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
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• SBS is a rare and highly disabling condition that impacts patients’ quality of life and can lead to serious life-threatening complications
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• Teduglutide has received orphan drug designation for the treatment of SBS from the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA)
Osaka, Japan and Bedminster, NJ, September 4, 2012 --- Takeda Pharmaceutical Company Limited (TSE:4502, “Takeda”) and NPS Pharmaceuticals, Inc. (NASDAQ: NPSP, “NPS”), jointly announced today that the European Commission (EC) has granted European market authorization for the medicinal product teduglutide (trade name in Europe: Revestive®) as a once-daily treatment for adult patients with short bowel syndrome. The marketing authorization follows a positive opinion issued on June 21, 2012, by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). Following the authorization, Takeda intends to provide patient access to Revestive® within Europe initially through a Named Patient Program (NPP) *.
“Short Bowel Syndrome patients suffer from malnutrition and diarrhoea, and often parenteral nutrition is necessary to maintain life,” said Professor Palle Bekker Jeppesen, M.D., Ph.D, Department of Medical Gastroenterology, Rigshospitalet, University Hospital of Copenhagen, Denmark. “Revestive is a new, unique and important treatment option for our patients and is adding important value to the limited treatment armamentarium.”
“Teduglutide is the first approved treatment in Europe for this debilitating disease and offers an important new treatment option to patients who are reliant on parenteral nutrition.” said Trevor Smith, Head of Commercial Operations, Europe & Canada, of Takeda.
“The granting of European marketing authorisation for teduglutide is welcome news for patients who suffer from short bowel syndrome,” said Francois Nader, MD, President and Chief Executive Officer of NPS Pharmaceuticals. “We look forward to supporting our partner Takeda as it works to launch this important therapy for patients in Europe.”
The marketing authorization will be held by Nycomed Danmark ApS** and is valid in the current EU Member States. National approvals are expected in Iceland and Norway within 30 days. It is based on data obtained from the STEPS pivotal Phase 3 safety and efficacy trial, a double blind, placebo controlled study in patients with SBS, who required parenteral nutrition. During the study, 43 patients were randomized to a subcutaneous 0.05 mg/kg/day dose of teduglutide and 43 patients to placebo for up to 24 weeks. 1
The proportion of patients treated with teduglutide who achieved a 20% to 100% reduction of parenteral nutrition at Week 20 and 24 was significantly higher compared with those receiving placebo, (63% versus 30%, p=0.002). Treatment with teduglutide resulted in a 4.4 litre/week reduction in parenteral nutrition requirements versus 2.3 litre/week for placebo at 24 weeks (p1
About Short Bowel Syndrome
Short bowel syndrome (SBS) is a highly disabling condition that can impair a patient's quality of life and lead to serious life-threatening complications. SBS typically arises after extensive resection of the bowel due to Crohn’s disease, ischemia or other conditions. SBS patients often suffer from malnutrition, severe diarrhoea, dehydration, fatigue, osteopenia, and weight loss due to the reduced intestinal capacity to absorb nutrients, water, and electrolytes. The usual treatment for short bowel syndrome is nutritional support, including parenteral nutrition (PN) and/or intravenous (IV) fluids to supplement and stabilize nutritional needs.
Although PN can provide nutritional support for short bowel syndrome patients, it does not improve the body’s own ability to absorb nutrients. PN is also associated with serious complications, such as infections, blood clots or liver damage, and the risks increase the longer patients are on PN. Patients on PN often experience a poor quality of life with difficulty sleeping, frequent urination and loss of independence.
About Teduglutide (Revestive®)
Teduglutide is a novel, recombinant analogue of human glucagon-like peptide 2 (GLP-2), a naturally occurring protein involved in the rehabilitation of the intestinal lining. It has been developed to reduce dependence on parenteral nutrition (PN) in adult patients with short bowel syndrome (SBS). Two Phase 3 studies of teduglutide demonstrated a favorable safety profile and significant reductions in mean PN volume from baseline to end of treatment. In addition some patients were able to be weaned off PN and continue their life without parenteral support. 1,2
Teduglutide has received orphan drug designation for the treatment of SBS from the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA).
In 2007, NPS Pharmaceuticals, Inc. (NASDAQ: NPSP), a specialty pharmaceutical company developing innovative therapeutics for rare gastrointestinal and endocrine disorders, granted Nycomed the rights to develop and commercialize teduglutide outside the United States, Canada and Mexico and Israel. NPS retains all rights to teduglutide in North America. NPS submitted a new drug application for teduglutide to the U.S. Food and Drug Administration (FDA) in November 2011. Teduglutide is known as Gattex® in the U.S.
References
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1. Publication of STEPS is in preparation. First results were report at the AGA 2011 in an abstract: Jeppesen PB, Pertkiewicz M, Seidner DL, O'Keefe S, Heinze H, Joelsson B: Teduglutide, a novel analogue of Glucagon-like Peptide 2 (GLP-2), is effective and safe in reducing parenteral support volume in short bowel syndrome–intestinal failure subjects: Results from a 24-week, placebo-controlled phase 3 trial (STEPS), Gastroenterology 2011; 140 (5), Supplement 1, S146
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2. Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O'Keefe SJ. Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut. 2011 Jul;60(7):902-14. Epub 2011 Feb 11.
About Takeda Pharmaceuticals Company Limited
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website,http://www.takeda.com.
About NPS Pharmaceuticals
NPS Pharmaceuticals is a biopharmaceutical company focused on bringing orphan products to patients with rare disorders and few, if any, therapeutic options. NPS is advancing two late-stage registration programs. A New Drug Application is undergoing FDA review for Gattex® (teduglutide) as a treatment for adult short bowel syndrome (SBS) and a Phase 3 registration study has been completed for Natpara™ (recombinant human parathyroid hormone (rhPTH [1-84]) in adult hypoparathyroidism. NPS’ earlier stage pipeline includes two calcilytic compounds, NPSP790 and NPSP795, with potential application in rare disorders involving increased calcium receptor activity, such as autosomal dominant hypocalcemia with hypercalciuria (ADHH). NPS complements its proprietary programs with a royalty-based portfolio of products and product candidates that includes agreements with Amgen, GlaxoSmithKline, Janssen Pharmaceuticals, Kyowa Hakko Kirin, and Nycomed (acquired by Takeda Pharmaceutical Company Limited). Additional information about NPS is available through its corporate website, http://www.npsp.com
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Forward-looking statements
This press release contains forward-looking statements. Forward-looking statements include statements regarding Takeda's and NPS' plans, outlook, strategies, results for the future, and other statements that are not descriptions of historical facts. Forward-looking statements may be identified by the use of forward-looking words such as "may," "believe," "will," "expect," "project," "estimate," "should," "anticipate," "plan," "assume," "continue," "seek," "pro forma," "potential," "target," "forecast," "guidance," "outlook" or "intend" or other similar words or expressions of the negative thereof. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors are cautioned not to unduly rely on such forward-looking statements.
Forward-looking statements involve risks and uncertainties that could cause actual results or experience to differ materially from that expressed or implied by the forward-looking statements. Some of these risks and uncertainties include, but are not limited to, (1) the economic circumstances surrounding Takeda's and NPS’ business, including general economic conditions in Japan, the United States and worldwide; (2) competitive pressures and developments; (3) applicable laws and regulations; (4) the success or failure of product development programs; (5) actions of regulatory authorities and the timing thereof; (6) changes in exchange rates; (7) claims or concerns regarding the safety or efficacy of marketed products or product candidates in development; and (8) integration activities with acquired companies.
The forward-looking statements contained in this press release speak only as of the date of this press release, and Takeda and NPS undertake no obligation to revise or update any forward-looking statements to reflect new information, future events or circumstances after the date of the forward-looking statement. If Takeda and NPS do update or correct one or more of these statements, investors and others should not conclude that Takeda will make additional updates or corrections.
Information
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).
