抗細菌感染新藥 太捷信® （奈諾沙星，Nemonoxacin）
開發階段
已完成口服劑型社區型肺炎（community-acquired bacterial pneumonia，簡稱CABP或CAP）及糖尿病足感染（diabetic foot infection，簡稱DFI）美國IND二期臨床試驗。
已完成口服劑型社區型肺炎（CAP）台灣及中國之三期臨床試驗，口服膠囊已在中國、台灣上市銷售。
奈諾沙星注射劑型已申請中國新藥查驗登記NDA，台灣三期臨床解盲成功正準備申請NDA。
全球已授權高達32個國家，將陸續上市銷售。
俄羅斯土耳其區域授權夥伴R-Pharm已完成三期臨床試驗解盲成功，目前正著手進行俄羅斯及獨立國協地區的新藥查驗登記、藥證申請及上市核准。
拉美市場授權夥伴Productos científicos正與墨國FDA洽談臨床資料銜接及後續上市申請。
研發成果
1.獲得共十一種不同的專利保護，目前擁有159件專利數目，專利行使範圍包括美國、歐盟、加拿大、中國大陸、韓國、澳洲、台灣等地，專利最長可以保護到西元2030年
2.獲科專補助台幣9,832萬元進行二期臨床試驗
3.獲科專補助台幣880萬元進行三期臨床試驗
4.榮獲2010年經濟部業界開發產業技術計畫-卓越研發成果獎
5.在2012年將中國地區製造及銷售權利授權予浙江醫藥股份有限公司，收到簽約金800萬美元，未來可依研發進度，向浙江醫藥收取里程碑款，以及依奈諾沙星在中國區之銷售淨額收取權利金
6.奈諾沙星獲得國家新創獎及台北生技獎技術移轉獎金獎
7.在2014年將俄羅斯、獨立國協以及土耳其等市場授權予俄羅斯藥廠R-Pharm
8.在2016年將拉丁美洲17國市場授權予墨西哥醫藥集團Productos Científicos
業務發展
1.已取得台灣衛福部核發之藥品許可證，口服膠囊已取得台灣健保核價 每顆180元，行銷已委由在抗生素領域有超過三十年經驗的文德藥業負責。
2.在奈諾沙星上市後，搭配合作夥伴中國浙江醫藥經驗豐富之行銷團隊，及其抗細菌感染藥物之銷售渠道，共同執行奈諾沙星在中國之行銷策略，加速銷售高原期的來臨。
3.奈諾沙星口服劑型在2013年12月中，獲美國FDA認定屬於可對抗具抗藥性細菌等病原體之「抗感染藥品」（Qualified Infectious Disease Product，簡稱QIDP）資格 ，並獲美國FDA給予「快速通道」（Fast Track）待遇。獲得QIDP之藥品可獲得額外5年獨賣許可，若加上NCE（創新化合物）之5年專賣期，即長達10年。另外FDA授予的「快速通道」待遇，將讓奈諾沙星擁有優先審查之資格，有利於加速藥物上市時間。太景與太景之授權伙伴，將可因此受惠。
Presentations
2017 ECCMID
In vitro Activity of Nemonoxacin Against Streptococcus pnuemoniae and Haemophilus influenzae– Poster EVO440 R.S. KOZLOV, A.V. DEKHNICH, M.V. SUKHORUKOVA, M.V. EDELSTEIN, A.V. CHERNAVIN, M.Y. SAMSONOV
2015 ATS
Efficacy and Safety of Oral Nemonoxacin in Treatment of Community-Acquired Pneumonia: Subgroup Analysis Results in Taiwanese Patients in a Randomized, Double-Blind, Multi-Center, Phase III Comparative Study with Levofloxacin – Poster 63714 S. L. CHENG, R. G. WU, Z. HSU, C. H. R. KING, P. HUANG, L. W. CHANG, J. YUAN, J. CHANG, P. T. HUANG, C. E. TSAI
2014 ICAAC
Meeting the Threat of Antibiotic Resistance: In Vitro Activity, Clinical Efficacy and Safety of Nemonoxacin, a Novel Non-Fluorinated Quinolone with QIDP Status – Poster L-1748b C. E. TSAI, Z. HSU, C. H. R. KING, P. HUANG, L. W. CHANG, J. YUAN, J. CHANG, P. T. HUANG, M. C. HSU
Efficacy and Safety of Oral Nemonoxacin in Treatment of Community-Acquired Pneumonia: Results from a Randomized, Double-Blind, Multiple-Center, Phase III Comparison Study with Levofloxacin– Poster L-1748c Y. Y. ZHANG, S. L. CHENG, C. E. TSAI, Z. HSU, C. H. R. KING, P. HUANG, L. W. CHANG, J. YUAN, J. CHANG, P. T. HUANG, M. C. HSU
2013 ICAAC
In Vitro Activity of Nemonoxacin, a Novel Quinolone Antibiotic, against Chlamydia pneumonia – Poster E-1182 K. CHOTIKANATIS, S. A. KOHLHOFF, M. R. HAMMERSCHLAG.
2010 ICAAC
Nemonoxacin for Treating Diabetic Foot Infections: An Open-Label, Single-Arm, Multiple-Center Study – Poster L1-344 B. A. LIPSKY, M. GANI, L. ROGERS, J. S. HWANG, D. T. CHUNG, C. Y. TSAI, L. W. CHANG, Y. T. CHANG, C. H. R. KING, M. C. HSU.
2008 ICAAC/IDSA
Comparative Antistaphylococcal activity of Nemonoxacin, a Novel Broad-spectrum Quinolone – Poster C1-189 G. A. PANKUCH, K. KOSOWSKA-SHICK, P. MCGHEE, C. R. KING , P. C. APPELBAUM .
In Vivo Efficacy of Nemonoxacin in a Mouse Protection Model – Poster B-1005 C. H. HSU, L. LIN, R. LEUNK, D. REICHART.
In Vivo Efficacy of Nemonoxacin in a Mouse Pulmonary Infection Model – Poster B-056 C. H. HSU, L. LIN, R. LEUNK, D. REICHART.
Efficacy and Safety of Nemonoxacin versus Levofloxacin for the Treatment of Community-Acquired Pneumonia – Poster L-678 D. J. VAN RENSBURG, R. P. PERNG, L. LIN, H. ZHANG.
In Vitro Resistance Development to Nemonoxacin for Streptococcus pneumoniae – Poster F1-2055 C. R. KING, L. LIN, R. LEUNK.
Fertility and Early Embryonic Developmental Toxicity of Nemonoxacin after Oral Administration to Rats – Poster F1-2056 C. H. HSU, Y. M. CHEN, C. P. CHOW.
Activity of Nemonoxacin, an Investigational C8-methoxy Non-fluorinated Quinolone Against Gram-Positive Cocci Obtained From Canadian Hospitals: CANWARD 2007 – Poster F1-2057 G. G. ZHANEL, M. LAING, M. DECORBY, K. NICHOL, C.H.R. KING, H. ADAM, D. J. HOBAN.
Activity of Nemonoxacin, an Investigational C8-methoxy Non-fluorinated Quinolone, Against Gram-Negative Bacilli Obtained From Canadian Hospitals: CANWARD 2007 – Poster C1-1957 N. LAING, M. DECORBY, K. NICHOL, C.H.R. KING, H. ADAM, D. J. HOBAN, G. G. ZHANEL.
In Vitro Activity of Nemonoxacin (TG-873870), a Novel Non-Fluorinated Quinolone, against Clinical Isolates of Streptococcus pneumoniae in Taiwan – Poster C2-254 P. R. HSUEH, C. KING.
In Vitro Activity of Nemonoxacin against Helicobacter pylori – Poster C2-3931 P.R. HSUEH, J. C. YANG, C. KING.
2008 WPCCID
A Randomized, Double-Blind, Comparative, Multiple-Center Study of Nemonoxacin versus Levofloxacin for the Treatment of Community-Acquired Pneumonia – Poster PS1-069 H. ZHANG, R. P. PERNG, D. J. J. VAN RENSBURG, L. LIN, H. C. TAN, L. W. CHANG.
Mutant Prevention Concentration of Nemonoxacin (TG-873870), a Novel Non-Fluorinated Quinolone, against Staphylococcus aureus – Poster PS1-066 Y. LIU, Z. LI, R. WANG, Z. ZHAO, M. C. HSU.
Comparative Antistaphylococcal activity of Nemonoxacin, a Novel Broad-spectrum Quinolone – Poster PS1-063 G. A. PANKUCH, K. KOSOWSKA-SHICK, C. R. KING , P. C. APPELBAUM.
In Vitro Antibacterial Activity of Nemonoxacin (TG-873870), a New Non-fluorinated Quinolone, Against Gram-Positive Pathogens – Poster PS1-065 T. L. LAUDERDALE, J. F. LAI, Y. R. SHIAU, H. C. CHEN, C. H. R. KING.
In Vitro Activity of Nemonoxacin (TG-873870) against Staphylococcus aureus, Enterococci, and Streptococcus pneumoniae with Various Resistant Phenotypes in Taiwan – Poster PS1-068 P. R. HSUEH, J. J. LU, C. H. R. KING.
2007 ICAAC
In Vitro Metabolism and Interaction of Nemonoxacin (TG-873870) on Human Hepatic CYP3A4 – Poster A-27 C. P. CHOW, C. Y. TSAI, C. F. YEH, S. J. CHEN.
Phototoxicity of Nemonoxacin (TG-873870) in Hairless Mice – Poster A-28 C. P. CHOW, C. SAMBUCO, A. M. HOBERMAN.
Cardiovascular Safety Evaluation of Nemonoxacin (TG-873870) in Dogs and Monkeys – Poster B-823 C. P. CHOW, C. Y. TSAI, Y. M. CHEN.
In Vitro Antibacterial Activity of Nemonoxacin (TG-873870), a New Non-Fluorinated Quinolone, against Clinical Isolates – Poster E-1635 T. L. LAUDERDALE, Y. R. SHIAU, J. F. LAI, H. C. CHEN, C. H. R. KING.
2007 IDSA
Single-Dose Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Non-Fluorinated Quinolone, in Healthy Volunteers – Poster 439 L. LIN, K. M. CHIU, T. K. CHUNG.
Multiple-Dose Study to Access the Safety, Tolerability and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Non-Fluorinated Quinolone, in Healthy Volunteers – Poster 440 H. ZHANG, K. M. CHIU, T. K. CHUNG, H. C. TAN, L. LIN .
Analysis of Antibacterial Response of Nemonoxacin (TG-873870) Against Major Pathogens from Respiratory Tract and Skin Infections – Poster 441 S. J. CHEN, L. LIN, L. W. CHANG.
Selected Publications
Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial. Yuan J, Mo B, Ma Z, Lv Y, Cheng SL, Yang Y, Tong Z, Wu R, Sun S, Cao Z, Wu J, Zhu D, Chang L, Zhang Y; Investigator Group of the Phase 3 Study on Oral Nemonoxacin. J Microbiol Immunol Infect. 2017 Aug 2. pii: S1684-1182(17)30151-2. doi: 10.1016/j.jmii.2017.07.011. [Epub ahead of print]
In vitro resistance development to nemonoxacin in Streptococcus pneumoniae: A unique profile for a novel nonfluorinated quinolone. Roychoudhury S, Makin K, Twinem T, Leunk R, Hsu MC. Microb Drug Resist. 2016 Oct;22(7):578-584.
Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin. Kocsis B, Domokos J, Szabo D. Ann Clin Microbiol Antimicrob. 2016 May 23;15(1):34. doi: 10.1186/s12941-016-0150-4. Review.
Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers. Zhang YF, Dai XJ, Yang Y, Chen XY, Tang YB, Tsai CY, Chang LW, Chang YT, Zhong DF. Drug Design, Development and Therapy 2016:10 357-370.
A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia. Liu Y, Zhang Y, Wu J, Zhu D, Sun S, Zhao L, Wang X, Liu H, Ren Z, Wang C, Xiu Q, Xiao Z, Cao Z, Cui S, Yang H, Liang Y, Chen P, Lv Y, Hu C, Lv X, Liu S, Kuang J, Li J, Wang D, Chang L. J Microbiol Immunol Infect. 2017 Dec;50(6):811-820.
Pharmacokinetics and pharmacodynamics of multiple-dose intravenous nemonoxacin in healthy Chinese volunteers. Wu XJ, Zhang J, Guo BN, Zhang YY, Yu JC, Cao GY, Chen YC, Zhu DM, Ye XY, Wu JF, Shi YG, Chang LW, Chang YT, Tsai CY. Antimicrob Agents Chemother. 2015 Mar;59(3):1446-1454.
The potential role of nemonoxacin for treatment of common infections. Huang CH, Lai CC, Chen YH, Hsueh PR. Expert Opin Pharmacother. 2015 Feb;16(2):263-270.
Effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers. Zhang YF, Dai XJ, Wang T, Chen XY, Liang L, Qiao H, Tsai CY, Chang LW, Huang PT, Hsu CY, Chang YT, Tsai CE, Zhong DF. Acta Pharmacol Sin. 2014 Dec;35(12):1586-1592.
Determination of a novel nonfluorinated quinolone, nemonoxacin, in human feces and its glucuronide conjugate in human urine and feces by high-performance liquid chromatography-triple quadrupole mass spectrometry. He G, Guo B, Yu J, Zhang J, Wu X, Cao G, Shi Y, Tsai CY. Biomed Chromatogr. 2015 May;29(5):739-748.
Antibacterial activities of nemonoxacin against clinical isolates of Staphylococcus aureus: an in vitro comparison with three fluoroquinolones. Li Z, Liu Y, Wang R, Li A. World J Microbiol Biotechnol. 2014 Nov;30(11):2927-2932.
Safety, tolerability, and pharmacokinetics of intravenous nemonoxacin in healthy chinese volunteers. Cao GY, Zhang J, Zhang YY, Guo BN, Yu JC, Wu XJ, Chen YC, Wu JF, Shi YG. Antimicrob Agents Chemother. 2014 Oct;58(10):6116-21.
Review of nemonoxacin with special focus on clinical development. Qin X, Huang H. Drug Des Devel Ther. 2014 Jul 5;8:765-74.
Nemonoxacin (TG-873870) for treatment of community-acquired pneumonia. Lai CC, Lee KY, Lin SW, Chen YH, Kuo HY, Hung CC, Hsueh PR. Expert Rev Anti Infect Ther. 2014 Apr;12(4):401-17.
In vitro activity of nemonoxacin, a novel nonfluorinated quinolone antibiotic, against Chlamydia trachomatis and Chlamydia pneumoniae. Chotikanatis K, Kohlhoff SA, Hammerschlag MR. Antimicrob Agents Chemother. 2014;58(3):1800-1801.
Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006-2010. Chen YH, Liu CY, Ko WC, Liao CH, Lu PL, Huang CH, Lu CT, Chuang YC, Tsao SM, Chen YS, Liu YC, Chen WY, Jang TN, Lin HC, Chen CM, Shi ZY, Pan SC, Yang JL, Kung HC, Liu CE, Cheng YJ, Liu JW, Sun W, Wang LS, Yu KW, Chiang PC, Lee MH, Lee CM, Hsu GJ, Hsueh PR. Eur J Clin Microbiol Infect Dis. 2014 Feb;33(2):233-239.
Pharmacokinetics and Pharmacodynamics of Nemonoxacin against Streptococcus pneumoniae in an In Vitro Infection Model. Liang W, Chen YC, Cao YR, Liu XF, Huang J, Hu JL, Zhao M, Guo QL, Zhang SJ, Wu XJ, Zhu DM, Zhang YY, Zhang J. Antimicrob Agents Chemother. 2013 Jul;57(7):2942-7.
Safety and clinical pharmacokinetics of nemonoxacin, a novel non-fluorinated quinolone, in healthy chinese volunteers following single and multiple oral doses. Guo B, Wu X, Zhang Y, Shi Y, Yu J, Cao G, Zhang J. Clin. Drug Invest. 2012 Jul 1;32(7):475-486.
Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: A Multicenter Study in Taiwan. Liao CH, Ko WC, Lu JJ, Hsueh PR. Antimicrob Agents Chemother. 2012 Jul;56(7):3943-3949.
A liquid chromatography-tandem mass spectrometry assay for the determination of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, in human plasma and urine and its application to a single-dose pharmacokinetic study in healthy Chinese volunteers. Guo B, Zhang J, Yu J, Wu X, Shi Y, Tsai CY. Biomed Chromatogr. 2012 Nov;26(11):1333-1140.
Multicenter Study In Taiwan of the In Vitro Activities of Nemonoxacin, Tigecycline, Doripenem, and Other Antimicrobial Agents against Clinical Isolates of Various Nocardia Species. Lai CC, Liu WL, Ko WC, Chen YH, Tan HR, Huang YT, Hsueh PR. Antimicrob Agents Chemother. 2011 May; 55(5):2084-2091.
In vitro susceptibilities of clinical isolates of ertapenem-non-susceptible Enterobacteriaceae to nemonoxacin, tigecycline, fosfomycin and other antimicrobial agents. Hsu MS, Liao CH, Liu CY, Yang CJ, Huang YT, Hsueh PR. Int J Antimicrob Agents. 2011 Mar;37(3):276-278.
Antimicrobial Susceptibilities and Molecular Epidemiology of Clinical Isolates of Clostridium difficile in Taiwan. Lin YC, Huang YT, Tsai PJ, Lee TF, Lee NY, Liao CH, Lin SY, Ko WC, Hsueh PR. Antimicrob Agents Chemother. 2011 Apr; 55(4);1701-1705.
In vivo antibacterial activity of nemonoxacin, a novel non-fluorinated quinolone. Li CR, Li Y, Li GQ, Yang XY, Zhang WX, Lou RH, Liu JF, Yuan M, Huang P, Cen S, Yu LY, Zhao LX, Jiang JD, You XF. J Antimicrob Chemother. 2010 Nov;65(11):2411-2415.
Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia. Dirkie J. J. van Rensburg, Reury-Perng Perng, Ismail H. Mitha, Andrè J.Bester, Joseph Kasumba, Ren-Guang Wu, Ming-Lin Ho, Li-Wen Chang, David T. Chung, Yu-Ting Chang,Chi-Hsin R. King, and Ming-Chu Hsu. Antimicrob Agents Chemother. 2010 Oct;54(10):4098-4106.
In vitro activity of nemonoxacin, tigecycline, and other antimicrobial agents against Helicobacter pylori isolates in Taiwan, 1998-2007. Yang JC, Lee PI, Hsueh PR. Eur J Clin Microbiol Infect Dis. 2010 Nov;29(11):1369-1375.
Comparative in vitro activities of nemonoxacin, (TG-873870), a novel nonfluorinated quinolone, and other quinolones against clinical isolates. Tsai-Ling Lauderdale, Yih-Ru Shiau, Jui-Fen Lai, Hua-Chien Chen, and Chi-Hsin R. King. Antimicrob Agents Chemother. 2010 Mar; 54(3):1338-42.
Multiple-Dose Safety, Tolerability, and Pharmacokinetics of Oral Nemonoxacin (TG-873870) in Healthy Volunteers. David T. Chung, Cheng-Yuan Tsai, Shu-Jen Chen, Li-Wen Chang, Chi-Hsin R. King, Ching-Hung Hsu, Kit-Mui Chiu, Hao-Chen Tan, Yu-Ting Chang, and Ming-Chu Hsu. Antimicrob Agents Chemother. 2010 Jan; 45(1):411-417.
Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Nemonoxacin (TG-873870), a Novel Potent Broad-Spectrum Non-Fluorinated Quinolone, in Healthy Volunteers. Luke Lin, Li-Wen Chang, Cheng-Yuan Tsai, Ching-Hung Hsu, David T. Chung, William S. Aronstein, Funmi Ajayi, Barbara Kuzmak, and Robert A. Lyon. Antimicrob Agents Chemother. 2010 Jan;45(1):405-410.
In vitro activity of nemonoxacin (TG-873870), a novel non-fluorinated quinolone, against clinical isolates of Staphylococcus aureus, Enterococci, and Streptococcus pneumoniae with various resistant phenotypes in Taiwan. Yeh-Hsu Chen, Chia-Ying Liu, Jang-Jih Lu, Chi-Hsin R. King, and Po-Ren Hsueh. J Antimicrob Chemother. 2009 Dec;64(6):1226-1229.
Comparative in vitro activities of the new quinolone nemonoxacin (TG-873870), gemifloxacin and other quinolones against clinical isolates of Mycobacterium tuberculosis. Che-Kim Tan, Chih-Cheng Lai, Chun-Hsing Liao, Chien-Hong Chou, Hsiao-Leng Hsu, Yu-Tsung Huang and Po-Ren Hsueh. J Antimicrob Chemother. 2009 Aug;64(2):428-429.
Comparative in vitro activities of nemonoxacin, doripenem, tigecycline and 16 other antimicrobials against Nocardia brasiliensis, Nocardia asteroides and unusual Nocardia species. Chih-Cheng Lai, Che-Kim Tan, Sheng Hsiang Lin, Chun-Hsing Liao, Chien-Hong Chou, Hsiao-Leng Hsu, Yu-Tsung Huang, and Po-Ren Hsueh. J Antimicrob Chemother. 2009 Jul;64(1):73-78.
Nemonoxacin. Arjona, A, Castaner, R, Bolos, J. Drugs of the Future. 2009 Mar; 34(3): 196-203.
