DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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TONIX Completes Pre-Phase 3 Meeting With U.S. Food and Drug Administration for TNX-102 SL in Fibromyalgia
Regulatory Acceptance of Design of Registrational Clinical Studies; Dosing in First Safety and Efficacy Trial to Commence in the Third Quarter of 2013
NEW YORK, NY
March 11, 2013) – Tonix Pharmaceuticals Holding Corp. , a specialty pharmaceutical company developing novel treatments for challenging disorders of the central nervous system, including fibromyalgia (“FM”) and post-traumatic stress disorder (“PTSD”), announced that it recently held an End-of-Phase 2/Pre-Phase 3 meeting with the U.S. Food and Drug Administration (“FDA”) to discuss its proposed New Drug Application (“NDA”) plan for the Company’s novel sublingual tablet formulation of cyclobenzaprine for bedtime use, TNX-102 SL, for the management of FM. Official FDA meeting minutes indicate FDA acceptance of the clinical program and provide clear direction to achieve a successful NDA filing of TNX-102 SL in FM.
The registrational clinical trials will consist of two randomized, double-blind, placebo-controlled 12-week safety and efficacy studies in FM patients who will take either a TNX-102 SL (cyclobenzaprine HCl 2.8 mg) tablet or placebo at bedtime. The primary endpoint of both trials will be the change in pain from baseline to Week 12 as measured by the Numeric Rating Scale. The Company plans to conduct these trials in sequence, and expects to begin dosing in the first trial in the third quarter of 2013. This trial will enroll 100 to 200 FM patients, and top-line data are anticipated to become available in the second half of 2014.
Following the completion of the double-blind randomized portion of these studies, patients may be eligible to enroll in open-label extension studies of TNX-102 SL. The FDA agreed that the safety database needed to support a 505(b)(2) NDA submission for TNX-102 SL would contain a total exposure of at least 300 FM patients, with at least 100 patients receiving TNX-102 SL for six months and at least 50 patients for one year.
Seth Lederman, M.D., Chief Executive Officer of TONIX, said, “We view our meeting with the FDA as a major milestone for TONIX. We are pleased to have concurrence from the FDA on the design and selection of efficacy endpoints of our registrational clinical studies in FM in addition to receiving clear guidance on the remaining requirements for the TNX-102 SL NDA program. We are also pleased with the FDA’s requirements on chronic exposure, which are appropriately less than those typically needed for a new drug to be approved for a chronic use indication. We look forward to advancing TNX-102 SL towards a successful NDA filing.”
About Tonix Pharmaceuticals Holding Corp.
TONIX is developing innovative prescription medications for challenging disorders of the central nervous system. The Company targets conditions characterized by significant unmet medical need, inadequate existing treatment options, and high dissatisfaction among both patients and physicians. TONIX’s core technology improves the quality of sleep in patients with chronic pain syndromes, which is believed to translate into reductions in pain and other symptoms. An Investigational New Drug Application (“IND”) has been filed for the Company’s lead product candidate, TNX-102 SL, a novel under-the-tongue tablet formulation of cyclobenzaprine, the active ingredient in two FDA-approved muscle relaxants. TONIX expects to begin a registrational clinical study of TNX-102 SL in FM in the third quarter of 2013. TONIX expects to file an IND for TNX-102 SL in PTSD in the third quarter of 2013, and to begin a Phase 2 trial in this indication in the fourth quarter of 2013. To learn more, please visit www.tonixpharma.com.
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimated” and “intend,” among others. These forward-looking statements are based on TONIX’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, substantial competition; our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. TONIX does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K filed with the SEC on March 30, 2012 and future periodic reports filed with the Securities and Exchange Commission. All of the Company’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date hereof
Cyclobenzaprine, N,N-dimethyl-3-(dibenzo[a,d]cyclohepten-5-ylidene)propylamine, is synthesized by reacting 5H-dibenzo[a,d]cyclohepten-5-one with 3-dimethylaminopropylmagnesium chloride and subsequent dehydration of the resulting carbinol in acidic conditions into cyclobenzaprine. 
- H.La Roche, GB 858187 (1961).
- F.J. Villani, C.A. Ellis, C. Teihman, C. Biges, J. Med. Pharm. Chem., 5, 373 (1962).
- Winthrop, S. O.; Davis, M. A.; Myers, G. S.; Gavin, J. G.; Thomas, R.; Barber, R. (1962). “New Psychotropic Agents. Derivatives of Dibenzo[a,d]-1,4-cycloheptadiene”. The Journal of Organic Chemistry 27: 230. doi:10.1021/jo01048a057.
EU PIPELINE – Clinigen, Theravance sign Vibativ (telavancin) commercialization deal
Vibativ (telavancin)
12 MAR 2013
Clinigen Group and Theravance have signed an exclusive commercialization agreement for Vibativ (telavancin) in the EU and few other countries located in Europe.
The bactericidal, once-daily injectable lipoglycopeptide antibacterial agent is indicated for nosocomial pneumonia, including ventilator-associated pneumonia, believed to be caused by methicillin resistant Staphylococcus aureus when no other alternatives are suitable.
Clinigen chief executive officer Peter George said, “VIBATIV is a second product for Clinigen’s Specialty Pharmaceuticals (SP) portfolio, complementing the division’santi-viral product, Foscavir.”
Under the deal, Clinigen will make 5m upfront payment to Theravance that is even entitled to earn sales based royalties.
The agreement is signed for a minimum of 15 years, with an option to extend exercisable by Clinigen.
Theravance chief executive officer Rick Winningham said, “We look forward to working with Clinigen in making VIBATIV available to patients with nosocomial pneumonia in the EU.”
Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin.[1][2]
The FDA approved the drug in September 2009 for complicated skin and skin structure infections (cSSSI).[3]
On 19 November 2008, an FDA antiinfective drug advisory committee concluded that they would recommend telavancin be approved by the FDA.
The FDA approved the drug on 11 September 2009 for complicated skin and skin structure infections (cSSSI).[3]
Theravance has also submitted telavancin to the FDA in a second indication, nosocomial pneumonia, sometimes referred to as hospital-acquired pneumonia, or HAP. On 30 November 2012, an FDA advisory panel endorsed approval of a once-daily formulation of telavancin for nosocomial pneumonia when other alternatives are not suitable. However, telavancin did not win the advisory committee’s recommendation as first-line therapy for this indication. The committe indicated that the trial data did not prove “substantial evidence” of telavancin’s safety and efficacy in hospital-acquired pneumonia, including ventilator-associated pneumonia caused by Gram-positive organisms Staphylococcus aureus and Streptococcus pneumoniae.[5]
Like vancomycin, telavancin inhibits bacterial cell wall synthesis by binding to the D-Ala-D-Ala terminus of the peptidoglycan in the growing cell wall (see Pharmacology and chemistry of vancomycin). In addition, it disrupts bacterial membranes by depolarization.[2][6]
Telavancin has a higher rate of kidney failure than vancomycin in two clinical trials.[7] It showed teratogenic effects in animal studies.
- Astellas, Inc. VIBATIV prescribing information, 9/2009.
- Higgins, DL; Chang, R; Debabov, DV; Leung, J; Wu, T; Krause, KM; Sandvik, E; Hubbard, JM et al. (2005). “Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant Staphylococcus aureus”. Antimicrobial Agents and Chemotherapy 49 (3): 1127–1134. doi:10.1128/AAC.49.3.1127-1134.2005. PMC 549257.PMID 15728913.
- “Theravance and Astellas Announce FDA Approval of Vibativ (telavancin) for the Treatment of Complicated Skin and Skin Structure Infections” (Press release). Theravance, Inc. and Astellas Pharma US, Inc.. 2009-09-11. Retrieved 16 September 2009.
- “Drugs.com, FDA Accepts for Review Response to Approvable Letter for Telavancin”. Retrieved 2008-03-08.
- [1] FDA advisory group gives mixed review of Theravance pneumonia treatment . American City Business Journals/San Francisco/BiotechSF blog (11/30)
- H. Spreitzer (2 February 2009). “Neue Wirkstoffe – Telavancin” (in German). Österreichische Apothekerzeitung (3/2009).
- Saravolatz LD, Stein GE, Leonard B. Johnson LB. “Telavancin: a novel lipoglycopeptide”. Clinical Infectious Diseases 49 (12): 1908–1914. doi:10.1086/648438.
InnoPharma Inc. Announces Launch of Generic Cidofovir Injection in the United States
({[(S)-1-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
Cidofovir
Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus (CMV)retinitis[1] in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription.[2] It is an acyclic nucleoside phosphonate, and is therefore independent of phosphorylation by viral enzymes,[3] in contrast to, for instance, acyclovir.
Maintenance therapy with cidofovir involves an infusion only once every two weeks, making it a convenient treatment option. Because dosing is relatively infrequent, a permanent catheter is not necessary for infusions.
Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Holý, and developed by Gilead Sciences and is marketed with the brand name Vistide by Gilead in the USA, and by Pfizer elsewhere.
Synthesis
Brodfuehrer, P; Howell, Henry G.; Sapino, Chester; Vemishetti, Purushotham (1994). “A practical synthesis of (S)-HPMPC”.Tetrahedron Letters 35 (20): 3243. doi:10.1016/S0040-4039(00)76875-4.
March 8, 2013 — InnoPharma, Inc. today announced the launch of cidofovir injection (generic equivalent of Vistide(r)) in 5mL single-use vials. InnoPharma developed the generic formulation of cidofovir, which will be marketed in the United States by Mylan, Inc.
Cidofovir injection is indicated for the treatment of cytomegalovirus
(CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). For more information regarding this product, including its black box warning, please refer to the Mylan website at http://www.mylan.com.
About InnoPharma, Inc.
InnoPharma is a sterile product development company, focused on developing complex generic and innovative specialty pharmaceutical products in injectable and ophthalmic dosage forms. The Company has a broad portfolio of products under development, with formulations including solutions, suspension, lyophilized, emulsions, liposomes, micelles and lipid complexes. InnoPharma’s pipeline includes small molecules with solubility and stability challenges, as well as difficult to produce and characterize polypeptides and carbohydrates.
The Company has a comprehensive infrastructure for the development of its products in its state of the art R&D facilities in New Jersey, with the capability to handle potent and cytotoxic molecules. More information can be found at http://www.innopharmainc.com.
- Becker MN, Obraztsova M, Kern ER, et al. (2008). “Isolation and characterization of cidofovir resistant vaccinia viruses”.Virol. J. 5: 58. doi:10.1186/1743-422X-5-58. PMC 2397383.PMID 18479513.
- Cidofovir VIRUSES, HIV, PRIONS, AND RELATED TOPICS. Human Virology at Stanford University
- The mechanism of action of cidofovir and HSV helicase–primase complex inhibitors. Nature reviews
Phase 1- MERCK , Study of MK-8109 (Vintafolide) Given With Chemotherapy in Participants With Advanced Cancers
vintafolide
cas no 742092-03-1
http://www.ama-assn.org/resources/doc/usan/vintafolide.pdf
N-(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-γ-glutamyl-L-α- aspartyl-L-arginyl-L-α-aspartyl-L-α-aspartyl-L-cysteine disulfide with methyl (5S,7R,9S)- 5-ethyl-9-[(3aR,4R,5S,5aR,10bR,13aR)-3a-ethyl-4,5-dihydroxy-8-methoxy-6-methyl-5- ({2-[(2-sulfanylethoxy)carbonyl]hydrazinyl}carbonyl)-3a,4,5,5a,6,11,12,13a-octahydro- 1H-indolizino[8,1-cd]carbazol-9-yl]-5-hydroxy-1,4,5,6,7,8,9,10-octahydro-2H-3,7- methanoazacycloundecino[5,4-b]indol-9-carboxylate
Vincaleukoblastin-23-oic acid, O4-deacetyl-, 2-[(2-mercaptoethoxy)carbonyl]hydrazide, disulfide with N-[4-[[(2-amino-3,4-dihydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-γ- glutamyl-L-α-aspartyl-L-arginyl-L-α-aspartyl-L-α-aspartyl-L-cysteine
Vintafolide is a water-soluble, folate-receptor-targeted conjugate of folate and the vinca alkaloid desacetylvinblastine monohydrazide (DAVLBH) with potential antineoplastic activity. The folate moiety of folate-vinca alkaloid conjugate EC145 binds to folic acid receptors on the tumor cell surface and the agent is internalized via folate receptor-mediated endocytosis, delivering the tubulin-binding DAVLBH moiety directly into the tumor cell; DAVLBH binding to tubulin results in the disruption of microtubule assembly-disassembly dynamics, cell cycle arrest, and tumor cell apoptosis. Folic acid receptors are frequently upregulated on the surfaces of many tumor cell types. DAVLBH is a derivative of the natural product vinblastine.
http://clinicaltrials.gov/show/NCT01688791
ClinicalTrials.gov Identifier:
Vintafolide is a derivative of the anti-mitotic chemotherapy drug vinblastine.[1] chemically linked to folic acid. The vintafolide molecule was designed to specifically target the toxic vinblastine group to cancer cellsthat overexpress the folic acid receptor.[2] Vintafolide is being studied for treatment of late-stage ovarian cancer and mid-stage non-small cell lung cancer.
Merck & Co. acquired the development and marketing rights to this experimental cancer drug from Endocyte in April 2012. Endocyte had planned to file for marketing approval for vintafolide in the third quarter of 2012. The drug received an orphan drug status in Europe in March 2012.[3] Endocyte remains responsible for the development and commercialization of etarfolatide, a non-invasive companion diagnostic imaging agent used to identify folate receptor positive tumor cells that may be susceptible to vintafolide.[4]
- Statement on a nonproprietary name adopted by the USAN Council, United States Adopted Names (USAN) Council, 6 April 2012
- Dosio F, Milla P, Cattel L. EC-145, a folate-targeted Vinca alkaloid conjugate for the potential treatment of folate receptor-expressing cancers. Curr Opin Investig Drugs. 2010 Dec;11(12):1424-33. Review. PubMed PMID: 21154124.
- Endocyte soars on cancer drug deal with Merck, Reuters, US Edition, Mon Apr 16, 2012.
- Merck, Endocyte in Development Deal Wed, Drug Discovery and Development. 04/25/2012
Chemical structure of EC-145
(source: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2011, 336(2):336–343)
Phase 2 ORM-12741, Orion’s Experimental Alzheimer’s Drug Shows Promise, Study Finds
 ORM-12741 in WO 2003082866 |
The purpose of this study is to determine whether ORM-12741 is safe and effective in the treatment of Alzheimer’s disease.,
March 11, 2013
A small Finnish study is raising hopes for a new drug designed to help stave off memory loss among patients struggling with moderate Alzheimer’s disease.
Still in the preliminary stages of investigation, the drug — called ORM-12741 — showed promise during a three-month trial involving 100 such patients, half of whom were given the medication on top of their current drug treatment.
By the end of the study, memory scores plummeted by 33 percent among the 50 patients who were given a dummy pill (placebo) rather than the new drug, while patients who took the new drug showed a 4 percent improvement on the tests.
“The bottom line is that this was the first study investigating [effectiveness] of a drug with a novel mechanism of action in patients with Alzheimer’s disease,” said study lead author Dr. Juha Rouru, who heads the central nervous system therapy area at Orion Pharma in Turku, Finland.
“The results were clearly positive,” he said, adding they were seen particularly on important episodic memory, which involves remembering events and personal experiences. Orion, the maker of ORM-12741, funded the research.
Rouru and his colleagues are scheduled to present their work in San Diego at a meeting of the American Academy of Neurology, which starts Saturday.
By 2050, as the elderly population increases, an estimated 13.8 million Americans will have Alzheimer’s, a progressive brain disease that robs people of their memory and the ability to perform even simple everyday tasks. There is no cure for the disease, and drugs aimed at controlling the debilitating symptoms are only moderately effective, Rouru said.
With that in mind, the team set out to assess the potential of ORM-12741, the first drug to target a specific receptor in the brain, called alpha-2C. This receptor is thought to play a role in the brain’s “fight or flight” response to stress, and the authors noted that the new drug’s impact on alpha-2C had shown promise in prior animal studies.
All the patients in the study were already taking a cholinesterase drug. Some were also using memantine, another type of Alzheimer’s medication.
Fifty patients were then given a placebo on top of their current regimen, while 50 were given either a low-dose (30 to 60 milligrams) twice daily supply of ORM-12741 or a high-dose (100 to 200 milligrams) version.
Computerized memory tests highlighted an apparent memory benefit (without prompting severe side effects) among the ORM-12741 patients, and Rouru suggested that the new drug should be seen as just one more potentially effective tool in an ongoing battle to reign in “a devastating disease.”
“I am afraid that wonder drugs hardly exist,” he noted. “In the present study, our drug was used on top of existing Alzheimer’s medications. In that setting it showed clear effect, which suggests that it is giving additional clinically significant benefit for patients that are already using Alzheimer’s medications.”
Catherine Roe, an assistant professor of neurology at Washington University School of Medicine in St. Louis, described Rouru’s research as “impressive.”
“This is really a new approach, in terms of the biology that they’re targeting,” she noted. “And they showed significant results after only three months of treatment, which is exciting particularly because this drug combination was tested on people who had moderate Alzheimer’s disease.”
Many experts have thought moderate Alzheimer’s disease would be untreatable, she said. “By the time it’s that advanced, the nerves have already died and it would be too late to do anything about memory by this stage,” she explained.
Still, much more testing will need to be done, Roe cautioned. “And these results will have to be replicated with other groups of people,” she said. “But if they can do that, this would be awesome.”
The data and conclusions of research presented at medical meetings are typically considered preliminary until published in a peer-reviewed journal.
More information
For more on Alzheimer’s disease, visit the U.S. National Institutes of Health.
Sunovion Announces FDA Acceptance for Review of New Drug Application Resubmission for Stedesa (eslicarbazepine acetate)
eslicarbazepine
(S)-10-Acetoxy- 10,11-dihydro- 5H-dibenz[b,f]azepine- 5-carboxamide
Sunovion Announces FDA Acceptance for Review of New Drug Application Resubmission for Stedesa (eslicarbazepine acetate) as a Once-Daily Adjunctive Therapy for Partial-onset Seizures in Adults with Epilepsy
MARLBOROUGH, Feb 27, 2013
Sunovion Pharmaceuticals Inc. (Sunovion) today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the Company’s New Drug Application (NDA) resubmission for Stedesa® (eslicarbazepine acetate) for use as a once-daily adjunctive therapy in the treatment of partial-onset seizures in patients 18 years and older with epilepsy. Stedesa is the proposed trade name for eslicarbazepine acetate.
“We are pleased to achieve this regulatory milestone for Stedesa, which, if approved, may offer adult patients living with epilepsy an effective, once-daily, adjunctive treatment option for managing partial-onset seizures,” said Fred Grossman, D.O., FAPA, Senior Vice President, Clinical Development and Medical Affairs at Sunovion. “Adequate seizure control of this most common form of epilepsy remains an unmet medical need for a significant number of patients and Sunovion is committed to providing a treatment option to help address this need.”
The NDA for Stedesa is supported by data from three Phase III randomized, double-blind, placebo-controlled 12-week maintenance trials of similar study design, which included more than 1,300 patients with partial-onset seizures in 35 countries, including the United States. Treatment with Stedesa demonstrated statistically significant reductions in standardized seizure frequency when used as adjunctive therapy. The most commonly reported adverse events in the clinical trials were dizziness, somnolence, headache, nausea, diplopia, vomiting, fatigue, ataxia, vision blurred, and vertigo.
The original NDA was submitted to the FDA in March 2009. This resubmission was prepared by Sunovion following receipt of the FDA’s April 2010 Complete Response Letter and subsequent correspondence requesting additional information. Eslicarbazepine acetate is currently marketed in Europe by BIAL-Portela & Cª, S.A and by BIAL´s licensee, Eisai Europe Limited, a UK subsidiary of Eisai Co., Ltd. under the trade name Zebinix®. Zebinix® was approved by the European Commission on April 21, 2009 as adjunctive therapy in adult patients with partial-onset seizures with or without secondary generalization.
Sunovion and BIAL are also conducting clinical trials to evaluate eslicarbazepine acetate as monotherapy in the treatment of partial-onset seizures in adult patients with epilepsy.
Epilepsy is one of the most common neurological disorders and, according to the Centers for Disease Control and Prevention, affects nearly 2.2 million people in the United States.1 It is characterized by abnormal firing of impulses from nerve cells in the brain.2 In partial-onset seizures, these bursts of electrical activity are initially focused in specific areas of the brain, but may become more widespread, with symptoms varying according to the affected areas.3,4
Stedesa (eslicarbazepine acetate) is an investigational voltage-gated sodium and T-type calcium channel blocker that has been evaluated in three Phase III clinical trials involving more than 1,300 patients with partial-onset epilepsy worldwide. BIAL-Portela & Cª, S.A., a privately held Portuguese research based pharmaceutical company, was responsible for the initial research and development of eslicarbazepine acetate. In late 2007, Sunovion Pharmaceuticals Inc., formerly known as Sepracor Inc., acquired the rights to further develop and commercialize eslicarbazepine acetate in the U.S. and Canadian markets from BIAL.
Sunovion is a leading pharmaceutical company dedicated to discovering, developing and commercializing therapeutic products that advance the science of medicine in the Psychiatry & Neurology and Respiratory disease areas and improve the lives of patients and their families. Sunovion’s drug development program, together with its corporate development and licensing efforts, has yielded a portfolio of pharmaceutical products including LATUDA® (lurasidone HCl) tablets, LUNESTA® (eszopiclone) tablets, XOPENEX® (levalbuterol HCI) inhalation solution, XOPENEX HFA® (levalbuterol tartrate) inhalation aerosol, BROVANA® (arformoterol tartrate) inhalation solution, OMNARIS® (ciclesonide) nasal spray, ZETONNA® (ciclesonide) nasal aerosol and ALVESCO® (ciclesonide) inhalation aerosol.
Sunovion, an indirect, wholly-owned subsidiary of Dainippon Sumitomo Pharma Co., Ltd., is headquartered in Marlborough, Mass. More information about Sunovion Pharmaceuticals Inc. is available at www.sunovion.com.
DSP is a multi-billion dollar, top-ten listed pharmaceutical company in Japan with a diverse portfolio of pharmaceutical, animal health and food and specialty products. DSP aims to produce innovative pharmaceutical products in the Psychiatry & Neurology field, which has been designated as one of the two key therapeutic areas. DSP is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, DSP has more than 7,000 employees worldwide. Additional information about DSP is available through its corporate website at www.ds-pharma.com.
STEDESA is a registered trademark of Bial – Portela & Cª, S.A., used under license.
Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. © 2013 Sunovion Pharmaceuticals Inc.
For a copy of this release, visit Sunovion’s web site at www.sunovion.com
Eslicarbazepine acetate (BIA 2-093) is an antiepileptic drug. It is a prodrug which is activated to eslicarbazepine (S-licarbazepine), an active metabolite of oxcarbazepine.[1]
It is being developed by Bial[2] and will be marketed as Zebinix or Exalief by Eisai Co. in Europe and as Stedesa by Sepracor[3] in America.
The European Medicines Agency (EMA) has recommended granting marketing authorization in 2009 for adjunctive therapy for partial-onset seizures, with or without secondary generalisation, in adults with epilepsy.[1] The U.S. Food and Drug Administration (FDA) announced on 2 June 2009 that the drug has been accepted for filing.[3]
Eslicarbazepine acetate is a prodrug for S(+)-licarbazepine, the major active metabolite of oxcarbazepine.[4] Its mechanism of action is therefore identical to that of oxcarbazepine. [5] There may, however, be pharmacokinetic differences. Eslicarbazepine acetate may not produce as high peak levels of (S)-(+)-licarbazepine immediately after dosing as does oxcarbazepine which could theoretically improve tolerability.
Like oxcarbazepine, eslicarbazepine may be used to treat bipolar disorder and trigeminal neuralgia.
Patents
The first European patent to protect this drug is EP 0751129. The priority of this European patent is the Portuguese patent application PT 101732.
References
- Dulsat, C., Mealy, N., Castaner, R., Bolos, J. (2009). “Eslicarbazepine acetate”. Drugs of the Future 34 (3): 189. doi:10.1358/dof.2009.034.03.1352675.
- Community register of medicinal products for human use: Exalief
- Medical News Today: Sepracor’s STEDESA (Eslicarbazepine Acetate) New Drug Application Formally Accepted For Review By The FDA
- Rogawski, MA (Jun 2006). “Diverse Mechanisms of Antiepileptic Drugs in the Development Pipeline”. Epilepsy Res 69 (3): 273–294. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526. PMID 16621450.
- Rogawski MA, Löscher W (July 2004). “The neurobiology of antiepileptic drugs”. Nature Reviews Neuroscience 5 (7): 553–64. doi:10.1038/nrn1430. PMID 15208697.
Health Canada approval-aHUS Canada applauds approval of Soliris® (eculizumab) first treatment for fatal, ultra-rare disease affecting children and adults
CAS number 219685-50-4
Soliris is a formulation of eculizumab which is a recombinant humanized monoclonal IgG2/4;κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa.
TORONTO, March 7, 2013
Atypical Hemolytic Uremic Syndrome (aHUS) Canada is thrilled by Health Canada’s recent approval of Soliris® (eculizumab) for the treatment of patients with atypical Hemolytic Uremic Syndrome (aHUS), 1 a very rare, chronic and life-threatening genetic condition affecting fewer than 60 patients in Canada.
aHUS leaves a part of the immune system (known as the complement system) uncontrolled and always active. As a result, the immune system attacks the body’s unhealthy and healthy cells which can cause blood vessel damage, abnormal blood clotting 2,3 and progressive damage to the body’s major organs, leading to heart attack, stroke, kidney failure and death.4
The management of aHUS has relied on plasma infusion and plasma exchange therapies with variable results.5 These lifelong therapies are costly, painful and time-consuming, and have not been studied or approved for the treatment of aHUS.6 If kidney failure has already occurred as a result of aHUS, dialysis is required, though it is not a curative treatment.7 Within a year of diagnosis, over half of patients will need dialysis, will have irreversible kidney damage, or will not survive.6 The majority of patients progress to end-stage kidney failure within three years of diagnosis.8,9
With the approval of Soliris, aHUS patients and their families finally have a reason for hope.
Sonia DeBortoli knows all too well the destructive force of the disease. Sonia’s 11-year-old son Joshua was diagnosed with aHUS in March 2012 and experienced kidney failure, internal bleeding and a blood clot in his groin as a result. He endured several painful hours of daily dialysis and plasma therapy, and was on prednisone and oxygen. Then, a chance to join a clinical trial for Soliris restored Joshua’s health so that he no longer needed the other therapies.
“Our whole world changed when Joshua was given Soliris – we now believe he has a long and healthy future. He is back at school, taking karate lessons and playing soccer,” Sonia says. “We got our little boy back, he got his life back, and we want the same for anyone who has to deal with this rare and devastating disease.”
A groundbreaking treatment advance for aHUS patients
Soliris (eculizumab) is the first and only pharmaceutical treatment for aHUS, and is being hailed by experts worldwide as a critical breakthrough in treating the disease. It has been shown to significantly improve patients’ health and quality of life.10 In clinical trials, Soliris has been proven effective in preventing blood vessel damage and abnormal blood clotting,11,12 leading to remission and significant improvement in kidney function.5,4 Soliris has also allowed patients to discontinue dialysis and plasma exchange therapies.10
Soliris is also indicated, and proven safe and effective, for the treatment of another rare and life-threatening disorder called paroxysmal nocturnal hemoglobinuria (PNH).13 Canadians living with PNH already have access to Soliris through private health insurance and provincial drug plans.
Immediate and sustained access to treatment urgently needed
Now that this new treatment option has been approved for the small number of Canadians living with the devastating symptoms of aHUS, Soliris must be made immediately accessible to all aHUS patients whose lives depend on this treatment.
“We are so hopeful that the Common Drug Review will recognize the urgent need for access to Soliris, and that provincial governments will act swiftly to provide reimbursement to patients who are in urgent need of this life-saving treatment,” says Tracy MacIntyre, a founder of aHUS Canada whose daughter is living with aHUS. “Immediate access to the drug would have a profoundly positive impact on the few Canadians living with aHUS, while any delay in funding treatment could lead to devastating consequences.”
About aHUS Canada
aHUS Canada was formed in November 2012 to support Canadian patients and families living with aHUS. In addition to establishing a Canadian aHUS community, the group is committed to building public awareness and understanding of aHUS and advocating for the best possible care and treatment for patients. For more information, please visit http://www.ahuscanada.org.
Eculizumab (INN and USAN; trade name Soliris®) is a humanized monoclonal antibody that is a first-in-class terminal complement inhibitor and the first therapy approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a rare, progressive, and sometimes life-threatening disease characterized by excessive destruction of red blood cells (hemolysis).[1] It costs £400,000 ($US 600,000) per year per patient.[1]
Eculizumab also is the first agent approved for the treatment of atypical hemolytic uremic syndrome (aHUS), an ultra-rare genetic disease that causes abnormal blood clots to form in small blood vessels throughout the body, leading to kidney failure, damage to other vital organs and premature death.[2][3]
In clinical trials in patients with PNH, eculizumab was associated with reductions in chronic hemolysis, thromboembolic events, and transfusion requirements, as well as improvements in PNH symptoms, quality of life, and survival.[1][4][5][6] Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),[7] the formation of blood clots in small blood vessels throughout the body,[1][3][4] including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.[7]
Eculizumab was discovered and developed by Alexion Pharmaceuticals and is manufactured by Alexion. It was approved by the United States Food and Drug Administration (FDA) on March 16, 2007 for the treatment of PNH, and on September 23, 2011 for the treatment of aHUS. It was approved by the European Medicines Agency for the treatment of PNH on June 20, 2007, and on November 24, 2011 for the treatment of aHUS. Eculizumab is currently being investigated as a potential treatment for other severe, ultra-rare disorders
- Hillmen, Young, Schubert, P, N, J, et al (2006). “The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria”. N Engl J Med 355 (12): 1233–1243. doi:10.1056/NEJMMoa061648. PMID 16990386.
- Noris, Caprioli, Bresin, M, J, E, et al. (2010). “Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype”. Clin J Am Soc Nephrol 5: 1844–1859.
- Caprioli, Noris, Brioschi, J, M, S, et al (2006). “Genetics of HUS: the impact of MPC, CFH, and IF mutations on clinical presentation, response to treatment, and outcome”. Blood 108: 1267–1279.
- Hillman, Hall, Marsh, P, C, JC, et al (2004). “Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria”. N Eng J Med 350: 552–559.
- Ray, Burrows, Ginsberg, Burrows, JG, RF, JS, EA (2000). “Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: review and recommendations for management of the pregnant and nonpregnant patient”. Haemostasis 30: 103–107.
- Kelly, Hill, Arnold, RJ, A, LM, et al (2011). “Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival”. Blood 117: 6786–6792.
- .Soliris® (eculizumab) prescribing information (2011). Cheshire, CT: Alexion Pharmaceuticals. http://www.soliris.net/sites/default/files/assets/soliris)pi.pdf.
Phase 2, Sarepta Therapeutics, Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy
Eteplirsen, also called AVI-4658, is an experimental drug, currently in clinical trials. It is designed for treatment of some mutations which cause Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease. Eteplirsen is a product of Sarepta Therapeutics Inc.
s excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin;[1] giving eteplirsen to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional (though internally-truncated) dystrophin.[2] Eteplirsen is given by intravenous infusion for systemic treatment of DMD.
Clinical studies
Several clinical trials have been conducted to test eteplirsen, one in the UK involving local injection to the foot,[3][4] one in the UK involving systemic injection at low doses[5][6] and one in the USA at higher systemic doses[7] that progressed to a rollover extension study.[8]
References
- “Exon Skipping Quantification by qRT-PCR in Duchenne Muscular Dystrophy Patients Treated with the Antisense Oligomer Eteplirsen”. Hum Gene Ther Methods.. 17 Oct 2012.
- “Morpholinos and Their Peptide Conjugates: Therapeutic Promise and Challenge for Duchenne Muscular Dystrophy.”. Biochim Biophys Acta. 1798 (12): 2296–303.. 17 Feb 2010.
- Gary Roper/Manager Clinical Research Governance Organisation, Imperial College London. “Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- Lancet Neurol. 8 (10): 918–28. 25 Aug 2009.
- Professor Francesco Muntoni, University College of London Institute of Child Health. “Dose-Ranging Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy (DMD) Patients”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- “Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study.”. Lancet. 378 (9791): 595–605. 23 Jul 2011.
- Sarepta Therapeutics. “Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- Sarepta Therapeutics. “Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
Phase 2 Drug: Ustekinumab A monoclonal antibody against the p40 subunit of IL-12/23 Other Name: Stelara
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | IL-12 and IL-23
|
Ustekinumab, CAS number 815610-63-0, is also known by it’s brand name Stelara, which is marketed by Janssen Biotech, Inc. Developed as a treatment for adults with moderate to severe plaque psoriasis
Rockefeller University, MAR 2013
http://clinicaltrials.gov/ct2/show/NCT01806662
Atopic dermatitis (AD) is a chronic disease associated with intense itching, which affects most aspects of everyday life in the majority of patients. Acute inflammation and extensor/facial involvement is common in infants, whereas chronic inflammation increases in prevalence with age, as do localization to flexures. AD has a complex background characterized by immune activation, increased epidermal thickness in chronic diseased skin, and defective barrier function. In normal, healthy skin, the outer layer of the epidermis, the stratum corneum is made up flattened dead cells called corneocytes held together by a mixture of lipids and proteins. The stratum corneum and, in particular, the lipid layer are vital in providing a natural barrier function that locks water inside the skin and keeps allergens and irritants out. In people with AD, the barrier function is defective, which leads to dry skin. As the skin dries out, it cracks allowing allergens and irritants to penetrate.
Mild AD can be controlled with emollients and topical medications. However, moderate to severe AD is extremely difficult to control and requires systemic treatment that is often unsatisfactory due to impracticality and lack of effectiveness. Only three therapeutic options exist for moderate to severe AD, including: 1) oral steroids 2) cyclosporine A (CsA), that is not widely used in the US as it is not FDA approved for AD and 3) ultraviolet phototherapy. Oral steroids and CsA treatments have major side effects and UV radiation therapy is highly inconvenient for patients. Several biologic medications, such as TNF-alpha inhibitors, are effective, convenient, and relatively safe therapies for psoriasis, but have thus far not shown efficacy in AD. Ustekinumab is a unique biologic medication that may specifically target AD.
The investigators study will determine whether there is a reversal of the skin thickness and the immune pathways involved in the disease during treatment with Ustekinimab and what specific immune cells are involved. The investigators are also interested to understand how the clinical reversal of the disease will correlate with tissue reversal of the disease.
Detailed Description:
In psoriasis, epidermal hyperplasia is driven by underlying immune activation, whether as a direct response to IL-20 family cytokines that induces hyperplasia and inhibits keratinocyte terminal differentiation or as an indirect response to immune-mediated injury to keratinocytes. The epidermal reaction in psoriasis is largely restored to normal with selective immune suppression. Hence, one might hypothesize that similar epidermal responses should occur in the presence of “generalized” cellular immune activation, in diseases with similar inflammatory infiltrate and epidermal hyperplasia, such as AD. In fact, psoriasis and AD share features of dense T-cells and dentritic cell infiltrates, as well as over-expression of IL-22 in skin lesions. These diseases also share similar epidermal hyperplasia in their chronic phases.
Work from the investigators group showed that IL-22 is a key cytokine in the pathogenesis of both AD and psoriasis. The investigators have demonstrated that in psoriasis, ustekinumab suppresses the production of IL-12, IL-23, and IL-22. Additionally, by RT-PCR the investigators demonstrated that the mRNA expression of p40 cytokine and the IL23R is up-regulated in AD as compared to both normal skin and psoriasis. The investigators therefore hypothesize that ustekinumab will suppress IL-22 and possibly also p40 production in AD lesions and reverse both the epidermal growth/differentiation defects and the underlying immune activation, and hence will suppress disease activity. Interestingly, p40 was also found to be significantly up-regulated in non-lesional AD skin as compared with normal skin.
Although AD is thought to be predominately a disease of Th2-type cells, in the chronic stage, there is large Th1 component. To date, the precise mechanism by which sequential activation of Th2 and Th1 cells in AD is achieved remains unknown. IL-12 induces the differentiation and maturation of human Th cells into Th1-type cells. Recent circumstantial evidence suggests that in AD patients IL-12 may facilitate a change from the Th2-type to a Th1 cytokine profile. IL-12 was recently shown to be highly elevated in pediatric AD and its levels were strongly associated with disease severity.
Expression of IL-12 p40 mRNA is significantly enhanced in lesional skin from AD, suggesting that the enhanced local production of IL-12 in dendritic cells and macrophages may be responsible for the increased production of IFN-γ in chronic lesions potentially suggesting that IL-12 may have a pivotal role in promoting inflammation in atopic dermatitis. Topical steroids which constitute a mainstay of therapy in AD are known to strongly down-regulate IL-12 expression, possibly also indicating that targeted anti IL-12 therapy might important role in treating AD.
Recently, the Th1/Th2 paradigm in autoimmunity and allergy has been revisited to include a role for a new population of IL-17-producing Th cells known as Th17. Th17 cells are characterized by the production of inflammatory cytokines such as IL-17A, IL-17F, IL-22, and IL-26. One of the key factors involved in naive Th-cell commitment to a Th17 phenotype is IL-23.
Patients with acute AD were found to have increased Th17 T-cells in peripheral blood by flow cytometry and intracellular cytokine staining 26 as well as by immunohistochemistry (IHC) in lesions. Since IL-23 is the major inducer of Th17 T-cells, as well as “T22” T-cells, neutralization of IL-23 could potentially result in both decreased Th17 signal in acute AD as well as decreased “T22/IL22″ signal. Therefore the investigators postulate that ustekinumab in AD will act both inhibiting the IL-12-dependent Th1 shift in chronic AD stage as well as the pathogenic IL-22/”T22” axis in this disease.
Ustekinumab [1] (INN, experimental name CNTO 1275, proprietary commercial name Stelara,[2] Centocor) is a human monoclonal antibody. It is directed against interleukin 12 and interleukin 23, naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.[3]
In two Phase III trials for moderate to severe psoriasis, the longest >76 weeks, ustekinumab was safe and effective.[4][5]
A third Phase III trial, ACCEPT, compared the efficacy and safety of ustekinumab with etanercept in the treatment of moderate to severe plaque psoriasis.[6] This trial found a significantly higher clinical response with ustekinumab over the 12-week study period compared to high-dose etanercept.[6] It also demonstrated the clinical benefit of ustekinumab among patients who failed to respond to etanercept.[6]
Ustekinumab is approved in Canada, Europe and the United States to treat moderate to severe plaque psoriasis.[7]
As of November 2009, the drug is being investigated for the treatment of psoriatic arthritis.[8][9] It has also been tested in Phase II studies for multiple sclerosis[10] and sarcoidosis, the latter versus golimumab (Simponi).[11]
- Cingoz, Oya (2009). “Ustekinumab”. MAbs 1 (3): 216–221. doi:10.4161/mabs.1.3.8593. PMC 2726595. PMID 20069753.
- ^ European Medicines Agency, 20 November 2008, http://www.emea.europa.eu/pdfs/human/opinion/Stelara_58227008en.pdf
- ^ Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U (May 2007). “Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275”. Cell. Immunol. 247 (1): 1–11. doi:10.1016/j.cellimm.2007.06.006. PMID 17761156.
- ^ Leonardi CL, Kimball AB, Papp KA, et al. (May 2008). “Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1)”. Lancet 371 (9625): 1665–74. doi:10.1016/S0140-6736(08)60725-4. PMID 18486739.
- ^ Papp KA, Langley RG, Lebwohl M, et al. (May 2008). “Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)”. Lancet 371 (9625): 1675–84. doi:10.1016/S0140-6736(08)60726-6. PMID 18486740.
- ^ a b c Griffiths C, Strober B, van de Kerkhof P et al. (2010). “Comparison of Ustekinumab and Etanercept for Moderate-to-Severe Psoriasis”. N Engl J Med 362 (2): 118–28. doi:10.1056/NEJMoa0810652. PMID 20071701.
- ^ Medarex to Receive Milestone Payment for Approval of STELARA(TM) (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis
- ^ ClinicalTrials.gov NCT00267956 A Study of the Safety and Efficacy of CNTO 1275 in Patients With Active Psoriatic Arthritis
- ^ ClinicalTrials.gov NCT01009086 A Study of the Safety and Efficacy of Ustekinumab in Patients With Psoriatic Arthritis
- ^ ClinicalTrials.gov NCT00207727 A Safety and Efficacy Study of CNTO1275 in Patients With Multiple Sclerosis
- ^ ClinicalTrials.gov NCT00955279 A Study to Evaluate the Safety and Effectiveness of Ustekinumab or Golimumab Administered Subcutaneously (SC) in Patients With Sarcoidosis
- ^ http://www.empr.com/stelara-approved-for-moderate-to-severe-psoriasis/article/149760/
- ^ a b Centocor 12/19/08 Press Release, http://www.centocor.com/centocor/i/press_releases/FDA_ISSUES_COMPLETE_RESPONSE_LETTER_TO_CENTOCOR_FOR_USTEKINUMAB_BIOLOGIC_LICENSE_APPLICATION_
- ^ Johnson LL. “Study: Drug for serious psoriasis tops competition” The Associated Press. 18 Sept 2008.[dead link]
- ^ Wild, David (November 2011), “Novel IL-12/23 Antagonist Shows Potential in Severe Crohn’s”, Gastroenterology & Endoscopy News 62 (11), retrieved 2011-12-04
- ^ a b c Weber J, Keam SJ (2009). “Ustekinumab”. BioDrugs 23 (1): 53–61. doi:10.2165/00063030-200923010-00006. PMID 19344192.
- ^ Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH (September 2008). “Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study”. Lancet Neurol 7 (9): 796–804. doi:10.1016/S1474-4422(08)70173-X. PMID 18703004.
- ^ “Important Safety Information”. STELARA® (ustekinumab). Janssen Biotech.
External links
- Centocor Ortho Biotech official site
- CNTO 1275 research studies registered with U.S. National Institutes of Health:
- ClinicalTrials.gov NCT00207727 Phase II Study on Multiple Sclerosis
- ClinicalTrials.gov NCT00320216 Phase II Study on Psoriasis
- ClinicalTrials.gov NCT00267969 Phase III Study on Psoriasis
- ClinicalTrials.gov NCT00307437 Phase III Study on Psoriasis
- ClinicalTrials.gov NCT00267956 Phase II Study on Psoriatic Arthritis
- Sylvester, Bruce (2006-03-06). “CNTO 1275 Shows Efficacy for Psoriasis: Presented at AAD”. Doctor’s Guide Publishing. Retrieved 2007-01-25.
10 MAR 2013, MAA EU SUBMITTED, APPROVED US, CANADA, LURASIDONE, LATUDA, SCHIZOPRENIA, DAINIPPON SUMITOMO
LURASIDONE
(3aR,4S,7R,7aS)-2-[((1R,2R)-2-{[4-(1,2-benzisothiazol-3-yl)-piperazin-1-yl]methyl}cyclohexyl)methyl]hexahydro-1H-4,7-methanisoindol-1,3-dione
STATUS AS ON 10 MARCH 2012
Lurasidone (trade name Latuda) is an atypical antipsychotic developed by Dainippon Sumitomo Pharma.[1] It was approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia on October 28, 2010[2] after a review that found that two of the four Phase III clinical trials supported efficacy, while one showed only marginal efficacy and one was not interpretable because of high drop-out rates.[3] It is currently pending approval for the treatment of bipolar disorder in the United States.
Clinical effects
In clinical studies, lurasidone alleviates positive symptoms (e.g., hallucinations, delusions) without inducing extrapyramidal side effects except for akathisia,[4] despite its potent D2 antagonistic actions. Effectiveness against negative symptoms of schizophrenia has yet to be established.
Lurasidone may be useful for treating the cognitive and memory deficits seen in schizophrenia. In animal studies, it reversed dizocilpine-induced learning and memory impairment and was found to be superior in doing this to all of the other antipsychotics examined, including risperidone, olanzapine, quetiapine, clozapine, aripiprazole, and haloperidol.[5][6] Lurasidone has activity at several serotonin receptors that are involved in learning and memory, and unlike most other antipsychotics, lacks any anticholinergic effects (which are known to impair cognitive processes and memory).[5] These properties may underlie its improved effectiveness in treating these symptoms relative to older agents.[5]
References
- Meyer JM, Loebel AD, Schweizer E (September 2009). “Lurasidone: a new drug in development for schizophrenia”. Expert Opinion on Investigational Drugs 18 (11): 1715–26. doi:10.1517/13543780903286388. PMID 19780705.
- “FDA approves Latuda to treat schizophrenia in adults” (Press release). USFDA. 2010-10-28. Retrieved October 29, 2010.
- FDA Clinical Review of lurasidone for the treatment of schizophrenia Nakamura M, Ogasa M, Guarino J, et al. (June 2009).
- “Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial”. The Journal of Clinical Psychiatry 70 (6): 829–36. doi:10.4088/JCP.08m04905. PMID 19497249.
- Ishiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y (October 2007). “Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test”. European Journal of Pharmacology 572 (2-3): 160–70. doi:10.1016/j.ejphar.2007.06.058. PMID 17662268.
- Enomoto T, Ishibashi T, Tokuda K, Ishiyama T, Toma S, Ito A (January 2008). “Lurasidone reverses MK-801-induced impairment of learning and memory in the Morris water maze and radial-arm maze tests in rats”. Behavioural Brain Research 186 (2): 197–207. doi:10.1016/j.bbr.2007.08.012. PMID 17881065.
- Dainippon Sumitomo Pharma (August 26, 2009). “Lurasidone Demonstrated Efficacy in Treating Patients with Schizophrenia in Pivotal Phase III Study”.
- “Latuda: Prescribing Information”. Psychotherapeutic Drugs. Retrieved 2010-12-17.
- “Latuda”. Drugs.com. Retrieved 2010-12-17.
- “Atypical antipsychotics and risk of cerebrovascular accidents”. Retrieved 28 July 2012.
LATUDA® (lurasidone hydrochloride) Schizophrenia，Bipolar disorder
- Developed in-house
- LATUDA® (lurasidone hydrochloride) is an atypical antipsychotic agent which is believed to have an affinity for dopamine D2, serotonin 5-HT2A and serotonin 5-HT7 receptors where it has antagonist effects. In addition, LATUDA is a partial agonist at the serotonin 5-HT1A receptor and has no appreciable affinity for histamine or muscarinic receptors. In the clinical trials supporting the U.S. FDA approval, the efficacy of LATUDA for the treatment of schizophrenia was established in four, short-term (6-week), placebo-controlled clinical studies in adult patients who met DSM-IV criteria for schizophrenia. In these studies, LATUDA demonstrated significantly greater improvement versus placebo on the primary efficacy measures [the Positive and Negative Syndrome Scale (PANSS) total score and the Brief Psychiatric Rating Scale-derived from PANSS (BPRSd)] at study endpoint. A total of five short-term placebo controlled clinical trials contributed to the understanding of the tolerability and safety profile of LATUDA. LATUDA was approved for the treatment of schizophrenia by the U.S. Food and Drug Administration (FDA) in October 2010, and launched by Sunovion in February 2011 in the U.S. Launched in Canada for the treatment of schizophrenia in September 2012.
- Development stage:
Schizophrenia: Submitted MAA (Europe: Co-development with Takeda Pharmaceutical)
Phase III in Japan
In addition, Phase III study is ongoing in the U.S., Europe, etc. to test the hypothesis that LATUDA is effective in the long term maintenance treatment of schizophrenia.Bipolar I Depression: Submitted in the U.S. and Canada.
In addition, plans to submit an MAA in Europe through Co-development with Takeda Pharmaceutical. (Phase III in Europe).Bipolar Maintenance: Phase III in the U.S. and Europe, etc. MDD with mixed features: Phase III in the U.S
New Drug Approvals 
