patients with inoperable, progressive, somatostatin-receptor positive neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET). The primary endpoint is progression-free survival (PFS). With Solucin® a retrospective phase II efficacy and safety study of Targeted Radionuclide Therapy in patients with advanced neuroendocrine tumors (NET) with encouraging results has been performed. The results suggest and demonstrate a significant benefit, a substantially improved progression-free survival (PFS).1 Therefore Solucin® received an Orphan Designation (EMA/OD/196/13). Due to these favorable data and the long-term experience with n.c.a. 177Lu-Edotreotide under compassionate use, ITM is positive to verify the results in the clinical phase III trial, known as COMPETE. The study will be conducted predominantly in Europe, North America, South Africa and Australia. The first patient has been enrolled and will be treated in Australia. Solucin® is injected into the patient´s body where it specifically accumulates at the tumor.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2010/0190692 A1 VAN GROENINGHEN (43) Pub
    US 20100190692A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0190692 A1 VAN GROENINGHEN (43) Pub. Date: Jul. 29, 2010 (54) METHODS FOR REDUCING Publication Classification GNRH-POSITIVE TUMIORCELL (51) Int. Cl. PROLIFERATION A638/09 (2006.01) (76) Inventor: JOHANNES C. VAN A638/22 (2006.01) GROENINGHEN, Dortmund (DE) A 6LX 3/59 (2006.01) s A63L/704 (2006.01) Correspondence Address: Age, 30.8; } GRUND INTELLECTUAL PROPERTY GROUP NKOLAISTRASSE 15 (52) U.S. Cl. .............. 514/8: 514/15; 514/259.5; 514/34; (57) ABSTRACT (21) Appl. No.: 12/701,284 A method for recognizing and evaluating the presence and (22) Filed: Feb. 5, 2010 function of GnRH receptors on tumor cells originating in the brain and/or nervous system and/or the meninges and/or reac Related U.S. Application Data tive neuroglia cells and/or primitive neuroectodermal tumor cells and/or on Kaposi sarcoma is provided. Furthermore a (63) Continuation-in-part of application No. 10/327,621, method for reducing degenerate GnRH-positive tumor cells filed on Dec. 20, 2002, now Pat. No. 7,695,722, which and/or for decreasing cellular replication of the above GnRH is a continuation-in-part of application No. 09/446, positive tumor cells comprising administering to a cell or to a 996, filed on Dec. 30, 1999, now abandoned, filed as Subject a replication decreasing amount of a GnRH agonist application No. PCT/DE98/01902 on Jul. 3, 1998. and/or GnRH antagonist and/or an erythropoietin agonist, and/or a thrombopoietin agonist, and/or a endothelin antago (30) Foreign Application Priority Data nist and/or a gonadotropin inhibiting hormone agonist is also provided.
    [Show full text]
  • Ongoing and Future Clinical Investigation in GEP Nens
    ESMO PRECEPTORSHIP PROGRAMME Multidisciplinary management, standards of care and future perspectives Lugano, Switzerland 13-14 April 2018 CHAIR: Nicola Fazio, Italy SPEAKERS: Pier Luigi Filosso, Italy George Pentheroudakis, Greece Andrea Frilling, United Kingdom Rocio Garcia-Carbonero, Spain Massimo Milione, Italy Marianne Pavel, Germany Aviral Singh, Germany Anders Sundin, Sweden Christos Toumpanakis, United Kingdom LEARNING OBJECTIVES Ongoing• Toand learn about future best clinical practice clinical in the multid isciplinary management of gastroenteropancreatic (GEP) and thoracic neuroendocrine neoplasms (NEN) patients Oncology investigation in GEP NENs of • To learn about the biological and clinical principles of diagnostic and therapeutic strategy Institute • To understand the importance of terminology, pathological and clinical classification, morphological and functional characterization of disease European Nicola Fazio, M.D., Ph. D. • To learn how to manage the integration of several different therapies in patients with advanced disease • To learn how to apply into clinical practice information coming from medical literature, guidelines and recommendations Division of Gastrointestinal Medical Oncology and ACCREDITATION Neuroendocrine Tumors EuropeanThe programme Institute of this event of has Oncology been accredited with 10 ESMO-MORA category 1 points. RecertificationMilan, is necessary Italy for medical oncologists to remain professionally certified by ESMO. Recertification guarantees that a certified medical oncologist has continued
    [Show full text]