太景抗感染新藥 年底兩岸開賣 布局海外市場 授權中、俄、土耳其等 2015年05月22日F*太景董事長許明珠表示，抗細菌感染新藥將於兩岸率先全球開賣。【黃馨儀╱台北報導】F*太景(4157)昨舉行業績發表會，董事長暨執行長許明珠表示，新藥研發專注於抗感染及抗腫瘤領域，均名列全球前10大疾病用藥類別。其中，抗細菌感染新藥太捷信R率先報佳音，最快年底於兩岸率先開賣。 而幹細胞驅動劑布利沙福正陸續與國內外重要醫學機構合作開發適應症；C型肝炎蛋白抑制劑TG-2349，則以開發出療效顯著、藥價合理，且副作用低的雞尾酒療法為目標，嘉惠全球C肝病患。抗感染抗腫瘤需求大 F*太景旗下產品包括獲得台灣首例全新小分子新藥上市許可證的新一代抗生素太捷信R、幹細胞驅動劑布利沙福及抗C肝病毒藥物TG-2349。 許明珠表示，抗感染與抗腫瘤相關醫藥領域的藥品需求都炙手可熱，根據IMS統計，抗感染藥品2014年全球市場規模403億美元(約1.24兆元台幣)，抗腫瘤藥品市場更達744億美元(約2.28兆台幣)。 許明珠指出，由於太捷信R是大中華區唯一獲美國FDA(Food and Drug Administration，食品藥物管理局)資格的抗感染藥物，將在年底兩岸開賣。太捷信R口服劑型已獲台灣藥品許可證，現正申請健保核價程序，取得核價後即可銷售。 至於太捷信R在國外市場部分，已授權給中國浙江醫藥外，俄羅斯、土耳其及獨立國協等市場，也已授權俄羅斯藥廠R-Pharm，公司也積極洽談其他地區授權。而另外一新藥布利沙福，則可望取代既有自體與異體造血幹細胞動員藥物，並開發針對血液腫瘤與轉移性固體腫瘤，包含乳癌、攝護腺癌等的化療增敏適應症。 至於抗C肝病毒藥物TG-2349，則設計搭配與干擾素與雷巴威林的療法，針對好發於華人的病毒基因Ib型病人，將療程縮短到8周以下，已向中國申請1.1類新藥IND，擴大到第一基因型以外的病患。【F*太景(4157)小檔案】 董事長：許明珠 資本額：2024萬元 ●主要產品： ◎癌症相關藥物，如太捷信R、幹細胞驅動劑布利沙福 ◎抗C肝病毒藥物TG-2349 ●首季財報： ◎營收1879萬元 ◎稅後虧損8464萬元 ◎每股虧損0.12元 ●近期布局： ◎太捷信R最快年底兩岸開賣，並與俄藥廠洽談授權 ◎布利沙福擬針對血液腫瘤與轉移性固體腫瘤，包含乳癌、攝護腺癌進行應用開發 資料來源：公開資訊觀測站、業者、記者整理
A Phase 2, Multicenter, Randomized, Open-label, Dose-ranging Study to Evaluate the Efficacy and Safety of TG-2349 in Combination with Peg-interferon and Ribavirin in Treatment Naïve East Asian Subjects with Chronic Hepatitis C Virus Genotype 1b Infection.
Primary Outcome Measures: Antiviral efficacy of TG-2349 in combination with Peg-interferon (IFN) and Ribavirin (RBV) in treatment naïve East Asian subjects with HCV GT1b infection [ Time Frame: 12 weeks after the end of treatment (SVR12), after 12 to 24 weeks treatments ] [ Designated as safety issue: No ]Antiviral efficacy is measured by the proportion of subjects with HCV RNA< LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at 12 weeks after the end of treatment (SVR12) in the Full Analysis Set (FAS) population, which include subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.
Estimated Enrollment: 48 /Study Start Date: January 2015 /Estimated Study Completion Date: June 2017 /Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
The study is divided into two parts: Part A: Part A is a multicenter, randomized, open-label study to evaluate the safety, tolerability, and antiviral efficacy of two different doses of TG-2349 combined with Peg-interferon (IFN) and Ribavirin (RBV) in HCV-GT1b treatment naïve East Asian subjects. The treatment duration of TG-2349+IFN+RBV is 12 weeks, with or without an additional 12-week treatment of IFN+RBV, depending on HCV RNA level at On-Treatment Week 4. Approximately 24 subjects will be randomized (1:1) to one of the following 2 treatment groups:
Group I (n=12): 200 mg TG-2349 (2 capsules) + IFN + RBV
Group II (n=12): 400 mg TG-2349 (4 capsules) + IFN + RBV Randomization will be stratified by IL28B genotype "CC" or "non-CC". Subjects with HCV RNA < LLOQ (lower limit of quantification), TD (target detected) or TND (target not detected) at Week 4 will receive 12 weeks of TG-2349+IFN+RBV treatment. Subjects with HCV RNA ≥ LLOQ but < 100 IU/mL at Week 4 will receive 12 weeks of TG-2349+IFN+RBV treatment followed by an additional 12 weeks of IFN+RBV treatment. However, subjects with HCV RNA ≥ 100 IU/mL at Week 4 will discontinue the study treatment and complete the Early-Termination (ET) visit. The study will be terminated if 3 or more of the first 12 subjects enrolled across both Groups I and II, or ≥ 25% of subjects thereafter, fail to respond to treatment (i.e., confirmed on-treatment virologic failure or post-treatment relapse). Patients, except those who have achieved SVR12, will be offered the standard of care with Peg-interferon and Ribavirin for duration of 24, 48, or 72 weeks based on Taiwan's regulatory guideline and principal investigator's judgment.
Part B: Based on the preliminary safety data and SVR 4 efficacy data obtained from Part A, one or two optimal dose(s) of TG-2349 will be selected for Part B in order to evaluate the antiviral efficacy of 8-week treatment of TG-2349 +IFN+RBV, with or without an additional 12-week treatment of IFN+RBV, depending on the HCV RNA level at On-Treatment Week 4. Approximately 12 subjects per dose group will be enrolled. Subjects with HCV RNA < LLOQ, TND at Week 4 will receive 8 weeks of TG-239+IFN+RBV treatment. Subjects with HCV RNA ≥ LLOQ, TND but < 100 IU/mL at Week 4 will receive 8 weeks of TG-2349+IFN+RBV treatment followed by an additional 12 weeks of IFN+RBV treatment. However, subjects with HCV RNA ≥ 100 IU/mL at Week 4 will discontinue the study treatment and complete the Early-Termination (ET) visit. Part B study will be terminated if ≥ 25% of subjects fail to respond to treatment (i.e., confirmed on-treatment virologic failure or post-treatment relapse). Patients, except those who have achieved SVR12, will be offered the standard of care with Peg-interferon and Ribavirin for duration of 24, 48, or 72 weeks based on Taiwan's regulatory guideline and principal investigator's judgment.
Inclusion Criteria: Willing and able to provide written informed consent. East Asian subjects, male or female, and age between 18 (or legal adult age) and 70 years, inclusive, at Baseline/Day 1. Body mass index (BMI) in the range of 18.0 to 35.0 kg/m2 (inclusive) and body weight ≥ 40 kg. Presence of chronic hepatitis C (CHC) as documented below: (1) A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit or (2) A liver biopsy or FibroTest performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection, such as the presence of fibrosis and/or inflammation. 5. Positive for anti-HCV antibody at Screening. 6. Presence of an HCV RNA level ≥ 1 x 10000 IU/mL at Screening as determined by the Central Laboratory. 7. Presence of genotype 1b HCV-infection at Screening as determined by the Central Laboratory. Any non-definitive results will exclude the subject from study participation. 8. HCV treatment naïve defined as no prior therapy with any interferon (IFN), ribavirin (RBV), or other approved or investigational HCV-specific agent. 9. Absence of cirrhosis
Cirrhosis as defined as any one of the following:
Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥ 5).
FibroScan showing cirrhosis or results > 12.5 kPa.
FibroTest fibrosis score of > 0.58 and APRI (AST: platelet ratio index) of > 2 during Screening. If no definitive diagnosis of cirrhosis by the above criteria, a liver biopsy is required; liver biopsy results will supersede non-invasive testing results and be considered definitive. 10. Screening ECG without clinically significant abnormalities. 11. Subjects must have the following laboratory parameters at Screening: ALT ≤ 10 × the upper limit of normal (ULN) AST ≤ 10 × ULN Total bilirubin ≤ 1.5 × ULN except history of Gilbert's syndrome. If Gilbert's syndrome is the proposed etiology, the total bilirubin must ≤ 2 × ULN. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 Platelet count ≥ 90,000 cells/mm3 HbA1c ≤ 8.5% Thyroid stimulating hormone (TSH) and T4 ≤ ULN Creatinine clearance (CLcr) ≥ 60 mL /min, as calculated by the Cockcroft-Gault equation Serum creatinine ≤ 1.5 × ULN Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects Albumin ≥ 3.5 g/dL INR (International Normalized Ratio for Prothrombin Time) ≤ 1.5 x ULN unless subject is stable on an anticoagulant regimen affecting INR Anti-nuclear antibodies (ANA) ≤ 1:320. 12. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by Investigator. 13. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments, including all required Post-Treatment visits. 14. A female subject is eligible to enter the study if it is confirmed that she is: (1) Not pregnant or nursing. (2) Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal - women > 50 years of age with cessation (for ≥12 months) of previously occurring menses), or (3) Of childbearing potential (i.e., women who have not had a hysterectomy, have not had both ovaries removed, and have not had medically documented ovarian failure). Women ≤ 50 years of age with amenorrhea will be considered to be of childbearing potential. These women must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at the Baseline/Day 1 visit prior to randomization. They must also agree to one of the following from Screening until 6 months after the last dose of study drug(s): - Complete abstinence from intercourse. Periodic abstinence from intercourse (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not permitted. Or - Consistent and correct use of 1 of the following methods of birth control listed below, in addition to a male partner who correctly uses a condom, from Screening until 6 months after the last dose of study drug(s): intrauterine device (IUD) with a failure rate of < 1% per year female barrier method: cervical cap or diaphragm with spermicidal agent tubal sterilization vasectomy in male partner hormone-containing contraceptive: i. implants of levonorgestrel ii. injectable progesterone iii. oral contraceptives (either combined or progesterone only) iv. contraceptive vaginal ring v. transdermal contraceptive patch. 15. Male subjects must agree to consistently and correctly use a condom, while their female partner agrees to use 1 of the methods of birth control listed above, from Screening until 6 months after the last dose of study drug(s). 16. Male subjects must agree to refrain from sperm donation from Screening until at least 6 months after the last dose of study drug(s).
Exclusion Criteria: Presence of cirrhosis. Positive serological test for IgM anti-HAV (hepatitis A virus) antibody or HBsAg at Screening. Positive ELISA test for HIV-1 or HIV-2 at Screening. Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson disease, alfa-1 antitrypsin deficiency, cholangitis). Donation or loss of more than 400 mL blood within 2 months prior to Baseline/Day 1. Clinically-relevant drug abuse within 12 months of Screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by Investigator. Alcohol misuse as defined by an AUDIT score of ≥ 8. Contraindications to RBV or IFN therapy, including hemoglobinopathies (e.g., thalassemia major or sickle-cell anemia), autoimmune thyroiditis or other autoimmune disorders including autoimmune hepatitis. Pregnant or nursing female or male with pregnant female partner. Use of any prohibited medications within 30 days of the Baseline/Day 1 visit: (1) Hematologic stimulating agents (e.g., erythropoiesis-stimulating agents [ESAs], granulocyte colony stimulating factor [G-CSF], and thrombopoietin [TPO] mimetics) (2) Chronic use of systemic immunosuppressants including, but not limited to, corticosteroids (prednisone equivalent of > 10 mg/day for > 2 weeks), azathioprine, or monoclonal antibodies (eg, infliximab) (3) Investigational agents or devices for any indication (4) Drugs disallowed per prescribing information of RBV or IFN (5) Any prohibited medications listed in Table 6-2. 11. Known hypersensitivity to RBV, IFN, TG-2349, sulfa drugs, or formulation excipients. 12. Current or prior history of any of the following: Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded. Gastrointestinal disorder or post operative condition that could interfere with the absorption of the study drugs. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage). Central nervous system (CNS) trauma, seizure disorder, stroke or transient ischemic attack. Solid organ transplantation. Significant cardiac disease (including but not limited to the myocardial infarction based on ECG and/or clinical history). Significant pulmonary disease or porphyria.
Clinically significant retinal disease. Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years. Subjects with psychiatric illness (without the prior mentioned conditions) that is well-controlled on a stable treatment regimen for at least 12 months prior to Baseline/Day 1 or has not required medication in the last 12 months may be included.
Malignancy within 5 years prior to Screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
Drug: TG-2349 TG-2349 (Furaprevir) is available as a Swedish orange capsule (size 0) for oral administration. Each capsule contains an equivalent of 100 mg of TG-2349 spray dried solid (SDD) and the following inactive ingredients: microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, magnesium stearate, and colloidal silicon oxide.
Drug: Ribavirin RBV (Ribavirin or COPEGUS®) is available as a light pink to pink colored, flat, oval-shaped, film-coated tablet for oral administration. Each tablet contains 200 mg of ribavirin and the following inactive ingredients: pregelatinized starch, microcrystalline cellulose, sodium starch glycolate, cornstarch, and magnesium stearate. The coating of the tablet contains Chromatone-P® or Opadry® Pink (made by using hydroxypropyl methyl cellulose, talc, titanium dioxide, synthetic yellow iron oxide, and synthetic red iron oxide), ethyl cellulose (ECD-30), and triacetin.
Drug: Interferon Alfa-2a IFN (Interferon, Peg-interferon alpha-2a or PEGASYS®) is available as a sterile, preservative-free, colorless to light yellow injectable solution administered subcutaneously.
Each prefilled syringe of 180 μg/0.5 mL IFN (expressed as the amount of interferon alfa-2a) also contains acetic acid (0.0231 mg), benzyl alcohol (5 mg), polysorbate 80 (0.025 mg), sodium acetate trihydrate (1.3085 mg), and sodium chloride (4 mg) at pH 6 ± 0.5.
TG-2349，正在美國進行I/II期臨床試驗。與既有的藥物相比，TG-2349的競爭優勢包括：(1)可對抗6種基因型之C肝病毒，(2)安全性高，(3)每日僅需口服一次，(4)無須與干擾素並用，可避免干擾素帶給病患的強烈不適根據在美國與台灣進行的Phase I/IIa臨床試驗顯示，病患口服三天TG-2349，每日一次，血中病毒濃度即大幅降至原來的萬分之一。台灣病患接續以健保給付的干擾素與雷巴威林進行治療，四周後即偵測不到病毒。太景的目標在將現有治療C肝標準之24週療程，縮短到8週，甚至更短，如此將可大幅減輕病患的副作用，並讓病人與保險機構負擔得起。太景也已向中國申請TG-2349的1.1類新藥IND，將擴大到第一基因型以外的病患。
See also...太景口服C肝藥TG-2349 Phase I/IIa成關鍵
