phase 2 – Page 5 – All About Drugs

AltheRx obtains US patent for solabegron combination therapy for OAB treatment

phase 2, Uncategorized Comments Off

Oct 212013

solabegron

AltheRx Pharmaceuticals has received a notice of allowance for its patent application from the US Patent and Trademark Office (USPTO) for the use of solabegron, a beta 3-adrenergic receptor agonist, in combination with antimuscarinics at both therapeutic and sub-therapeutic doses, for the treatment of overactive bladder (OAB).

AltheRx obtains US patent for solabegron combination therapy for OAB treatment

http://www.pharmaceutical-technology.com/news/newsaltherx-obtains-us-patent-for-solabegron-combination-therapy-for-oab-treatment?WT.mc_id=DN_News

Solabegron (GW-427,353) is a drug which acts as a selective agonist for the β3 adrenergic receptor. It is being developed for the treatment of overactive bladder andirritable bowel syndrome.^[1]^[2]^[3] It has been shown to produce visceral analgesia by releasing somatostatin from adipocytes.,^[4]^[5]

Solabegron was discovered by GlaxoSmithKline and acquired by AltheRx in March 2011. Solabegron relaxes the bladder smooth muscle by stimulating beta-3 adrenoceptors, a novel mechanism compared to older established drug treatments for overactive bladder syndrome such as the anticholinergic agents. Astellas Pharma have developed the first commercially available β3 adrenergic receptor, mirabegron, which is now licensed in Japan^[6] and the US^[7] for overactive bladder. Mirabegron is not licensed for irritable bowel syndrome.

A Phase II study of Solabegron for overactive bladder (OAB) looked at 258 patients with moderate to severe incontinence experiencing an average of 4.5 wet episodes per day. Results demonstrated a statistically significant improvement with Solabegron as compared to placebo, as measured by the percent reduction of the number of wet episodes and the absolute number of daily voids.

A Phase II study for irritable bowel syndrome (IBS) evaluated 102 patients with IBS. Solabegron demonstrated significant reduction in pain associated with the disorder and a trend for greater improvement in the quality of life, compared to placebo.

Both Phase II studies indicated a tolerability profile for Solabegron that was similar to placebo. The OAB patients did not suffer from dry mouth, constipation, increase in heart rate or cognitive issues.

AltheRx is currently preparing to advance Solabegron into a large clinical study in OAB.

Synthesis

Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP. GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog. Journal of Pharmacology and Experimental Therapeutics. 2007 Oct;323(1):202-9.doi:10.1124/jpet.107.125757 PMID 17626794
Grudell AB, Camilleri M, Jensen KL, Foxx-Orenstein AE, Burton DD, Ryks MD, Baxter KL, Cox DS, Dukes GE, Kelleher DL, Zinsmeister AR. Dose-response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health.American Journal of Physiology. Gastrointestinal and Liver Physiology. 2008 May;294(5):G1114-9. PMID 18372395
Kelleher DL, Hicks KJ, Cox DS, et al. Randomized, double-blind, placebo (PLA)-controlled, crossover study to evaluate efficacy and safety of the beta 3-adrenergic receptor agonist solabegron (SOL) in patients with irritable bowel syndrome (IBS). Neurogastroenterol Motil 2008;20 (Suppl 2):131.
Cellek S, Thangiah R, Bassil AK, Campbell CA, Gray KM, Stretton JL, Lalude O, Vivekanandan S, Wheeldon A, Winchester WJ, Sanger GJ, Schemann M, Lee K. Demonstration of functional neuronal beta3-adrenoceptors within the enteric nervous system. Gastroenterology. 2007 Jul;133(1):175-83.
Schemann M, Hafsi N, Michel K, Kober OI, Wollmann J, Li Q, Zeller F, Langer R, Lee K, Cellek S. The beta3-adrenoceptor agonist GW427353 (solabegron) decreases excitability of human enteric neurons via release of somatostatin.Gastroenterology 2009 Sep 25. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/22384458
http://chembl.blogspot.co.uk/2012/07/new-drug-approvals-2012-pt-xiv.html

Phase II trials of TB drug through open source drug discovery programme to begin soon

phase 2, Uncategorized Comments Off

Jul 222013

PA 824

The search for a new tuberculosis drug after many decades and first time through a unique model of open drug discovery programme may finally bear fruits in near future, with India all set for the launch of the phase II clinical trial of the drug candidate.

The drug, coming through the Open Source Drug Discovery (OSDD) programme by Council of Scientific and Industrial Research (CSIR), will go for the clinical trials on drug-resistant TB patients in India very soon. The process of filing for permission from the Drug Controller General of India (DCGI) is on and public sector LRS Hospital for Respiratory and Infectious Diseases, New Delhi, has been selected for trials. This phase II trials will involve around 250-300 patients, sources said.

The drug candidate, Pa824, was synthesised in India long ago. After a series of ownership changes, the molecule was licensed to CSIR for further development now.

http://www.pharmabiz.com/NewsDetails.aspx?aid=76568&sid=1

Tuberculosis (TB) is one of the leading infectious diseases in the world, with approximately one-third of the world’s population harboring the causative agent, Mycobacterium tuberculosis (Mtb). Though previously a disease associated with aristocratic societies, TB is now predominantly a third-world disease, particularly affecting Asian communities and sub-Saharan Africa. Mtb isolates are increasingly resistant to drug therapies: multidrug-resistant TB (MDR TB) or more severely, extensively drug-resistant TB (XDR TB). As a consequence of these emerging strains, it is becoming increasingly apparent that novel drugs are necessary to combat Mtb infections.

PA 824 is an experimental anti-tuberculosis drug.^[1]^[2] The bicyclic nitroimidazole like molecule PA-824 has got a very complex mechanism of action active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis.Microarray analysis of the mode of action of PA-824 showed a puzzling mixed effect both on genes responsive to both cell wall inhibition (like isoniazid) and respiratory poisoning (like cyanide). The aerobic killing mechanism of this drug appears to involve inhibition of cell wall mycolic acid biosynthesis through an as yet unknown molecular mechanism.The respiratory poisoning through nitric oxide release seemed to be a crucial element of anaerobic activity by PA-824. The effect of PA-824 on the respiratory complex under hypoxic non-replicating conditions was also manifested in a rapid drop in intracellular ATP levels, again similar to that observed by cyanide treatment.^[3]PA-824 recently was shown to be safe, well tolerated, and efficacious at doses of 100–200 mg daily in a dose-ranging study among drug-sensitive, sputum smear–positive, adult pulmonary TB patients ^[4]

Tuberculosis treatment#Treatment of MDR-TB
Delamanid, a related drug

Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK (September 2009). “Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects”. Antimicrob. Agents Chemother. 53 (9): 3720–5.doi:10.1128/AAC.00106-09. PMC 2737845. PMID 19528280.
Stover CK, Warrener P, VanDevanter DR, et al (2000). “A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis”. Nature 405 (6789): 962–6. doi:10.1038/35016103. PMID 10879539.
Manjunatha U, Boshoff IM Helena, Barry CE (May-Jun 2009). “The mechanism of action of PA-824”. Commun Integr Biol. 2 (3): 215–218. PMC 2717523.
http://www.pipelinereport.org/browse/tb-treatments/pa-824

QSAR modeling of the nitroimidazole PA-824. Shown are two hydrogen bond acceptors (green), one hydrogen bond donor (purple), and one hydrophobe (aqua). Credit: NIAID

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.

Gilead Sciences reported that in a recent Phase 2 study, its oral drug idelalisib successfully drove the life-threatening chronic lymphocytic leukemia (CLL) into remission.

phase 2 1 Response »

May 292013

3 Biopharma Runners With Fuel in the Tank
Investorplace.com
Gilead Sciences (GILD) stock recently set a new all-time high after reporting that in a recent Phase 2 study, its oral drug idelalisib successfully drove the life-threatening chronic lymphocytic leukemia (CLL) into remission. The regimen produced a 97% …

Gilead Sciences (GILD) stock recently set a new all-time high after reporting that in a recent Phase 2 study, its oral drug idelalisib successfully drove the life-threatening chronic lymphocytic leukemia (CLL) into remission. The regimen produced a 97% response rate, with 93% of trial patients surviving progression-free at the end of two years. CLL, which produces too many mature white cells, is the second most common form of leukemia in the U.S.