Alexion’s Soliris® (eculizumab) Receives Orphan Drug Designation for the Treatment of Neuromyelitis Optica (NMO)

Structure of eculizumab. Eculizumab was engineered to reduce immunogenicity and eliminate effector function. Human IgG2 and IgG4 heavy-chain sequences were combined to form a hybrid constant region that is unable to bind Fc receptors or to activate the complement cascade. Eculizumab exhibits high affinity for human C5, effectively blocking its cleavage and downstream proinflammatory and cell lytic properties. Reprinted from Rother et al with permission.  

Alexion's Soliris® (eculizumab) Receives Orphan Drug Designation for the ...

Fort Mills Times
In a Phase 2 study presented at the 2012 annual meeting of the American Neurological Association (ANA), Soliris treatment was associated with a significant reduction in the frequency of relapses (recurring attacks) in patients with severe, relapsing ...

http://www.fortmilltimes.com/2013/06/27/2789656/alexions-soliris-eculizumab-receives.html


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). It costs £400,000 (US$600,000) per year per patient

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.

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.Clinical trials in patients with aHUS demonstrated inhibition of thrombotic microangiopathy (TMA),the formation of blood clots in small blood vessels throughout the body, including normalization of platelets and lactate dehydrogenase (LDH), as well as maintenance or improvement in renal function.

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.

Celgene buys MophoSys for myeloma antibody development

Celgene buys MophoSys for myeloma antibody development
German biopharmaceutical company MorphoSys will jointly develop an antibody for the treatment of multiple myeloma (MM) and leukaemia with Celgene Corporation. 

http://www.pharmaceutical-technology.com/news/newscelegene-buys-mophosys-for-myeloma-antibody-development?WT.mc_id=DN_News

Novartis' Omalizumab Meets Phase III Endpoints

Novartis' Omalizumab Meets Phase II...

Novartis reports new Phase III data showing omalizumab significantly...



http://www.pharmalive.com/novartis-omalizumab-meets-phase-iii-endpoints

Structures of resistance-breaking derivatives of established antibiotic classes. Selected compounds are depicted that were recently launched or are currently in development. Ceftobiprole has increased affinity for PBP2a, a member of the target family of penicillin-binding proteins not affected by marketed β-lactams. Tigecycline, iclaprim, telithromycin, and telavancin make contacts to additional binding sites on their established targets or address additional targets. Structural elements responsible for the novel target interactions are marked bold. MCB-3681, TD-1792, and CBR-2092 are hybrid molecules, in which two pharmacophors from different antibiotic classes are attached by linkers. Linkers are marked bold

All antibiotics that have been successfully employed for decades as monotherapeutics in the treatment of bacterial infections rely on mechanisms of bacterial growth inhibition which are by far more complex than inhibition of a single enzyme. Such successful antibiotics have in common that they address several targets in parallel and/or that their targets are encoded by multiple genes. Such multiplicity of targets and of target genes has the advantage that the emergence of spontaneous target-related resistance is a comparatively slow process. Recently registered antibiotics and novel antibiotics in development are discussed in the light of this promising concept of antibacterial polypharmacology.

How many modes of action should an antibiotic have?

• Heike Brötz-Oesterhelt 
• Nina A Brunner 

• AiCuris GmbH & Co.KG, Friedrich-Ebert Strasse 475, Building 302, D-42117 Wuppertal, Germany

Available online 30 July 2008

• http://dx.doi.org/10.1016/j.coph.2008.06.008,

http://www.sciencedirect.com/science/article/pii/S1471489208000799

Preventing Dangerous Liaisons

A new peptidomimetic inhibits prostate cancer’s growth by preventing the androgen receptor from binding to its cofactor
Read more

http://www.chemistryviews.org/details/news/4884471/Preventing_Dangerous_Liaisons.html

A combination of the myxoma virus and the immune suppressant rapamycin can kill glioblastoma multiforme, the most common and deadliest malignant brain tumor

 read all at

http://www.dddmag.com/news/2013/06/virotherapy-rapamycin-combo-kills-brain-tumors

rapamycin, sirolimus

.Artificial sweetener a potential treatment for Parkinson’s disease.

Mannitol, a sugar alcohol produced by fungi, bacteria, and algae, is a common component of sugar-free gum and candy. The sweetener is also used in the medical field — it’s approved by the FDA as a diuretic to flush out excess fluids and used during surgery as a substance that opens the blood/brain barrier to ease the passage of other drugs.

Now Profs. Ehud Gazit and Daniel Segal of Tel Aviv University‘s Department of Molecular Microbiology and Biotechnology and the Sagol School of Neuroscience, along with their colleague Dr. Ronit Shaltiel-Karyo and PhD candidate Moran Frenkel-Pinter, have found that mannitol also prevents clumps of the protein α-synuclein from forming in the brain — a process that is characteristic of Parkinson’s disease.

Read more at

http://scienceblog.com/63913/artificial-sweetener-a-potential-treatment-for-parkinsons-disease/

Ambrx partners with Zhejiang for breast cancer antibody drug conjugate development

Ambrx has partnered with Zhejiang Medicine for the development and commercialization of ARX788, its antibody drug conjugate (ADC) for breast cancer... Targeting Her2-positive breast cancer, ARX788 is developed by the clinical stage biopharmaceutical company Ambrx as site-specific ADC.

http://contractresearch.pharmaceutical-business-review.com/news/ambrx-partners-with-zhejiang-for-breast-cancer-antibody-drug-conjugate-development-170613

HANDBOOK OF MEDICINAL HERBS-by DOCSTOC

Handbook of Medicinal Herbs (PDF)

INDA

Investigational new drug application from Gaurav Kr

Incyte Drug Jakafi ® (ruxolitinib) Improved Overall Survival in Phase III Trial of Patients with Myelofibrosis

ruxolitinib Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase ... Incyte Drug Jakafi®ruxolitinib Improved Overall Survival in Phase III Trial of Patients with Myel. by Business Wirevia The Motley Fool Jun 16th 2013 220AM ... http://www.dailyfinance.com/2013/06/16/incyte-drug-jakafi-ruxolitinib-improved-overall-su/ Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of bone marrow cancer. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, and for plaque psoriasis. The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size, relieving debilitating symptoms, and improving overall survival

Ibrutinib Phase 2 Data: Analyses Show Efficacy with Ibrutinib Monotherapy in Patients with Relapsed or Refractory Mantle Cell or Diffuse Large B-cell Lymphoma

ibrutinib

June 16, 2013 

Janssen Research & Development, LLC (Janssen), today announced the results of two separate Phase 2 studies suggesting that ibrutinib, an investigational oral Bruton's tyrosine kinase (BTK) inhibitor, shows efficacy when used as a monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL) or diffuse large B-cell lymphoma (DLBCL). The studies were presented today at the European Hematology Association (EHA) 18^th Annual Congress in Stockholm, Sweden. Ibrutinib is being jointly developed by Janssen and Pharmacyclics, Inc.

Ibrutinib (USAN), also known as PCI-32765, is an experimental drug candidate for the treatment of various types of cancer. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton tyrosine kinase (Btk).

Ibrutinib is currently under development by Pharmacyclics, Inc and Johnson & Johnson's Janssen Pharmaceutical division for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and multiple myeloma.

Ibrutinib was first designed and synthesized at Celera Genomics by Zhengying Pan, who along with a team of chemists and biologists reported in 2007 a structure-based approach for creating a series of small molecules that inactivate BTK through covalent binding to cysteine-481 near the ATP binding domain of BTK[2]. 

These small molecules irreversibly inhibited BTK by using a Michael acceptor for binding to the target cysteine. 

In April 2006, Pharmacyclics acquired Celera’s small molecule BTK inhibitor discovery program, which included a compound, PCI-32765 (known as compound 13 in the Pan et al paper) that was subsequently chosen for further preclinical development based on the discovery of anti-lymphoma properties in vivo . 

Since 2006, Pharmacyclics’ scientists have advanced the molecule into clinical trials and identified specific clinical indications for the drug.  It also has potential effects against autoimmune arthritis.

Pharma-Execs-2012-Pipeline-Report

 
Just days before this article went to press, FDA approved the first of a new kind of oral enzyme treatment that mediates cellular response, Incyte/Novartis' Jakafi, for a rare bone marrow disease called myelofibrosis. The next JAK inhibitor, Pfizer's toficitinib, could hit the market late next year, meaning a lot of rheumatoid arthritis patients will never again have to sit in a hospital for a couple of hours to get an anti-TNF infusion. Many innovative drugs, long out of the gate, are closing in on the finish line; science is back, and a better understanding of the way genomics shapes disease is bringing about better outcomes, and sometimes faster approvals.

read all at

http://www.pharmexec.com/pharmexec/Deals/Pharm-Execs-2012-Pipeline-Report/ArticleStandard/Article/detail/752361?contextCategoryId=48159

Amgen, Cytokinetics expand collaboration

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil

Omecamtiv mecarbil
Amgen, Cytokinetics expand collaboration

Thursday, June 13, 2013 01:30 PM

Amgen and Cytokinetics, a clinical-stage biopharmaceutical company, have expanded their strategic collaboration to include Japan. In 2006, Cytokinetics and Amgen entered into a collaboration to discover, develop and commercialize novel small-molecule therapeutics that activate cardiac muscle contractility for potential applications in the treatment of heart failure. Omecamtiv mecarbil is the most advanced drug candidate in this collaboration.

- See more at:
 http://www.centerwatch.com//news-online/article/4852/amgen-cytokinetics-expand-collaboration

 Omecamtiv mecarbil , previously codenamed CK-1827452, is a cardiac specific myosin activator. It is clinically tested for its role in the treatment of left ventricular systolic heart failure. Systolic heart failure is characterised as a decreased cardiac output (<40% ejection fraction), due to decreased stroke volume, resulting in the inability to meet the metabolic demands of the body. The loss of contraction is caused by a reduced number of effective actin-myosin cross bridges in the left ventricular myocytes. One possible underlying mechanism is altered signal transduction that interferes with excitation-contraction coupling. A decreased cardiac output causes peripheral hypotension and activation of the sympathetic nervous system. This in turn stimulates the cardiac myocytes excessively, eventually leading to left ventricular hypertrophy, characteristic of chronic heart failure. Some symptoms of systolic heart failure are fatigue, peripheral oedema, dyspnoea, exercise intolerance and breathlessness. Current inotropic drug therapies such as dobutamine, are palliative and not a cure. They also cause many adverse effects including arrhythmias related to increased myocardical oxygen consumption, desensitization of adrenergic receptors and altering intracellular calcium levels. Thus systolic heart failure is considered malignant, however the novel mechanism of Omecamtiv Mecarbil is a hopeful long-term resolution.

90Y-Epratuzumab Study Shows Improvement of Therapy Results Following R-CHOP

 


June 10, 2013 (GLOBE NEWSWIRE) -- Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today reported that adding two doses of epratuzumab labeled with the radioisotope, yttrium-90 (90Y), to a combination of rituximab and CHOP chemotherapy (R-CHOP), the standard of care for patients with diffuse large B-cell lymphoma (DLBCL), appeared to improve elderly patients' responses to treatment.

read all at
http://www.drugs.com/clinical_trials/90y-epratuzumab-study-shows-improvement-therapy-results-following-r-chop-15714.html 




by
WORLD DRUG TRACKER
DR ANTHONY

5 Signs You’ll Get Cancer

 

read all at

http://www.newsmaxhealth.com/MKTNews/Brownstein-cancer-video-documentary/2013/02/11/id/489887?promo_code=13945-1


by Dr Anthony

Regeneron, Bayer Report Positive Phase 3 Results for Eylea

 

Regeneron and Bayer Report Positive Phase 3 Results for EYLEA® (aflibercept) Injection in Myopic Choroidal Neovascularization (mCNV)

TARRYTOWN, N.Y., June 06, 2013 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Bayer HealthCare today announced positive top-line results for EYLEA® (aflibercept) Injection from the Phase 3 MYRROR study in myopic choroidal neovascularization (mCNV).

http://www.pharmalive.com/regeneron-bayer-report-positive-phase-3-results-for-eylea

 

Aflibercept is a fusion protein approved in the United States for the treatment of wet macular degeneration and metastatic colorectal cancer.

It is an inhibitor of vascular endothelial growth factor. It is designed to bind to VEGF-A,VEGF-B, and placental growth factor (a.k.a PIGF, gene symbol PGF).^[3]

Aflibercept is being co-developed by Sanofi-Aventis and Regeneron Pharmaceuticals.

 

Eculizumab proves effective in treating atypical hemolytic uremic syndrome

ECULIZUMAB


A new treatment for patients with atypical hemolytic uremic syndrome ( aHUS) was tested by researchers at Emory University. According to an article published in the New England Journal of Medicine, it seems that eculizumab, a monoclonal antibody, is effective in the management of this life-threatening inflammatory disease.
 
Hemolytic uremic syndrome, which is a thrombotic microangiopathy that causes blood clots in small vessels, is characterized by thrombocytopenia, hemolytic anemia and uremia. It mostly affects children up to 7 years old and is the most common cause of acute renal failure in children. The hemolytic uremic syndrome is often associated with enteric infections (E. coli, Shigella, Salmonella, etc.), but it can occur in other situations such as after certain drugs, tumors, after transplantation, etc..

Read more: http://www.doctortipster.com/14800-eculizumab-proves-effective-in-treating-atypical-hemolytic-uremic-syndrome.html















Site of action of eculizumab. a Complement C5 is split by C5 convertase into C5a and C5b. C5a increases the permeability of blood vessels and attracts inflammatory cells by chemotaxis. C5b binds to other complement components (C6, C7, and C8). The C5b-8 complex is expanded with C9 to form the MAC. MAC binds and permeabilizes bacterial walls (e.g. Neisseria), thereby killing the microorganism. b Eculizumab is a long-acting humanized monoclonal antibody targeted against complement C5. It inhibits the cleavage of C5 into C5a and C5b and hence inhibits deployment of the terminal complement system including the formation of MAC
 

DRUGS-Using FTIR and NIR spectroscopy in process control

http://www.manufacturingchemist.com/technical/article_page/Using_FTIR_and_NIR_spectroscopy_in_process_control/88634




BY WORLD DRUG TRACKER
DR ANTHONY CRASTO

Improving Compound Extraction Efficiency Novel Method for Skin Tissues Allows Higher-Throughput Sample Processing

READ ALL AT
http://www.genengnews.com/gen-articles/improving-compound-extraction-efficiency/4888/





BY WORLD DRUG TRACKER
DR ANTHONY CRASTO