Phase 3 drug – Page 5 – All About Drugs

AstraZeneca began a pivotal trial with selumetinib , thyroid cancer, Phase 3 trial

Phase 3 drug, Uncategorized Comments Off

Jul 232013

selumetinib

Array Biopharma To Report Top-line Results From ARRY-502 Asthma Trial
Sacramento Bee
AstraZeneca began a pivotal trial with selumetinib (an Array-invented drug) in patients with thyroid cancer in May 2013 and expects to begin a Phase 3 trial in patients with non-small cell lung cancer during the second half of 2013. Three other Array …

http://www.sacbee.com/2013/07/22/5586413/array-biopharma-to-report-top.html

Selumetinib (AZD6244) is a drug being investigated for the treatment of various types of cancer, for example non-small cell lung cancer (NSCLC).

The gene BRAF is part of the MAPK/ERK pathway, a chain of proteins in cells that communicates input from growth factors. Activating mutations in the BRAF gene, primarily V600E (meaning that the amino acid valine in position 600 is replaced by glutamic acid), are associated with lower survival rates in patients with papillary thyroid cancer. Another type of mutation that leads to undue activation of this pathway occurs in the gene KRAS and is found in NSCLC. A possibility of reducing the activity of the MAPK/ERK pathway is to block the enzyme MAPK kinase (MEK), immediately downstream of BRAF, with the drug selumetinib. More specifically, selumetinib blocks the subtypes MEK1 and MEK2 of this enzyme.^[1]

In addition to thyroid cancer, BRAF-activating mutations are prevalent in melanoma (up to 59%), colorectal cancer (5–22%), serous ovarian cancer (up to 30%), and several other tumor types.^[2]

KRAS mutations appear in 20 to 30% of NSCLC cases and about 40% of colorectal cancer.^[1]

A Phase II clinical trial about selumetinib in NSCLC has been completed in September 2011;^[3] one about cancers with BRAF mutations is ongoing as of June 2012^[update].^[4]

Troiani, T.; Vecchione, L.; Martinelli, E.; Capasso, A.; Costantino, S.; Ciuffreda, L. P.; Morgillo, F.; Vitagliano, D. et al. (2012). “Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase a activation in human lung and colorectal cancer cells”. British Journal of Cancer 106 (10): 1648–1659. doi:10.1038/bjc.2012.129. PMC 3349172. PMID 22569000. |displayauthors= suggested (help) edit
Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H. et al. (2002). “Mutations of the BRAF gene in human cancer”. Nature 417 (6892): 949–954. doi:10.1038/nature00766. PMID 12068308. |displayauthors= suggested (help) edit
ClinicalTrials.gov NCT00890825 Comparison of AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive Non Small Cell Lung Cancer (NSCLC) Patients
ClinicalTrials.gov NCT00888134 AZD6244 in Cancers With BRAF Mutations

more info…………………………………….

AZD-6244 (Selumetinib) is an orally-available, aminobenzimidazole-based, allosteric inhibitor of MEK1 kinase with an IC50 of 14 nM. [1] IC50 concentrations of
In cellular growth assays, AZD-6244 was more potent in cell lines containing activating B-Raf and Ras mutations, with IC50 values ranging from 59 to 473 nM. In HT-29 and Malme-3M cell studies, AZD-6244 was found to induce G1-S cell cycle arrest, inducing apoptosis after a 2-day incubation period. [1] In Colo-205 xenografts, AZD6244 induced increased levels of cleaved caspase-3, indicating apoptosis. [2]

In diffuse large B-cell lymphoma (DLBCL) lines, nanomolar concentration of AZD-6244 effectively downregulated MEK/ERK target substrates, including c-Myc, Mcl-1, and Bcl-2. [3]

Technical information:

Chemical Formula:		C₁₇H₁₅BrClFN₄O₃
CAS #:		606143-52-6
Molecular Weight:		457.68

Appearance:		White
Chemical Name:		6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide
Solubility:		Up to 100 mM in DMSO
Synonyms:		AZD-6244, AZD 6244, AZD6244, Selumetinib, Selumetinib sulfate, NSC-748727, ARRY-142886

Reference:

1.	Yeh et al., Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin. Cancer Res. 2007, 13, 1576-1583 Pubmed ID: 17332304
2.	Davies et al., AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol. Cancer Ther. 2007, 6, 2209-2219. Pubmed ID: 17699718
3.	Bhalla et al., The novel anti-MEK small molecule AZD6244 induces BIM-dependent and AKT-independent apoptosis in diffuse large B-cell lymphoma. Blood, 2011, 118(4), 1052-1061. Pubmed ID: 21628402

Sarepta Therapeutics Announces At-the-Market Equity Offering Facility

Phase 3 drug Comments Off

Jul 042013

Sarepta Therapeutics Announces At-the-Market Equity Offering Facility
Wall Street Journal
… for general corporate purposes, including for manufacturing scale up for eteplirsen, the planned confirmatory Phase III clinical study of eteplirsen and early development activities related to follow-on Duchenne muscular dystrophy drugs and other …

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http://online.wsj.com/article/PR-CO-20130703-908304.html

Navidea starts clinical trial for Alzheimer’s diagnostic drug

Phase 3 drug Comments Off

Jun 282013

Navidea Biopharmaceuticals hopes to bring an early diagnostic drug for Alzheimer’s disease to market.

AZD4694, NAV4694 STRUCTURE

Navidea starts clinical trial for Alzheimer’s diagnostic drug
Business First of Columbus
The Phase 3 trial for the Alzheimer’s agent, at the moment named NAV4694, will compare how well the drug displays the buildup of a damaging protein in the brain of patients believed to have Alzheimer’s compared with what’s found in the autopsy. There …

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http://www.bizjournals.com/columbus/news/2013/06/27/navidea-starts-clinical-trial-for.html

http://jnm.snmjournals.org/content/54/6/880.abstract

Navidea Biopharmaceuticals, a Dublin, Ohio biopharmaceutical company focused on precision diagnostics, earlier this week announced the completion of a study of its novel radiopharmaceutical NAV4694 as a biomarker for Alzheimer’s disease (AD).

NAV4694 is designed to aid visual detection and quantification of cerebral beta amyloid in diagnosing Alzheimer’s disease (AD). One hallmark of AD is the accumulation of beta amyloid plaques between nerve cells in the brain.

The study was designed and conducted by Navidea’s partner, AstraZeneca, to assess the safety and of the biomarker during PET scanning in subjects with AD and in healthy volunteers. Efficacy measures included binding parameters and overall image quality. The 16-patient trial was completed at Karolinska Institutet sites in Stockholm, Sweden.

Phase III studies show linagliptin improved blood glucose control in Asian …

diabetes, Phase 3 drug 1 Response »

Jun 242013

LINAGLIPTIN

Phase III studies show linagliptin improved blood glucose control in Asian …
Wall Street Journal
RIDGEFIELD, Conn. and INDIANAPOLIS, June 22, 2013 /PRNewswire/ — Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company (NYSE: LLY) today announced results from two phase III clinical studies that showed linagliptin in Asian adults, as …

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http://online.wsj.com/article/PR-CO-20130622-901315.html

Amgen In Focus

companies, phase 1, phase 2, Phase 3 drug, Uncategorized 1 Response »

Jun 202013

Amgen In Focus
Seeking Alpha
According to Amgen, they have 45 drugs in development from Phase 1 to Phase 3. Conversely, Gilead has 32 drugs in development and Pfizer has 64. Meanwhile, Gilead only has 8 drugs in Phase 3, Pfizer has 25, and Amgen has 14. 7 of those Phase 3 …

http://seekingalpha.com/article/1510002-amgen-in-focus?source=google_news

Amgen has the second deepest pipeline of drugs of the three large cap biotechs. According to Amgen, they have 45 drugs in development from Phase 1 to Phase 3. Conversely, Gilead has 32 drugs in development and Pfizer has 64. Meanwhile, Gilead only has 8 drugs in Phase 3, Pfizer has 25, and Amgen has 14. 7 of those Phase 3 drugs are focused on cancer treatments for Amgen, more than either Pfizer or Gilead. Keep in mind that 12.4 million people learn they have cancer each year, while 7.6 million people lose that battle each year. The CDC predicts that the global number of cancer related deaths will increase by 80% by 2030. It doesn’t take a rocket scientist to know that cancer treating drugs presents the largest opportunity for any drug maker considering those statistics. Amgen has the inside track versus Gilead and Pfizer as far as quantity of drugs in late stage development.

Pipeline

This information is current as of February 11, 2013. Amgen’s product pipeline will change over time as molecules move through the drug development process, including progressing to market or failing in clinical trials, due to the nature of the development process. This description contains forward-looking statements that involve significant risks and uncertainties, including those discussed in Amgen’s most recent Form 10-K and in Amgen’s periodic reports on Form 10-Q and Form 8-K, and actual results may vary materially. Amgen is providing this information as of the date above and does not undertake any obligation to update any forward-looking statements contained in this table as a result of new information, future events or otherwise.

Phase 1

AMG 110

Various cancer types

AMG 110 is an anti-EpCAM (epithelial cell adhesion molecule) x anti-CD3 (BiTE®) bispecific antibody. It is being investigated as a cancer treatment.

AMG 139

Inflammatory diseases

AMG 139 is a human monoclonal antibody. It is being investigated as a treatment for Crohn’s disease. AMG 139 is being jointly developed in collaboration with AstraZeneca.

AMG 157

Asthma

AMG 157 is a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP). It is being investigated as a treatment for asthma. AMG 157 is being jointly developed in collaboration with AstraZeneca.

AMG 167

Bone-related conditions

AMG 167 is a humanized monoclonal antibody that inhibits the action of sclerostin. AMG 167 is being developed in collaboration with UCB for bone-related conditions.

Other
Modality

AMG 172

Various cancer types

AMG 172 is a human anti-CD27L antibody drug conjugate. It is being investigated as a cancer treatment.

AMG 208

Various cancer types

AMG 208 is a small molecule inhibitor of MET. It is being investigated as a cancer treatment.

AMG 232

Various cancer types

AMG 232 is a small molecule. It is being investigated as a cancer treatment.

AMG 319

Hematologic malignancies

AMG 319 is a small molecule inhibitor of PI3 Kinase delta. It is being investigated as a cancer treatment.

AMG 334

Migraine

AMG 334 is a human monoclonal antibody that inhibits the receptor for Calcitonin Gene-Related Peptide (CGRP). It is being investigated for the prevention of migraine.

AMG 337

Various cancer types

AMG 337 is a small molecule inhibitor of MET. It is being investigated as a cancer treatment.

AMG 357

Autoimmune diseases

AMG 357 is a small molecule. It is being investigated as a treatment for autoimmune diseases.

AMG 557

Systemic lupus erythematosus

AMG 557 is a human monoclonal antibody that inhibits the action of B7 related protein (B7RP-1). It is being investigated as a treatment for systemic lupus erythematosus. AMG 557 is being jointly developed in collaboration with AstraZeneca.

Other
Modality

AMG 595

Glioblastoma

AMG 595 is a human anti-EGFRvIII (epidermal growth factor receptor) antibody drug conjugate. It is being investigated as a treatment for glioblastoma.

AMG 729

Autoimmune diseases

AMG 729 is a humanized monoclonal antibody that targets CD19 and CD32b to inhibit B cell. It is being investigated as a treatment for systemic lupus erythematosus and rheumatoid arthritis.

AMG 780

Various cancer types

AMG 780 is a human anti-angiopoietin antibody that inhibits the interaction between the endothelial cell-selective Tie2 receptor and its ligands Ang1 and Ang2. It is being investigated as a cancer treatment.

AMG 811

Systemic lupus erythematosus

AMG 811 is a human monoclonal antibody that inhibits interferon gamma. It is being investigated as a treatment for systemic lupus erythematosus.

AMG 820

Various cancer types

AMG 820 is a human monoclonal antibody that inhibits c-fms and decreases tumor associated macrophage (TAM) function. It is being investigated as a cancer treatment.

AMG 876

Type 2 diabetes

AMG 876 is a fusion protein. It is being investigated as a treatment for type 2 diabetes.

AMG 900

Various cancer types

AMG 900 is a small molecule inhibitor of Aurora kinases A, B, and C. It is being investigated as a cancer treatment.

Phase 2

AMG 151

Type 2 diabetes

AMG 151 is a small molecule glucokinase activator. It is being investigated as a treatment for type 2 diabetes.

AMG 181

Inflammatory bowel disease

AMG 181 is a human monoclonal antibody that inhibits the action of alpha4/beta7. It is being investigated as a treatment for ulcerative colitis and Crohn’s disease. AMG 181 is being jointly developed in collaboration with AstraZeneca.

Other
Modality

AMG 416

Secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis

AMG 416 is a peptide agonist of the human cell surface calcium-sensing receptor (CaSR). It is being investigated as a treatment for secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis.

AMG 747

Schizophrenia

AMG 747 is a small molecule inhibitor of glycine transporter type-1 (GlyT-1). It is being investigated as a treatment for negative symptoms and cognitive deficits associated with schizophrenia.

Blinatumomab
(AMG 103)

Acute lymphoblastic leukemia

Blinatumumab is an anti-CD19 x anti-CD3 (BiTE®) bispecific antibody. It is being investigated as a cancer treatment.

Blinatumomab
(AMG 103)

Non-Hodgkin’s Lymphoma

Blinatumumab is an anti-CD19 x anti-CD3 (BiTE®) bispecific antibody. It is being investigated as a cancer treatment.

Brodalumab
(AMG 827)

Inflammatory diseases

Brodalumab is a human monoclonal antibody that inhibits the interleukin-17 receptor. It is being investigated as a treatment for a variety of inflammatory diseases. Brodalumab is being jointly developed in collaboration with AstraZeneca.

Omecamtiv mecarbil

Heart failure

Omecamtiv mecarbil is a small molecule activator of cardiac myosin. It is being investigated for the treatment of heart failure. We are developing this product in collaboration with Cytokinetics, Inc.

Prolia® (denosumab)

Rheumatoid arthritis

Denosumab is a human monoclonal antibody that specifically targets a ligand known as RANKL (that binds to a receptor known as RANK) which is a key mediator of osteoclast formation, function, and survival. It is being investigated across a range of conditions including osteoporosis, treatment-induced bone loss, rheumatoid arthritis and numerous tumor types across the spectrum of cancer-related bone diseases, including hypercalcemia of malignancy.

Trebananib
(AMG 386)

Various cancer types

Trebananib is a peptibody that inhibits the interaction between the endothelial cell-selective Tie2 receptor and its ligands Ang1 and Ang2. It is being investigated as a cancer treatment.

Vectibix® (panitumumab)

Squamous cell head and neck cancer

Vectibix® is a human monoclonal antibody antagonist of the epidermal growth factor receptor (EGFr) pathway. It is being investigated as a cancer treatment.

XGEVA® (denosumab)

Giant cell tumor of the bone

XGEVA® (denosumab)

Hypercalcemia of malignancy

Phase 3

AMG 145

Hyperlipidemia

AMG 145 is a human monoclonal antibody that inhibits Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). It is being investigated as a treatment for hyperlipidemia.

Aranesp® (darbepoetin alfa)

Myelodysplastic syndromes

Aranesp® is a recombinant human protein agonist of the erythropoietin receptor.

Brodalumab
(AMG 827)

Psoriasis

Prolia® (denosumab)

Glucocorticoid-induced osteoporosis

Prolia® (denosumab)

Male osteoporosis (EU)

Rilotumumab

Gastric cancer

Rilotumumab is a human monoclonal antibody that inhibits the action of hepatocyte growth factor/scatter factor. It is being investigated as a cancer treatment.

Romosozumab
(AMG 785)

Postmenopausal osteoporosis

Romosozumab is a humanized monoclonal antibody that inhibits the action of sclerostin. It is being developed in collaboration with UCB for the treatment of postmenopausal osteoporosis.

Sensipar®/ Mimpara® (cinacalcet)

Post renal transplant

Sensipar®/Mimpara® is an orally-administered small molecule that lowers parathyroid hormone (PTH) levels in blood by increasing sensitivity of the calcium-sensing receptor (CaSR) to extracellular calcium. It is being evaluated in post renal transplant patients.

Talimogene laherparepvec

Melanoma

Talimogene laherparepvec is an oncolytic immunotherapy derived from HSV-1. It is being investigated as a cancer treatment.

Trebananib
(AMG 386)

Ovarian cancer

Trebananib is a peptibody that inhibits the interaction between the endothelial cell-selective Tie2 receptor and its ligands Ang1 and Ang2. It is being investigated as a cancer treatment.

Vectibix® (panitumumab)

First- and second-line colorectal cancer (U.S.)

Vectibix® is a human monoclonal antibody antagonist of the epidermal growth factor receptor (EGFr) pathway. It is being investigated as a cancer treatment.

XGEVA® (denosumab)

Cancer-related bone damage (skeletal-related events) in patients with multiple myeloma

XGEVA® (denosumab)

Delay or prevention of bone metastases in breast cancer

XGEVA® (denosumab)

Delay or prevention of bone metastases in prostate cancer (EU)

Phase 1 clinical trials investigate safety and proper dose ranges of a product candidate in a small number of human subjects.Phase 2 clinical trials investigate side effect profiles and efficacy of a product candidate in a large number of patients who have the disease or condition under study.Phase 3 clinical trials investigate the safety and efficacy of a product candidate in a large number of patients who have the disease or condition under study.

ViroPharma Receives Orphan Drug Designation For Maribavir In Europe

drugs, Phase 3 drug Comments Off

Jun 122013

Maribavir

ViroPharma Receives Orphan Drug Designation For Maribavir In Europe
The Herald | HeraldOnline.com
We commend the European Commission for providing incentives such as this for the development of drugs for rare and life threatening diseases.” ViroPharma is currently conducting two Phase 2 dose ranging studies of oral maribavir at one of three doses …

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http://www.heraldonline.com/2013/06/11/4934867/viropharma-receives-orphan-drug.html

Maribavir (originally named 1263W94) is an experimental oral antiviral drug candidate licensed by ViroPharma from GlaxoSmithKline in 2003 for the prevention and treatment of human cytomegalovirus (HCMV) disease in hematopoietic stem cell/bone marrow transplant patients. The mechanism by which maribavir inhibits HCMV replication is by inhibition of an HCMV encoded protein kinase enzyme called UL97 or pUL97. Maribavir showed promise in Phase II clinical trials and was granted fast track status, but failed to meet study goals in a Phase III trial. However, the dosage used in the Phase III trial may have been too low to be efficacious.

A Phase II study with maribavir demonstrated that prophylaxis with maribavir displayed strong antiviral activity, as measured by statistically significant reduction in the rate of reactivation of CMV in recipients of hematopoietic stem cell/bone marrow transplants. In an intent-to-treat analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced with maribavir compared to placebo.

ViroPharma conducted a Phase III clinical study to evaluate the prophylactic use for the prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplant patients. In February 2009, ViroPharma announced that the Phase III study failed to achieve its goal, showing no significant difference between maribavir and a placebo at reducing the rate at which CMV DNA levels were detected in patients.

Bristol Myers Squibb Co.present data on its Phase 3 drug nivolumab, which is closest to reaching the market. (Its FDA approval is expected in late 2014 or early 2015.)

Phase 3 drug Comments Off

May 292013

Bristol Myers Squibb Co. (BMY), Gilead Sciences, Inc. (GILD), Halozyme …
Insider Monkey (blog)
present data on its Phase 3 drug nivolumab, which is closest to reaching the market. (Its FDA approval is expected in late 2014 or early 2015.) Nivolumab has the potential to treat a vast array of cancers. At ASCO, Bristol Myers Squibb Co.

http://www.insidermonkey.com/blog/bristol-myers-squibb-co-bmy-gilead-sciences-inc-gild-halozyme-therapeutics-inc-halo-3-stocks-to-watch-ahead-of-asco-152583/

Bristol Myers Squibb Co. (NYSE:BMY) present data on its Phase 3 drug nivolumab, which is closest to reaching the market. (Its FDA approval is expected in late 2014 or early 2015.)

Nivolumab has the potential to treat a vast array of cancers. At ASCO, Bristol Myers Squibb Co. (NYSE:BMY) will be presenting data for a Phase 1 study of nivolumad combined with Yervoy to treat melanoma. In a 52-patient study, patients with advanced melanoma saw an overall tumor shrinkage rate of 40%.

However, the company’s most advanced study with nivolumab is in treating advanced non-small cell lung cancer. There, it produced an overall survival of 9.6 months, which is 30% better than standard-of-care. It’s also produced a 22-month overall survival rate in patients with advanced kidney cancer; compared to 20 months for the current standard of care

Merck Provides Update on Phase III Clinical Program for Preladenant, the Company’s Investigational Parkinson’s Disease Medicine

Phase 3 drug, Uncategorized Comments Off

May 262013

PREDADENANT

Links

http://newdrugapprovals.wordpress.com/2013/05/26/merck-provides-update-on-phase-iii-clinical-program-for-preladenant-the-companys-investigational-parkinsons-disease-medicine/

Novo Nordisk Says Will Seek Approval of Obesity Drug Liraglutide Next Year

Phase 3 drug Comments Off

May 252013

liraglutide

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http://www.pharmalive.com/novo-nordisk-says-will-seek-approval-of-obesity-drug-next-year

Systematic (IUPAC) name

L-histidyl-L-alanyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-valyl-L-seryl-L-seryl-L-tyrosyl-L-leucyl-L-α-glutamylglycyl-L-glutaminyl-L-alanyl-L-alanyl-N⁶-[N-(1-oxohexadecyl)-L-γ-glutamyl]-L-lysyl-L-α-glutamyl-L-phenylalanyl-L-isoleucyl-L-alanyl-L-tryptophyl-L-leucyl-L-valyl-L-arginylglycyl-L-arginyl-glycine

Liraglutide (NN2211), marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 agonist (GLP-1 agonist) developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency (EMA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.

Liraglutide is marketed under the brandname Victoza in the U.S., India, Canada, Europe and Japan. It has been launched in Germany, Denmark, the Netherlands, the United Kingdom, Ireland, Sweden, Japan, Canada, the United States, France, Malaysia and Singapore.

Phase I trials of an oral variant of Victoza (NN9924) started in 2010.