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药品名称：Revestive Contact address: Product details
Publication details
NPS Pharma Holdings Limited Grand Canal House 1 Grand Canal Street Upper Dublin 4 Ireland Revestive 5 mg Pulver und Lösungsmittel zur Herstellung einer Injektionslösung - OP[28x(27.96mg+0.5ml)]; Pulver und Lösungsmittel zur Herstellung einer Injektionslösung; Nycomed Danmark A/S Allgemeine Angaben Eingangsnummer : 2709727 Arzneimittelname: Revestive 5 mg Pulver und Lösungsmittel zur Herstellung einer Injektionslösung - OP[28x(27.96mg+0.5ml)] Darreichungsform : Pulver und Lösungsmittel zur Herstellung einer Injektionslösung Administrative Daten Antragsteller: Nycomed Danmark A/S Verkehrsfähig : ja Zulassungs-/Reg-Nr.(AMG76) : EU/1/12/787/001 Zusammensetzung Arzneilich wirksame Bestandteile ASK-Nr. Stoffname Stoffmenge Teduglutid 5.mg Changes since initial authorisation of medicine
Initial marketing-authorisation documents
Generic Name: teduglutide Trade Name: Revestive (EU), Gattex (US) Synonym: ALX 0600, [gly2]-recombinant human glucagon-like peptide, Gattex Entry Type: New molecular entity Developmental Status UK: Launched EU: Launched US: Launched UK launch Plans: Available only to registered users Actual UK launch date: September 2014 Comments Sep 14: Launched in the UK. 5mg vial plus solvent, 28=£14,615.39 [33]. 17/09/2014 13:15:10 Mar 14: Marketed in the US [32] 24/03/2014 16:21:00 Nov 13: Supplemental New Drug Application submitted in the US to include long-term data from STEPS 2 in the product label. A decision by the FDA is expected by June 28, 2014 [31]. 17/11/2013 17:16:44 Aug 13: The company plans to launch in Europe in the first half of 2014 [29] 26/08/2013 11:02:53 Mar 13: NPS Pharmaceuticals has re-gained the full worldwide rights to teduglutide. The cost of teduglutide in the US is $295,000 a year. NPS will be marketing the drug in Europe [28]. 20/03/2013 19:28:06 Dec 12: Approved in US for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. Gattex will be available in Q1 2013. [27] 23/12/2012 19:01:28 Oct 12: FDA panel vote in favour of approval [26]. 18/10/2012 08:17:37 Oct 12: FDA staff issue a favourable review prior to the advisory panel meeting and endorse the company´s risk mitigation strategy. The FDA review notes that there are three key safety concerns, gastrointestinal obstructions, the growth of polyps and pancreatic disorders, but concludes that the drug´s use would not need to be restricted due to these concerns. Under the proposed REMS, doctors would be advised against prescribing the drug to any patient with active cancer, patients would need to be cancer-free for 5 years, all patients would have to undergo a colonoscopy within 6 months of beginning treatment and any polyps found should be removed during the procedure. A patient registry could gather long-term responses to the drug and, like most REMS programmes, physicians would need to complete an education program on risks. And the company proposes to help manage risk with a direct patient support programme [25]. 13/10/2012 17:15:42 Sep 12: Marketing authorisation approved in the EU [24]. 04/09/2012 21:23:32 Aug 12: Application will be discussed at the FDA´s Gastrointestinal Drugs Advisory Committee meeting scheduled for Oct 16, 2012 [23]. 28/08/2012 09:00:40 Aug 12: FDA decision date delayed to 30 Dec 12 [22]. 13/08/2012 16:45:58 Jun 12: EU positive opinion [21]. 22/06/2012 16:02:25 May 12: FDA decision expected by 28 Sep [20]. 16/05/2012 17:42:29 Jan 12: FDA has accepted and filed for review [19]. 01/02/2012 15:17:52 Dec 11: Company has completed the submission of a New Drug Application (NDA) to the FDA and has asked for a priority review [18]. 01/12/2011 21:58:54 Aug 11: Company has started a rolling submission of evidence to support the NDA in the US [16] 19/08/2011 12:43:48 March 11: Marketing Authorisation Application submitted to the EMA for approval of teduglutide as a once-daily subcutaneous treatment for short bowel syndrome (SBS). [14] 29/03/2011 10:19:11 Jan 11: Filing planned for 1H 2011 in EU and 2H 2011 in US [13]. 31/01/2011 19:30:03 The US FDA recommended that the company should conduct a confirmatory PIII trial of teduglutide for SBS prior to the submission of a NDA for the drug. The STEPS trial is now underway (8). 24/03/2009 16:22:43 Orphan drug status in EU since Dec 01 (6) 11/04/2008 13:00:57 PIII in US with orphan drug status. Pivotal PIII study started in pts with short bowel syndrome (1). Trial or other data Oct 13: New findings from STEPS 2, two-year open-label study: Investigators report long-term use of Gattex in pts with SBS resulted in additional, clinically meaningful reductions in the volume and days per week of parenteral support requirements in this extension study. In addition, 10 of the 13 pts who achieved complete independence from parenteral support were those who received 30 months of Gattex in the 6-month STEPS pivotal study and the 24-month STEPS 2 study. Two pts who received placebo in STEPS and 24 months of Gattex in STEPS 2 and one pt who bypassed STEPS and was enrolled directly into STEPS 2 also achieved independence from parenteral support. [3] 16/10/2013 15:50:26 Nov 11: In the STEPS 2 study, there were three cases of cancer, two of which resulted in death, reported at two sites in Poland. These cases have been reviewed by a safety review board & no changes in study design or current monitoring of subjects in the trial have been requested [17]. 02/11/2011 10:15:32 Oct 11: Data from long-term, open-label STEPS 2 study. Teduglutide was associated with achieving and maintaining clinically meaningful reductions in parenteral nutrition and IV fluid volume in adult subjects with short bowel syndrome. Primary study objective was to assess long-term safety and durability of effect in 76 subjects who completed, participated in, or qualified for participation in STEPS. 91% responded after 12 months of teduglutide, i.e. had a 20-100% reduction in PN/IV volume from baseline. 24% of subjects reduced their infusion days per week by 3 or more days after 12 months of therapy. Three subjects participating in STEPS 2 were able to gain complete independence from and discontinue PN/IV fluids. [16] 01/11/2011 08:47:00 Jan 11: The PIII pivotal STEPS study met the primary efficacy endpoint defined as the % of patients who achieved a ≥20% reduction in weekly PN volume at weeks 20 and 24 vs baseline. In an ITT analysis, 63% (27/43) of teduglutide-treated patients responded vs 30% (13/43) on placebo (p=0.002). Patients treated with teduglutide for 24 weeks also achieved significantly greater reductions in weekly PN volume (4.4L reduction from a pre-treatment baseline of 12.9L) vs placebo (2.3L reduction from a pre-treatment baseline of 13.2L (p ≤0.001). 4 of 86 randomized patients discontinued the study due to AEs (one on teduglutide and 3 on placebo) [13]. 31/01/2011 19:30:35 Jan 11: The PIII STEPS has completed the 24-week treatment period. NPS is also advancing STEPS 2, an open-label continuation study in which all participants will receive up to an additional 24 months of therapy. 97% of eligible patients who completed STEPS elected to enroll in STEPS 2 [12]. 14/01/2011 15:31:51 Jul 10: The confirmatory 24 week placebo-controlled study PIII STEPS study (NCT00798967) has completed its enrolment of 86 patients with parenteral nutrition-dependent short bowel syndrome. The study is due to complete Dec 10. The primary outcome is the proportion of patients who demonstrate a response (≥20% reduction in weekly parenteral nutrition volume) at week 20 and maintain that response to week 24. The company intend to report the results to the FDA early 2011 and file an NDA soon after [11]. 23/07/2010 21:53:00 Oct 09: Further results from the PIII study (n=83) were presented at the American College of Gastroenterology 2009 Meeting. Data from the 24-week study showed that teduglutide significantly improved lean body mass and total bone mineral content in PN-dependent SBS patients (Abstract P272). These effects are desirable as patients are prone to malnutrition, dehydration and osteoporosis. A separate presentation showed that teduglutide improves intestinal electrolyte and wet weight absorption in SBS patients. However, there was no significant correlation between these improvements and levels of plasma citrulline, which was being investigated as a biomarker of gut function (Abstract P273) [10]. 28/10/2009 08:43:13 Jun 09: The company expects to complete patient enrolment in the confirmatory PIII STEPS trial before the end of the Q1 2010 (9) 09/06/2009 17:59:01 Jun 09: Further data from the 24 week PIII study in 83 patients with SBS who were dependent on parenteral nutrition (PN) (described below) were presented at the Digestive Disease Week Congress. In the original analysis, teduglutide failed to meet its primary endpoint as the high dose arm (0.10mg/kg/day) did not reduce the need for PN by at least 20% vs. baseline to weeks 16 and weeks 24, although in the low dose arm (0.05mg/kg/day), 46% of patients achieved a statistically significant reduction of PN vs. placebo (p=0.007). The recent data include a study in a subpopulation of 21 patients in whom teduglutide decreased faecal wet weight by 735±574g/d vs. baseline (p=0.006), decreased sodium loss by 49±30 mm/L/day (p<0.001) and decreased potassium loss by 19±22 mm/L/d (p=0.003). In a second substudy, patients who exhibited an increase in endogenous non-protein amino-acid citrulline levels at week 8 were likely to achieve a significant response to teduglutide, suggesting that citrulline represents a good biomarker (9). 09/06/2009 17:58:49 Dec 08: STEPS (Study of TEduglutide in PN-dependent Short-bowel syndrome) PIII study in patients with SBS commenced. The study will have an initial three to eight week PN optimization and stabilization period, after which patients will be randomised to receive SC teduglutide 0.05 mg/kg or placebo daily for 24 weeks. The primary efficacy measure will be the percentage of patients who achieve a 20% or greater reduction in weekly PN volume at week 20 and maintain that response at week 24 compared with baseline (8). 24/03/2009 16:23:57 Oct 08: Results of a P3 28 wk, extension study presented at the American College of Gastroenterology Annual Scientific Meeting. The study enrolled 65 of 71 patients who had completed a 24-week randomised P3 study of low-dose teduglutide 0.05 mg/kg/day or high-dose teduglutide 0.10 mg/kg/day vs. placebo. Patients who received placebo in the original study received teduglutide in the extension study. There were no major differences in safety (primary endpoint) between groups except for a higher rate of injection site reactions with high-dose teduglutide. 12 of 16 patients, and 6 of 8 patients, who had responded to low-dose and high-dose teduglutide, respectively, maintained their response in the extension phase, with 10 and 2 patients, respectively, achieving further reductions in parenteral nutrition volumes. A mean weekly reduction in parenteral nutrition of 4.9L and 3.3L was achieved with low and high dose teduglutide (7). 19/10/2008 16:02:08 Failed to meet primary endpoint in clinical study but lower dose showed benefit (5) 27/03/2008 10:51:08 s.c. inj shown to stimulate intestinal lining growth and nutrient absorption. PIII studies designed to show reduction in use of IV feeding(2). 80 pts PIII double-blind efficacy study -randomised to receive 0.05 or 0.10 mg/kg/day of teduglutide, or a placebo for six months, with a six-month follow up study (3). 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