New Drug Approvals

Home » NEW DRUGS » TEDIGLUTIDE ..Glucagon-like peptide 2 (GLP-2) analog; protects small intestinal stem cells from radiation damage.

TEDIGLUTIDE ..Glucagon-like peptide 2 (GLP-2) analog; protects small intestinal stem cells from radiation damage.

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

PAYPAL DONATIONS

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Categories

Blog Stats

  • 1,563,567 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,943 other followers

add to any

Share

File:Teduglutide.png

TEDUGLUTIDE
Glucagon-like peptide 2 (GLP-2) analog; protects small intestinal stem cells from radiation damage.

Gattex (teduglutide) is a recombinant analog of human glucagon-like peptide 2 for the treatment of adults with short bowel syndrome.

  • (Gly2)GLP-2
  • ALX 0600
  • ALX-0600
  • Gattex
  • Gly(2)-GLP-2
  • Teduglutide
  • UNII-7M19191IKG

[Gly2]hGLP-2, [Gly2]-hGLP-2, ALX-0600,

Gattex, Revestive

CAS number 197922-42-2

L-histidylglycyl-L-α-aspartylglycyl-L-seryl-L-phenylalanyl-L-seryl-L-α-aspartyl-L-α-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-α-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-α-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid

Formula C164H252N44O55S 
Mol. mass 3752.082 g/mol

Gattex, ALX-0600, (Gly2)GLP-2, Gly(2)-GLP-2, ALX 0600, [Gly2]GLP-2, Glucagon-like peptide II (2-glycine) (human), UNII-7M19191IKG

LAUNCHED 2013, NPS Pharmaceuticals

APPROVAL FDA

Company: NPS Pharmaceuticals, Inc.
Date of Approval: December 21, 2012 FDA

NDA 203441

POWDER; SUBCUTANEOUS GATTEX

U-1320=TREATMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME WHO ARE DEPENDENT ON PARENTERAL SUPPORT

Patent No Patent Expiry Date Patent use code
5789379 Apr 14, 2015 U-1320
7056886 Sep 18, 2022 U-1320
7847061 Nov 1, 2025 U-1320
Exclusivity Code Exclusivity_Date
ORPHAN DRUG EXCLUSIVITY Dec 21, 2019
NEW CHEMICAL ENTITY Dec 21, 2017

SEE FDA

http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203441Orig1s000lbl.pdf

CLINICAL TRIALS

http://clinicaltrials.gov/search/intervention=Teduglutide+OR+ALX-0600

The active ingredient in GATTEX (teduglutide [rDNA origin]) for injection is teduglutide (rDNA origin), which is a 33 amino acid glucagon-like peptide-2 (GLP-2) analog manufactured using a strain of Escherichia coli modified byrecombinant DNA technology. The chemical name of teduglutide is L-histidyl-L-glycyl-L-aspartyl-L-glycyl-L-seryl-L-phenylalanyl-L-seryl-L-aspartyl-L-glutamyl-L-methionyl-L-asparaginyl-L-threonyl-L-isoleucyl-L-leucyl-L-aspartyl-L-asparaginyl-L-leucyl-L-alanyl-L-alanyl-L-arginyl-L-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparaginyl-L-tryptophanyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid. The structural formula is:

Figure 1: Structural formula of teduglutide

GATTEX (teduglutide) structural formula illustration

Teduglutide has a molecular weight of 3752 Daltons. Teduglutide drug substance is a clear, colorless to light-straw–colored liquid.

Each single-use vial of GATTEX contains 5 mg of teduglutide as a white lyophilized powder for solution for subcutaneous injection. In addition to the active pharmaceutical ingredient (teduglutide), each vial of GATTEX contains 3.88 mg L-histidine, 15 mg mannitol, 0.644 mg monobasic sodium phosphate monohydrate, 3.434 mg dibasic sodium phosphate heptahydrate as excipients. No preservatives are present.

At the time of administration the lyophilized powder is reconstituted with 0.5 mL of Sterile Water for Injection, which is provided in a prefilled syringe. A 10 mg/mL sterile solution is obtained after reconstitution. Up to 0.38 mL of the reconstituted solution which contains 3.8 mg of teduglutide can be withdrawn for subcutaneous injection upon reconstitution.

Teduglutide (brand names Gattex and Revestive) is a 36-membered polypeptide andglucagon-like peptide-2 analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion.[1] In Europe it is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on December 21, 2012.

Teduglutide is a proprietary analogue of glucagon-like peptide 2 (GLP-2) which was approved in the U.S. in December 2012 for the once-daily treatment of short-bowel syndrome in adults who are dependent on parenteral support. Commercial launch took place in 2013.The product was filed for approval in the E.U. in 2011 by Nycomed for this indication. In June 2012, a positive opinion was received in the E.U. and final approval was assigned in September 2012.

At NPS Pharmaceuticals, the compound is in phase III clinical development for this indication in pediatric patients and in phase II clinical studies for the treatment of Crohn’s disease. Preclinical studies are also ongoing at the company for the treatment of chemotherapy-induced enterocolitis and for the prevention and treatment of necrotizing enterocolitis (NEC) in preterm infants.

Teduglutide has been found to induce intestinal hyperplasia, reduce apoptosis and inflammation and improve cell barrier integrity in animal models. In 2001, orphan drug designation was assigned to teduglutide for the treatment of short-bowel syndrome.

In 2007, the compound was licensed to Nycomed for development and commercialization outside the U.S., Canada and Mexico for the treatment of gastrointestinal disorders. In 2012, the product was licensed to Neopharm by NPS Pharmaceuticals in Israel for development and commercialization for the treatment of gastrointestinal disorders.

The estimated prevalence of short bowel syndrome (SBS) patients with non-malignant disease requiring home parenteral nutrition (HPN) is at least 40 per million of the U.S. population. SBS usually results from surgical resection of some or most of the small intestine for conditions such as Crohn’s disease, mesenteric infarction, volvulus, trauma, congenital anomalies, and multiple strictures due to adhesions or radiation. Surgical resection may also include resection of all or part of the colon. SBS patients suffer from malabsorption that may lead to malnutrition, dehydration and weight loss. Some patients can maintain their protein and energy balance through hyperphagia; more rarely they can sustain fluid and electrolyte requirements to become independent from parenteral fluid.

Although long-term parenteral nutrition (PN) is life saving in patients with intestinal failure, it is expensive, impairs quality of life and is associated with serious complications such as catheter sepsis, venous occlusions and liver failure. Treatments that amplify absolute intestinal absorption, and eliminate or minimize the need for PN have great potential significance to SBS patients.

The endogenous meal-stimulated hormone, glucagon-like peptide-2 (GLP-2), raises considerable interest for SBS patients. GLP-2 functions to slow gastric emptying, reduce gastric secretions, increase intestinal blood-flow and stimulate growth of the small and large intestine. In animal studies, GLP-2 administration induces mucosal epithelial proliferation in the stomach and small and large intestine by stimulation of crypt cell proliferation and inhibition of enterocyte apoptosis.

SBS patients with end-jejunostomy and no colon have low basal GLP-2 levels and limited meal-stimulated GLP-2 secretion due to removal of GLP-2 secreting L-cells, which are located primarily in the terminal ileum and colon. This GLP-2 deficiency results in a minimal adaptive response following resection and could explain the gastric hypersecretion, rapid intestinal transit and lack of intestinal adaptation observed in these SBS patients.

Jeppesen et al. (Gastroenterology 2001; 120:806-815) have described positive benefit in an open-label study using pharmacologic doses of native GLP-2 in SBS jejunostomy patients. There was significant improvement in intestinal wet weight absorption and a more modest improvement in energy absorption that led to an increase in body weight, lean body mass and a rise in urinary creatinine excretion.

In contrast, SBS patients with colon-in-continuity have elevated basal endogenous GLP-2 levels resulting in an adaptive response to resection characterized by improved wet weight gain and energy absorption. The potential for added benefit of pharmacologic doses of GLP-2 receptor agonists in these patients is not obvious and has not been studied.

TEDUGLUTIDE

  1.  Jeppesen PB (May 2012). “Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome”Therap Adv Gastroenterol 5 (3): 159–71. doi:10.1177/1756283X11436318PMC 3342570PMID 22570676.
  2. US 2013157954
  3. WO 2006050244
  4. WO 2005021022
  5. US 6586399
  6. WO 2002066062
  7. US 6297214
  8. US 2001021767
  9. WO 2001041779
  10. WO 1999058144
  11. WO 1998052600

Gattex Approved By FDA For Short Bowel Syndrome

Gattex (teduglutide) has been approved by the U.S. Food and Drug Administration to be used in patients that have short bowel syndrome and require parenteral nutrition.

The drug, once it is in the market, will compete against two others that have been approved by the FDA for this type of patient population. Those two medications are Nutrestore (glutamine) and Zorbtive (Somatropin).

Short bowel syndrome comes on following the removal surgically of part of the large or small intestine or part of both. Patients who are affected must have parenteral nutrition due to the poor absorption they have of nutrients and fluids. Teduglutide is injected one time each day and improves the absorption making it less important to have nutrition assistance.

The advisory committee for the FDA voted unanimously in October to recommend the drug’s approval after seeing the results from a pair of clinical trials that showed the advantage teduglutide had over just a placebo in at least a reduction of 20% in the amount of parenteral nutrition at 6 months.

During the first clinical trial, 46% of the patients that took the drug saw a level of reduction, which was compared to only 6% who had taken only a placebo. In the other study, the figure increased to 63%, while the placebo rated was up to 30%

The side effects most common found in those who use teduglutide during the trials included nausea, reactions around the injection site, abdominal pain abdominal distension and headaches.

………..

US5789379 Jun 28, 1996 Aug 4, 1998 1149336 Ontario Inc. Glucagon-like peptide-2 analogs
US6077949 Apr 24, 1997 Jun 20, 2000 Allelix Biopharmaceuticals, Inc. Cloned glucagon-like peptide 2 receptors
US6184201 * Apr 8, 1997 Feb 6, 2001 Nps Allelix Corp. Intestinotrophic glucagon-like peptide-2 analogs
US7411039 Oct 14, 2003 Aug 12, 2008 Novo Nordisk A/S GLP-2 compounds, formulations, and uses thereof
EP1231219A1 Apr 11, 1997 Aug 14, 2002 1149336 Ontario Inc. GLucagon-like peptide-2 analogs
WO1997039031A1 Apr 11, 1997 Oct 23, 1997 Allelix Biopharma Glucagon-like peptide-2 analogs
WO1997039091A1 Apr 16, 1997 Oct 23, 1997 Burckett St Laurent James Char Mid-chain branched surfactants
WO2002066511A2 Feb 15, 2002 Aug 29, 2002 Conjuchem Inc Long lasting glucagon-like peptide 2 (glp-2) for the treatment of gastrointestinal diseases and disorders

 

 

ANTHONY MELVIN CRASTO

THANKS AND REGARD’S
DR ANTHONY MELVIN CRASTO Ph.D

GLENMARK SCIENTIST , NAVIMUMBAI, INDIA

did you feel happy, a head to toe paralysed man’s soul in action for you round the clock

need help, email or call me

MOBILE-+91 9323115463
web link

I was  paralysed in dec2007, Posts dedicated to my family, my organisation Glenmark, Your readership keeps me going and brings smiles to my family

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Paypal Donate

DR ANTHONY CRASTO

Follow New Drug Approvals on WordPress.com

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,943 other followers

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 29 year tenure till date Aug 2016, Around 30 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

Personal Links

View Full Profile →

TWITTER

Error: Twitter did not respond. Please wait a few minutes and refresh this page.

bloglovin

Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: