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Plus the 14 other new drugs marketed in 2010.
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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Synthetic approaches to the 2010 new drugs-Review Article Bioorganic & Medicinal Chemistry, Vol 20, Issue 3,2012, Pg 1155-1174
| Synthetic approaches to the 2010 new drugsReview Article Bioorganic & Medicinal Chemistry, Volume 20, Issue 3, 1 February 2012, Pages 1155-1174 Kevin K.-C. Liu, Subas M. Sakya, Christopher J. O’Donnell, Andrew C. Flick, Hong X. Ding |
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Miglustat- to treat Type 1 Gaucher disease (GD1)
 |
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|---|---|
| Miglustat | |
| (2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol |
PATENT-US 5,525,616, US 5,472,969 TO Actelion Pharms Ltd
Miglustat is a drug developed by Actelion and is used primarily to treat Type 1 Gaucher disease (GD1). It is marketed under the trade name Zavesca. Miglustat (OGT 918, N-butyl-deoxynojirimycin) is an imino sugar (molecular weight: 219 daltons), a synthetic analogue of D-glucose and a white to off-white crystalline solid that has a bitter taste The primary pharmacological activity of miglustat is inhibition of the enzyme glucosylceramide synthase, catalyzing the first step in the biosynthesis of glycosphingolipids (GSL), i.e., the formation of glucosylceramide (GlcCer). Reduced formation of GlcCer will lead to decreased biosynthesis of more complex GSL. This therapeutic principle, called substrate reduction therapy (SRT), may be useful in disorders of intracellular (predominantly lysosomal) accumulation of GSL either due to their deficient breakdown or intracellular transport/trafficking. Miglustat exhibits a large volume of distribution and has the capacity to access deep organs such as the brain, bone and lung.
Miglustat is a synthetic derivative of a family of polyhydroxylated alkaloids or amino sugar extracted from plants and microorganisms. Its synthesis starts from D-glucose sugar in plants. The sugar then aminated and oxidized to amino fructose sugar, which then can form a cyclic aminohemiacetal called nojirimycin. Then the dehydration and reduction takes place successively before the formation of deoxynojirimycin, which is a precursor of miglustat. Since it is a synthetic derivative drug, alkylation ofdeoxynojirimycin can be synthesized in the laboratory with 1-butyl halide via amine alkylation.
Miglustat
CAS : 72599-27-0
(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)-3,4,5-piperidinetriol
Additional Names: N-butyldeoxynojirimycin; N-butylmoranoline
Manufacturers’ Codes: OGT-918; SC-48334
Trademarks: Zavesca (Actelion)
Molecular Formula: C10H21NO4
Molecular Weight: 219.28
C 54.77%, H 9.65%, N 6.39%, O 29.19%
Literature Ref: Amino sugar; inhibitor of glucosyltransferase, an enzyme involved in the biosynthesis of glycosphingolipids.
Prepn: B. Junge et al., DE 2758025; see also, eidem, US 4639436 (1979, 1987 both to Bayer).
Improved synthesis: E. W. Baxter, A. B. Reitz, J. Org. Chem. 59, 3175 (1994); C. R. R. Matos et al., Synthesis 1999, 571.
In vitro efficacy vs HIV: A. Karpas et al., Proc. Natl. Acad. Sci. USA 85, 9229 (1988). Inhibition of glycolipid biosynthesis: F. M. Platt et al., J. Biol. Chem. 269, 8362 (1994).
Clinical evaluation in Gaucher’s disease: T. Cox et al., Lancet 355, 1481 (2000). Review of pharmacology and clinical development in Gaucher’s disease: P. L. McCormack, K. L. Goa, Drugs 63, 2427-2434 (2003).
Properties: White to off-white crystalline solid, mp 125-126°. [a]D25 -15.9° (c = 0.77 in water). Highly sol in water (>1000 mg/ml).
Melting point: mp 125-126°
Optical Rotation: [a]D25 -15.9° (c = 0.77 in water)
Therap-Cat: In treatment of inherited glycosphingolipid lysosomal storage disorders.
by
WORLD DRUG TRACKER
AstraZeneca buys Pearl Therapeutics in $1.15bn deal
The UK’s second largest drug company, AstraZeneca, has announced that it will buy US-based lung disease drug specialist Pearl Therapeutics in a deal worth up to $1.15bn (£742m).
read all at
A positive genotoxicity result can throw the fate of a promising drug candidate—in which a firm has invested significant time and money—into doubt
A positive genotoxicity result can throw the fate of a promising drug candidate-in which a firm has invested significant time and money-into doubt. The statistical improbability and challenges of bringing a drug to market become paramount.
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BY WORLD DRUG TRACKER
Otsuka Pharmaceutical Submits New Drug Application in Japan for Tolvaptan for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
TOLVAPTAN
may 30 2013
- Tolvaptan was discovered by Otsuka in Japan, and its primary results from a global clinical trial involving 1,400 ADPKD patients from 15 countries, which demonstrated a statistically significant reduction in the rate of total kidney volume, were published in New England Journal of Medicine in 2012. It is also currently under a fast track review in the US, following our announcement of FDA accepting to review the application in April 2013.
- ADPKD is a hereditary and often physically and mentally burdensome disease characterized by the development of multiple cysts in the kidneys. ADPKD is often associated with pain, hypertension, decreased kidney function and ultimately, kidney failure that may result in hemodialysis or kidney transplantation.
- There are estimated to be approximately 31,000 ADPKD patients in Japan, and the diagnosed prevalence is estimated to be between 1:1000 and 1:4000 globally.
(Tokyo, Japan, May 30, 2013) – Otsuka Pharmaceutical Co., Ltd. Today announced it filed an application with the Pharmaceutical and Medical Devices Agency in Japan (PMDA) to market its novel compound tolvaptan for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Phase III clinical trial results that form the basis of the regulatory filing were published in the New England Journal of Medicine in November 2012. The MHLW has designated tolvaptan as an Orphan Drug.http://www.otsuka.co.jp/en/release/2013/0603_02.html
Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated withcongestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone(SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolvat & Tolsama.
Tolvaptan is also in fast-track clinical trials[2] for polycystic kidney disease. In a 2004 trial, tolvaptan, when administered with traditional diuretics, was noted to increase excretion of excess fluids and improve blood sodium levels in patients with heart failure without producing side effects such as hypotension (low blood pressure) or hypokalemia(decreased blood levels of potassium) and without having an adverse effect on kidney function.[3] In a recently published trial (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948) the study met its primary and secondary end points. Tolvaptan, when given at an average dose of 95 mg per day over a 3-year period, slowed the usual increase in kidney volume by 50% compared to placebo (2.80% per year versus 5.51% per year, respectively, p<0.001) and reduced the decline in kidney function when compared with that of placebo-treated patients by approximately 30% (reciprocal serum creatinine, -2.61 versus -3.81 (mg/mL)-1 per year, p <0.001)[4]
Chemical synthesis:[5] 
- Shoaf S, Elizari M, Wang Z, et al. (2005). “Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias”. J Cardiovasc Pharmacol Ther 10 (3): 165–71. doi:10.1177/107424840501000304. PMID 16211205.
- Otsuka Maryland Research Institute, Inc.
- Gheorghiade M, Gattis W, O’Connor C, et al. (2004). “Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial”. JAMA 291 (16): 1963–71. doi:10.1001/jama.291.16.1963. PMID 15113814.
- (2012) Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
- Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.
- http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm?source=govdelivery
- Gheorghiade M, Niazi I, Ouyang J et al. (2003). “Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial”. Circulation 107 (21): 2690–6. doi:10.1161/01.CIR.0000070422.41439.04.PMID 12742979.
FDA panel urges looser restrictions on diabetes drug Avandia
june 6 2013,
The controversial diabetes drug Avandia will get a second look from federal regulators this week, nearly two years after its use was severely restricted because of a link to heart problems.
The U.S. Food and Drug Administration has convened a panel of experts to consider an independent review by Duke University researchers of Avandia’s original clinical trial. The expert panel will conclude its sessions on Thursday, and could decide to alter or even lift the tight restrictions now in place regarding the medication’s use.
The Duke scientists did uncover some previously unreported cases of heart complications and deaths, but concluded that these cases did not significantly raise the overall risk of heart disease and the conclusions of the original trial still hold.
The FDA’s reconsideration of Avandia’s safety has prompted stinging criticism from the drug’s detractors, who say the agency is trying to save face following a very public embarrassment over the drug.
“This is a drug that has essentially been off the market in almost the entire world for the last three years. It has been banned in most countries, and is available in the United States under such strict requirements that only 3,000 patients now take it,” said Dr. Steven Nissen, the Cleveland Clinic cardiologist who first led the charge against Avandia. “It’s really about the FDA wanting to clean up its image, not about whether the drug is actually safe or unsafe.”
The FDA has defended its decision to review the Duke re-analysis of the original trial, which was conducted by the drug’s maker, GlaxoSmithKline, under the name Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD).
“Given the public interest in Avandia, the extensive history of the product and the continued uncertainty of risk, the FDA is holding the advisory committee meeting to have a transparent, public discussion of the results of the RECORD readjudication,” FDA spokesperson Morgan Liscinsky said.
Avandia quickly became a blockbuster diabetes drug following its release in 1999, with sales topping $3 billion in 2006.
Eisai Announces Availability of BELVIQ® (lorcaserin HCl) CIV Tablets for Chronic Weight Management in Adults who are Overweight with a Comorbidity or Obese BELVIQ Available in U.S. Pharmacies within One Week
LORCASERIN
june 7, 2013 –Eisai Inc. announced today that BELVIQ (pronounced BEL-VEEK) will be available to eligible patients by prescription in the United States beginning June 11.
BELVIQ was approved by the U.S. Food and Drug Administration on June 27, 2012 to be used along with a reduced-calorie diet and increased physical activity for chronic weight management in adults who have a body mass index (BMI) of 30 kg/m2 or greater (obese), or BMI of 27 kg/m2 or greater (overweight) with at least one weight-related medical condition such as high blood pressure, high cholesterol, or type 2 diabetes. It is not known if BELVIQ is safe and effective when taken with other prescription, over-the-counter, or herbal weight loss products, nor is it known if BELVIQ changes your risk of heart problems or stroke, or of death due to heart problems or stroke.
“BELVIQ is a new treatment option for the medical management of patients who are obese and who have not been able to sustain long-term weight loss by altering their diets or increasing exercise alone,” said Lonnel Coats, President and Chief Executive Officer, Eisai Inc. “Eisai is committed to making BELVIQ available to appropriate patients as part of our human health care corporate mission of keeping patients’ medical needs at the forefront of all that we do.”
BELVIQ will be available in U.S. pharmacies only with a prescription. Patients are cautioned not to buy BELVIQ from parties offering BELVIQ without a valid prescription from their doctor. Eisai will market and distribute BELVIQ in the United States and Arena Pharmaceuticals will manufacture and supply the finished commercial product from its facility in Switzerland.
“BELVIQ provides appropriate patients with a new treatment option that along with diet and exercise can help them lose weight and keep the weight off,” said Ken Fujioka, M.D., Director of the Center for Weight Management at the Scripps Clinic. “Obesity needs to be recognized and treated as a chronic disease. The availability of BELVIQ is a significant milestone in the medical management of overweight and obesity as we work to slow this epidemic in the United States.”
Lorcaserin (APD-356, trade name upon approval Belviq,expected trade name during development, Lorqess) is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic. On 22 December 2009 a New Drug Application (NDA) was submitted to the Food and Drug Administration (FDA) in the United States.On 16 September 2010, an FDA advisory panel voted to recommend against approval of the drug based on concerns over both safety and efficacy. In October 2010, the FDA stated that it could not approve the application for lorcaserin in its present form.
On 10 May 2012, after a new round of studies submitted by Arena, an FDA panel voted to recommend lorcaserin with certain restrictions and patient monitoring. The restrictions include patients with a BMI of over 30, or with a BMI over 27 and a comorbidity like high blood pressure or type 2 diabetes.
On 27 June 2012, the FDA officially approved lorcaserin for use in the treatment of obesity for adults with a BMI equal to or greater than 30 or adults with a BMI of 27 or greater who “have at least one weight-related health condition, such as high blood pressure, type 2 diabetes, or high cholesterol”.
On 07 May 2013, the US Drug Enforcement Administration has classified lorcaserin as a Schedule IV drug[10] under the Controlled Substances Act.
About BELVIQ (lorcaserin HCl) CIV Tablets
BELVIQ is believed to decrease food consumption and promote satiety by selectively activating serotonin 2C receptors in the brain. The exact mechanism of action of BELVIQ is not known. BELVIQ is a federally controlled substance (CIV) because it may be abused or lead to drug dependence. For more information about BELVIQ,
sNDA – FDA accepts AMAG Feraheme (Ferumoxytol) sNDA for review
Feraheme (ferumoxytol)
Iron(II,III) oxide
Fe3O4
CUT PASTE OF INFO….
7 MAR 2013
The US Food and Drug Administration (FDA) has accepted for review AMAG Pharmaceuticals’ supplemental new drug application (sNDA) for Feraheme (ferumoxytol) injection for Intravenous (IV) use.
The sNDA filed is to expand the indication for ferumoxytol for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney disease (CKD), who have failed or could not take oral iron treatment.
Ferumoxytol is currently indicated for oral use for the treatment of IDA in adult patients with CKD, according to the company.
The sNDA included the data from a global phase III program, which included two phase III clinical trials such as as IDA-301 (placebo comparator) and IDA-302 (active comparator).
The trials, which enrolled 1,400 patients, evaluated the use of ferumoxytol in a broad range of adult IDA patients, all of whom had failed or could not take oral iron treatment.
Both studies achieved the primary efficacy endpoints with statistically significant improvements in hemoglobin from baseline to the 35-day.
The studies, which also included patient-reported outcomes data as pre-specified secondary and exploratory endpoints, found no new safety signals, outside of those described in the current Feraheme (ferumoxytol) label, were observed with ferumoxytol treatment in these studies, claims the company.
In response to the application, the FDA said it will complete the review of Feraheme sNDA by 21 October 2013.
Feraheme, an iron replacement product, is a non-stoichiometric magnetite (superparamagnetic iron oxide) coated with polyglucose sorbitol carboxymethylether. The overall colloidal particle size is 17-31 nm in diameter. The chemical formula of Feraheme is Fe5874O8752-C11719H18682O9933Na414 with an apparent molecular weight of 750 kDa.
Feraheme injection is an aqueous colloidal product that is formulated with mannitol. It is a black to reddish brown liquid, and is provided in single use vials containing 510 mg of elemental iron. Each mL of the sterile colloidal solution of Feraheme injection contains 30 mg of elemental iron and 44 mg of mannitol, and has low bleomycin-detectable iron. The formulation is isotonic with an osmolality of 270-330 mOsm/kg. The product contains no preservatives, and has a pH of 6 to 8.
Ferumoxytol
STRUCTURE SOURCE http://chem.sis.nlm.nih.gov/chemidplus/rn/1309-38-2
Molecular Formulas
-
Fe.O
-
Fe3-O4
Molecular Weight
- 231.531
Ferumoxytol [USAN]
RN: 1309-38-2
Polyglucose sorbitol carboxymethyl ether-coated non-stoichiometric magnetite. Ferumoxytol is a superparamagnetic iron oxide that is coated with a low molecular weight semi-synthetic carbohydrate, polyglucose sorbitol carboxymethyl ether. The iron oxide is a superparamagnetic form of non-stoichiometric magnetite with crystal size of 6.2 to 7.3 nm. In solution, the colloidal particle of ferumoxytol has a Stokes diameter of 18-20 nm. Molecular weight is approximately 308,000
Iron oxide (Fe3O4). It is a black ore of IRON that forms opaque crystals and exerts strong magnetism. The NANOPARTICLES; and MICROSPHERES of its mineral form, magnetite, have many biomedical applications.
Ferumoxytol is the generic ingredient in one branded drug marketed by Amag Pharms Inc and is included in one NDA. There are six patents protecting this compound and one Paragraph IV challenge. Additional information is available in the individual branded drug profile pages.
This ingredient has eleven patent family members in ten countries.
There is one drug master file entry for ferumoxytol. One supplier is listed for this compound.
Phase II
Cas 722492-56-0
Launched – 2009, Anemia, iron deficiency
7228
AMI-7228
Code-7228
A superparamagnetic iron oxide (non-stoichiometric magnetite) coated with a low molecular weight semi-synthetic carbohydrate polyglucose carboxymethyl ether; USAN (OO-74) (Advanced Magnetics, Cambridge, MA, USA)
Other Names
- C 7228
- Code 7228
- Cytogen
- Feraheme
- Rienso
Superparamagnetic iron oxide coated with a low molecular weight semi-synthetic carbohydrate polyglucose sorbitol carboxymethyl ether. The iron oxide is a superparamagnetic form of non-stoichiometric magnetite with crystal size of 6.2 to 7.3 nm. In solution, the colloidal particle has a Stokes diameter of 18-20 nm
CLICK ON IMAGE
CLICK O IMAGE
Feraheme, an iron replacement product, is a non-stoichiometric magnetite (superparamagnetic iron oxide) coated with polyglucose sorbitol carboxymethylether. The overall colloidal particle size is 17-31 nm in diameter. The chemical formula of Feraheme is Fe5874O8752C11719H18682O9933Na414 with an apparent molecular weight of 750 kDa.
Feraheme Injection is an aqueous colloidal product that is formulated with mannitol. It is a black to reddish brown liquid, and is provided in single use vials containing 510 mg of elemental iron. Each mL of the sterile colloidal solution of Feraheme Injection contains 30 mg of elemental iron and 44 mg of mannitol, and has low bleomycin-detectable iron. The formulation is isotonic with an osmolality of 270-330 mOsm/kg. The product contains no preservatives, and has a pH of 6 to 8.
Ferumoxytol is AMAG Pharmaceuticals’ lead investigational compound. In 2007, the company filed a regulatory application seeking approval in the U.S. for use as an intravenous iron replacement therapeutic in patients who may be on dialysis and are suffering from anemic chronic kidney disease (CKD). In 2009, FDA approval was assigned and the product became available on the market. A regulatory application was filed in the E.U. in 2010 for this indication and a positive opinion was received in 2012. Final E.U. approval was obtained in June 2012. In 2012, AMAG Pharmaceuticals submitted a supplemental NDA to the FDA for the treatment of patients with iron-deficiency anemia (IDA) who are not candidates for oral iron, for which they received a complete response letter in January 2014. In 2013, Takeda filed for approval for this indication in the E.U. This application was withdrawn in 2015 due to safety concerns.
In terms of clinical studies, phase II trials are underway at AMAG and at Oregon Health and Science University for use in magnetic resonance angiography (MRA). The National Cancer Institute is also conducting phase II trials for the imaging of primary high-grade brain tumors and/or cerebral metastases from lung or breast cancer. Phase I clinical trials are ongoing at Dana-Farber Cancer Institute for use in magnetic resonance imaging in pediatric and adult patients with malignant sarcoma.
The drug consists of intravenously administered bioavailable iron which allows for more efficient replenishment of the body’s iron stores than oral iron supplements, without their associated common side effects. Ferumoxytol is a blood pool agent, a true intravascular contrast agent that remains in the blood stream for an extended period of time. Based on this quality, the product may be useful as a contrast agent in a wide range of applications in MRI.
In 2008, fast track designation was received in the U.S. as a diagnostic agent for vascular-enhanced magnetic resonance imaging (VE-MRI) to improve the assessment of peripheral arterial disease in patients with known or suspected chronic kidney disease. In 2010, a license, development and commercialization agreement was established between Takeda and AMAG Pharmaceuticals in Asia Pacific countries (excluding Japan, China and Taiwan), Canada, Europe, the Commonwealth of Independent States and Turkey. However, in December 2014, both companies announced the termination of this license agreement. In 2011, orphan drug designation was assigned by the FDA for use in magnetic resonance imaging in brain metastases. This designation was assigned in 2012 for use in magnetic resonance imaging to assess, and monitor treatment of solid tumor malignancies previously diagnosed in pediatric patients (age 16 years and younger).
SFDA
As announced in May 2008, we entered into a development and commercialization agreement with AMAG Pharmaceuticals, Inc. (“AMAG”) (NASDAQ:AMAG), a US biopharmaceutical company, for ferumoxytol, an intravenous iron replacement therapeutic agent being developed to treat iron deficiency anemia in CKD patients and in patients requiring hemodialysis.
Under the terms of the agreement, AMAG granted us exclusive rights to develop and commercialize ferumoxytol in the PRC, initially for CKD, and with an option to expand into additional indications. We will be responsible for the clinical development, registration, and commercialization of ferumoxytol in the PRC. We and AMAG will form a joint steering committee, with equal representation from both parties, to oversee and guide the development and commercialization of ferumoxytol in China. The agreement has an initial duration of 13 years and will be automatically renewed for a set term if minimum sales thresholds are achieved. AMAG will retain all manufacturing rights for ferumoxytol and will provide, under a separate agreement, commercial supply to us at a predetermined supply price.
Ferumoxytol was approved in June 2009 by the U.S. Food and Drug Administration to treat iron deficiency anemia in CKD patients and launched commercially in the U.S. by AMAG in July 2009. Ferumoxytol received marketing approval in Canada in December 2011 and a positive recommendation for approval from the Committee for Medicinal Products for Human Use of the European Medicines Agency in April 2012.
We have submitted the application for a registrational clinical trial for ferumoxytol to SFDA, as announced in January 2010. Once approved by the SFDA, we will commence a multi-center randomized efficacy and safety study in China with approximately 200 CKD patients, measuring the mean change in hemoglobin from baseline at Day 35 after first dose.
https://www.google.com/patents/US20100266644
Ferumoxytol is a newer parenteral iron formulation but limited information is available as to its efficacy and administration. See e.g., Landry et al. (2005) Am J Nephrol 25, 400-410, 408; and Spinowitz et al. (2005) Kidney Intl 68, 1801-1807; U.S. Pat. No. 6,599,498.
Another example of a preferred iron carbohydrate complex for use in the methods described herein is a carboxyalkylated reduced polysaccharide iron oxide complex (e.g., ferumoxytol, described in U.S. Pat. No. 6,599,498).
Another preferred iron carbohydrate complex for use in the methods described herein is a polyglucose sorbitol carboxymethyl ether-coated non-stoichiometric magnetite (e.g., “ferumoxytol”). Ferumoxytol is known in the art to be effective for treating anemia (at single unit doses lower than described herein). See e.g., Spinowitz et al. (2005) Kidney Intl 68, 1801-1807. Ferumoxytol is a superparamagnetic iron oxide that is coated with a low molecular weight semi-synthetic carbohydrate, polyglucose sorbitol carboxymethyl ether. Ferumoxytol and its synthesis are described in U.S. Pat. No. 6,599,498, incorporated herein by reference. Safety, efficacy, and pharmacokinetics of ferumoxytol are as described, for example, in Landry et al. (2005) Am J Nephrol 25, 400-410, 408; and Spinowitz et al. (2005) Kidney Intl 68, 1801-1807.
The iron oxide of ferumoxytol is a superparamagnetic form of non-stoichiometric magnetite with a crystal size of 6.2 to 7.3 nm. Average colloidal particle size can be about 30 nm, as determined by light scattering. Molecular weight is approximately 750 kD. The osmolarity of ferumoxytol is isotonic at 297 mOsm/kg and the pH is neutral. The blood half-life of ferumoxytol is approximately 10-14 hours. It has been previously reported that ferumoxytol can be given by direct intravenous push over 1-5 minutes in doses up to 1,800 mg elemental iron per minute, with maximal total dose up to 420 mg per injection. Landry et al. (2005) Am J Nephrol 25, 400-410, 408.
About Feraheme® (ferumoxytol)/Rienso
In the United States, Feraheme (ferumoxytol) Injection for Intravenous (IV) use is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have failed oral iron therapy. Feraheme received marketing approval from the FDA on June 30, 2009 for the treatment of IDA in adult chronic kidney disease (CKD) patients and was commercially launched by AMAG in the U.S. shortly thereafter.
Ferumoxytol is protected in the U.S. by five issued patents covering the composition and dosage form of the product. Each issued patent is listed in the FDA’s Orange Book. These patents are set to expire in March 2020; a request for patent term extension has been filed, which, if granted, may extend the patent term to June 2023 for one of the patents.
Ferumoxytol received marketing approval in Canada in December 2011, where it is marketed by Takeda as Feraheme, and in the European Union in June 2012 and Switzerland in August 2012, where it is marketed by Takeda as Rienso.
For additional U.S. product information, including full prescribing information, please visit www.feraheme.com.
AMAG now has five Orange Book-listed patents for ferumoxytol, with patent protection through March 2020, without patent term extension. AMAG has applied for a patent term extension for an Orange Book-listed ferumoxytol patent, which would lengthen that patent term through June 2023.
//////////Ferumoxytol, AMAG Pharmaceuticals, Phase II, 722492-56-0, Launched, 2009, Anemia, iron deficiency, 7228 , AMI-7228 , Code-7228
[Fe](O[Fe]=O)O[Fe]=O
NDA FDA-Nuvo reports FDA response to PENNSAID 2% , diclofenac sodium topical solution, 2% w/w
DICLOFENAC
PENNSAID 2%
7 MAR 2013
The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Nuvo Research’s US licensing partner, Mallinckrodt, following the review of Mallinckrodt’s New Drug Application (NDA) for diclofenac sodium topical solution, 2% w/w (PENNSAID 2%).
FDA in the letter mentioned that it requires Mallinckrodt’s complete pharmacokinetic study comparing PENNSAID 2% to original PENNSAID 1.5%.
FDA denied to review the similar pharmacokinetic studies submitted by Mallinckrodt with the NDA, as the reserve samples were not retained at the clinical site.
Pharmacokinetic studies are standard studies conducted during a drug development program to identify the total exposure or the amount of drug that reaches the blood stream after a patient receives both single and multiple doses of the product.
Mallinckrodt has suggested Nuvo that it expects to complete the study and submit the results to the FDA in the third quarter of 2013, and that it anticipates the FDA will provide a formal response to the filing within 6 months thereafter.
Nuvo’s Pain Group president Dr. Bradley Galer said with the new FDA’s letter the firm was disappointed that PENNSAID 2% will not be approved in this review cycle.
“We are pleased that the FDA has outlined a clear pathway to approval that we believe can be completed in a relatively short time frame,” Galer added.
“Upon approval, PENNSAID 2% will be the first and only topical NSAID in the U.S. featuring twice per day dosing and a metered dose pump bottle.”
New Drug Approvals 