Drug Combo Tackling Solid Tumors

Cancer Research UK's Drug Development Office has opened the first trial of a new drug combination in patients with advanced solid tumors and in a subset of patients who have non-small cell lung cancer. This trial will combine two compounds that aim to starve the tumors while simultaneously blocking cancer cell growth.

The study will take place across three UK hospitals. The Churchill Hospital, Oxford is the lead center. The trial of up to 48 patients will run in two stages. In the first stage patients with any solid tumor will each receive a drug called vandetanib (below left) and an investigational drug called selumetinib (right structure below)AZD6244, ARRY142886). In the second stage patients with non-small cell lung cancer (NSCLC) will receive the combination.

This is the first time the compounds have been trialled together. It is hoped that combining these treatments will increase the number of cancer ‘weakspots’ targeted at the same time.

Chief investigator, Dr. Denis Talbot, consultant medical oncologist at Oxford University Hospitals NHS Trust and Cancer Research UK clinician at The University of Oxford, said: “Therapies for lung cancer often become ineffective because the disease becomes resistant to treatment, so we’re delighted to launch this trial to test a new approach that we hope will help people with this common disease.

“There is progress being made in the treatment of lung cancer but survival rates still remain low. This is because the majority of patients – up to two thirds – are diagnosed once the cancer has already spread to other organs when it’s more difficult to treat successfully.

 “We hope that this new approach may eventually contribute to increased survival for lung cancer patients.”

Ref : http://cancerhelp.cancerresearchuk.org/trials/a-trial-of-vandetanib-and-selumetinib-for-solid-tumours-including-nsclc-vansel-1

Takeda announces updated results from orteronel phase 2 study on nmCRPC

Takeda announces updated results from orteronel phase 2 study on nmCRPC: Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited today announced updated results from a phase 2 study of orteronel, a selective oral 17,20 lyase inhibitor, dosed without prednisone in patients with non-metastatic castration resistant prostate cancer (nmCRPC) and rising prostate-specific antigen.

Ref : http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1702187&highlight=

Antisense Pharma presents data from trabedersen Phase I/II cancer study at ASCO 2012

In continuation of my update on antisense drugs

Trabedersen, is an antisense compound that specifically inhibits expression of transforming growth factor beta 2 (TGF-β2) – a protein which is overexpressed in advanced tumors and which triggers key cancer pathomechanisms, i.e. suppression of antitumor immune response and metastasis. 

Antisense Pharma presents data from trabedersen Phase I/II cancer study at ASCO 2012: The biopharmaceutical company Antisense Pharma today presents trabedersen complete data from its clinical Phase I/II study in patients with advanced pancreatic cancer, malignant melanoma or colorectal cancer at the international cancer congress ASCO 2012 in Chicago, USA.

Ancient berry could protect against diabetic retinopathy

In continuation of my update on wolfberry

Ancient berry could protect against diabetic retinopathy: The ancient Tibetan goji berry could help fight blindness caused by long-term diabetes according to studies conducted by University of Sydney researchers.

Dapivirine Phase III trial now underway in Africa to treat HIV in women

Dapivirine Phase III trial now underway in Africa to treat HIV in women

Investigational diabetes drug appears to improve insulin sensitivity without side effects

Drugs for type 2 diabetes can contribute to weight gain, bone fractures and cardiovascular problems, but in mice, an investigational drug appears to improve insulin sensitivity without those troublesome side effects, researchers at Washington University School of Medicine in St. Louis have shown.

"Current diabetes medications activate a receptor that improves insulin sensitivity, but unfortunately also contributes to side effects that make some people discontinue the medication, contributing to other health problems," says principal investigator Brian N. Finck, PhD. "So even though these drugs are effective, we'd really like to find new insulin-sensitizing therapies that would avoid activating the same receptor."

Finck, a research assistant professor of medicine in the Division of Geriatrics and Nutritional Science, worked with colleagues at the University of Michigan and at the drug discovery company Metabolic Solutions Development Co., LLC. The scientists studied one of the company's investigational drugs, MSD-0602, focusing on its effects in obese mice.

The drug improved blood glucose levels and insulin tolerance in the mice, as did the two diabetes drugs that already are on the market: rosiglitazone (Avandia) and pioglitazone (Actos). All three medications appeared to be about equally effective, but MSD-0602 didn't bind to and activate a receptor in cells called PPARγ. Rather, the investigational drug clings to the mitochondria, part of the cell that produces energy.

"The drug altered the cell's ability to generate energy," Finck says. "And it also seems to have an anti-inflammatory role in the cell. We also found that the drug improved insulin sensitivity in many different kinds of cells including muscle, fat and liver cells."

 Next, he and his colleagues will attempt to identify proteins that bind to the mitochondrial membrane. Future therapies then could be developed specifically to bind to those proteins while avoiding activation of the PPARγ pathway.

Investigational diabetes drug appears to improve insulin sensitivity without side effects: Drugs for type 2 diabetes can contribute to weight gain, bone fractures and cardiovascular problems, but in mice, an investigational drug appears to improve insulin sensitivity without those troublesome side effects, researchers at Washington University School of Medicine in St. Louis have shown.

Ref : http://www.jbc.org/content/early/2012/05/23/jbc.M112.363960.full.pdf

Cyclacel Presents New Phase 2 Data of Sapacitabine for MDS

We know that, Sapacitabine is an oral nucleoside analog prodrug that acts through a dual mechanism. The compound interferes with DNA synthesis by causing single-strand DNA breaks and induces arrest of the cell division cycle at G2 phase. Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in both blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (Gemzar; Lilly) or 5-FU, two widely used nucleoside analogs, in delaying the onset and growth of liver metastasis.

Cyclacel has initiated a number of clinical trials to evaluate sapacitabine in both solid and hematological tumors laying the foundation for future Phase 2 studies and combination studies with other anti-cancer agents. Three Phase 1 studies have been completed, which evaluated safety and pharmacokinetics of a variety of dosing schedules in approximately 120 patients with solid tumors. Sapacitabine is currently being evaluated in two Phase 2 trials in patients with advanced cutaneous T-cell lymphoma (CTCL) and in elderly patients with acute myeloid leukemias (AML).

Now Cyclacel Pharmaceuticals, Inc. announced new data from an ongoing, multicenter, Phase 2 randomized trial of oral sapacitabine capsules in older patients with myelodysplastic syndromes (MDS) after treatment failure of front-line hypomethylating agents, such as azacitidine or decitabine.

For advanced prostate cancer, new drug slows disease

In continuation of my update on abiraterone

The study is the first randomized clinical trial to document expanded benefits among a particular group of prostate cancer patients in whom the disease had spread. The medication, abiraterone acetate -- marketed as Zytiga -- also delayed the development of pain and deterioration of the patients' overall condition.

The researchers say the medication could provide new treatment options.

"This drug extended lives and gave patients more time when they weren't experiencing significant pain from the disease,'' said the principal.....

For advanced prostate cancer, new drug slows disease

RA Study Misses Primary Endpoint (CH-4051)...

In continuation of my update on CH-4051

Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) announced that a preliminary analysis of its dose-ranging exploratory Phase II trial of CH-4051, a non-metabolized antifolate, in patients with rheumatoid arthritis (RA) who experience an inadequate response to methotrexate (MTX) treatment indicates that CH-4051 did not demonstrate superior efficacy to methotrexate in the dose range evaluated.

"Results of this study provide evidence of the clinical activity of CH-4051, in a dose dependent manner, across multiple RA assessment criteria," commented Dr. Simon Pedder, president and CEO of Chelsea Therapeutics. "However, the outcome of the trial was confounded by the unexpectedly robust response reported by patients treated with methotrexate. While we believe that higher doses of CH-4051 could provide enhanced therapeutic benefit in RA and that CH-4051 could be developed for other anti-inflammatory and autoimmune indications, we believe our current resources would be better allocated toward the planned completion of our Northera™ (droxidopa) development program in neurogenic orthostatic hypotension. Consequently, we have no immediate plans to continue development of CH-4051."

Thioridazine drug successfully kills human cancer stem cells

Thioridazine drug successfully kills human cancer stem cells: A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.....

Ref : http://fhs.mcmaster.ca/main/news/news_2012/targeting_human_cancer_stem_cells.html

Onyx receives FDA approval for Kyprolis to treat multiple myeloma

 In continuation of my update on  Kyprolis.......

Onyx receives FDA approval for Kyprolis to treat multiple myeloma: The Multiple Myeloma Research Foundation (MMRF) today announced that its partner, Onyx Pharmaceuticals, Inc., received U.S. Food and Drug Administration (FDA) approval for Kyprolis (carfilzomib) for the treatment of patients with multiple myeloma who have received at least two prior therapies, including Velcade (bortezomib) for Injection and an immunomodulatory agent, such as Thalomid (thalidomide) or Revlimid (lenalidomide), and have demonstrated disease progression on or within 60 days of completion of the last therapy.....

FDA approves Cipher’s Absorica to treat severe recalcitrant nodular acne

FDA approves Cipher’s Absorica to treat severe recalcitrant nodular acne: Cipher Pharmaceuticals Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved Absorica, Cipher's novel, patented brand formulation of the acne medication isotretinoin (left structure), for the treatment of severe recalcitrant nodular acne.

APD421 Reduces Nausea, Vomiting....

Acacia Pharma announces positive results from its Phase 2 study of APD421, in the prevention of post-operative nausea and vomiting (PONV). The study showed that APD421 significantly reduced the incidence of nausea and vomiting compared to placebo in adult surgical patients at moderate-to-high risk of suffering PONV. Vomiting and especially nausea remain a major problem for patients after surgical operations, despite the availability of a number of approved anti-emetics.

APD421 comprises a completely new, patent-protected use of a currently marketed dopamine D2/D3 antagonist for the prevention and treatment of PONV.

The double-blind, Phase 2 study, comparing three doses of APD421 with placebo, was conducted in ten major centres in France, Germany and the USA, and recruited 223 surgical patients with two or more of the four established “Apfel” risk factors for PONV. The primary endpoint was protection against PONV, defined as no vomiting or retching and no requirement for anti-emetic rescue medication in the first 24 hours after surgery. APD421 was highly significantly superior to placebo at preventing PONV, the optimal dose approximately halving the PONV rate, from 67% in the placebo group to 36% (p=0.004). The incidence and severity of nausea were also significantly reduced.

APD421 was very well tolerated at all three dose levels, with no significant difference in the frequency of any adverse event for any dose of APD421 compared to placebo, and no serious adverse reactions. No prolongation of the QT interval was seen with APD421 nor was there any evidence of sedation, psychological symptoms, extrapyramidal toxicity or gastrointestinal disturbance, a clear advantage over many other anti-emetics.

Ref : http://www.acaciapharma.com/index.php/news/acacia_pharma_announces_excellent_phase_ii_results_for_apd421_in_ponv

FDA accepts NDA filing for KYNAMRO to treat HoFH...

In continuation of my update on Mipomersen...

Genzyme, a Sanofi company, and Isis Pharmaceuticals Inc., announced,  that the U.S. Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for KYNAMRO^™ (mipomersen sodium) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH).....

Diabetes Drug Could Be a Promising Therapy for Traumatic Brain Injury

In continuation of my update on Exendin-4

Research commissioned by the United States Air Force, Prof. Chaim Pick of Tel Aviv University's Sackler Faculty of Medicine and Dr. Nigel Greig of the National Institute of Aging in the US have discovered that Exendin-4, an FDA-approved diabetes drug, significantly minimizes damage in TBI animal models when administered shortly after the initial incident. Originally designed to control sugar levels in the body, the drug has recently been found effective in protecting neurons in disorders such as Alzheimer's disease.

Prof. Pick's collaborators include his TAU colleagues Dr. Vardit Rubovitch, Lital Rachmany-Raber, and Prof. Shaul Schreiber, and Dr. David Tweedie of the National Institute of Aging in the US. Detailed in the journal Experimental Neurology, this breakthrough is the first step towards developing a cocktail of medications to prevent as much brain damage as possible following injury....

American Friends of Tel Aviv University: Diabetes Drug Could Be a Promising Therapy for Traumatic Brain Injury

USPTO issues patent to MicuRx’s MRX-I antibacterial agent

USPTO issues patent to MicuRx’s MRX-I antibacterial agent: MicuRx Pharmaceuticals, Inc., a privately-held biopharmaceutical company developing next-generation antibiotics, today announced that the U.S. Patent and Trademark Office (USPTO) issued a composition of matter patent covering its clinical candidate, MRX-I. MRX-I is a novel antibacterial oxazolidinone (general structure of 2-oxazolidinone) that targets infections due to multi-drug resistant Gram-positive pathogens.

Azithromycin can be effective treatment option for patients with BOS

In continuation of my update on azithromycin

Azithromycin can be effective treatment option for patients with BOS: Researchers in the United Kingdom have determined that azithromycin, a broad-spectrum antibiotic that also has anti-inflammatory properties, can be an effective treatment option for patients suffering from bronchiolitis obliterans syndrome (BOS), a life-threatening complication that occurs in the majority of patients following lung transplantation.

Positive Results from Tesetaxel Study

Genta Incorporated announced results from its Phase 2 clinical trial using tesetaxel as initial, single-agent chemotherapy in women with  advanced breast cancer. Tesetaxel is an oral taxane in clinical development. The trial is lead by Memorial Sloan-Kettering Cancer Center, New York, NY, in collaboration with three other US centers.

Women were eligible if they had not received chemotherapy for locally advanced or metastatic HER2-negative breast cancer. Prior adjuvant chemotherapy was allowed if the recurrence was at least 12 months from the last dose. Forty-six patients were accrued to the trial, and 44 are currently evaluable for response. 70% of patients had received adjuvant chemotherapy; more than 80% of those regimens had included an injectable taxane. More than 50% of patients had received local radiotherapy, and approximately two-thirds had progressed on one more hormonal therapies.

Major objective responses were observed in 20 of 44 patients (45%), including one complete response and nineteen partial responses. Seven of the major responders cleared more than 75% of their measurable disease. The disease-control/clinical-benefit rate, which includes major responders and patients with stable disease, was 82%.

Exploratory analyses showed that 17 of 35 patients (49%) whose disease was estrogen receptor positive (ER+) had major responses. Median progression-free survival in the ER+ population was 7.3 months. In women with "triple-negative" disease, which is relatively insensitive to chemotherapy, 3 of 9 patients responded 33%.

Tivantinib Meets Study Endpoint

ArQule Inc. and Daiichi Sankyo Co. Ltd. announced that a Phase 2 trial data using tivantinib as a single agent investigational second-line treatment in hepatocellular carcinoma (HCC) met its primary endpoint. Now the full results from this trial will be presented at the 2012 Annual Meeting of American Society of Clinical Oncology, including positive data in the pre-defined c-MET high population. Additional clinical data with tivantinib will be featured in two poster discussions and two general poster sessions.

“These findings represent the first randomized data reported with an investigational c-MET inhibitor administered as a single agent second-line treatment in HCC,” said Paolo Pucci, chief executive officer of ArQule. “They clearly define c-MET high patients as a biological subgroup for potential targeted therapy with tivantinib. The robust statistical significance achieved in this trial reflects the anti-cancer activity of tivantinib alone and expands its therapeutic potential.”

Data from the HCC trial demonstrated a statistically significant improvement in time-to-progression (HR=0.43, log rank p-value=0.03), accompanied by significant improvements in progression-free survival and disease control rate among second-line patients with c-MET high tumors who were treated with tivantinib. In addition, overall survival data were observed favoring tivantinib-treated patients in this population. Efficacy was similar in the two tivantinib dosing subgroups (360 milligrams twice daily and 240 milligrams twice daily), with less frequent neutropenia in the lower dose.

Previously announced top-line data from the HCC trial demonstrate that treatment with tivantinib produced a statistically significant 56 percent improvement in TTP in the intent-to-treat (ITT) population by central radiology review, the primary endpoint (HR = 0.64, log rank p-value = 0.04) in this trial. Adverse events were reported at similar rates in the treatment and placebo arms, except for a higher incidence of fatigue and hematologic events, including neutropenia and anemia, in tivantinib-treated patients. The incidence of hematologic events declined following dose reduction of tivantinib from 360 milligrams twice daily to 240 milligrams twice daily.

Ref : http://investors.arqule.com/releasedetail.cfm?ReleaseID=674815

New anti-cancer drug developed

New anti-cancer drug developed

Successful Completion Of Proof-of-concept Clinical Trial Of Levotofisopam For The Treatment Of Gout

Pharmos Corporation,  announced that it has successfully completed a proof-of-concept clinical trial using its compound levotofisopam (5S)-1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine, S-tofisopam see structure below) to treat patients with hyperuricemia and gout. This phase 2a trial was conducted at the Duke Clinical Research Unit of Duke University and the principal investigator was John Sundy, MD, PhD, an expert and key opinion leader in the treatment of gout. The trial was designed to assess the safety and efficacy of levotofisopam as a uric acid-lowering agent in patients with gout.

The trial enrolled 13 patients in an open label study with patients confined in the Duke facility.  The study enrolled patients with screening serum urate between 8 and 12 mg/dL. Subjects received a single dose of 50 mg on days 1 and 7 and 50 mg TID on days 2 through 6.  Levotofisopam was well tolerated. The mean reduction in serum urate was over 45%. All 13 patients were responders, and demonstrated a serum urate level of less than 6 mg/dL on day 7. Seven subjects achieved a serum urate level less than 4 mg/dL on day 7. Additionally there was an increase in the fractional excretion of urate, confirming the compound's mechanism of action as a uricosuric agent that enhances urate excretion by the kidneys. 

Commenting on the results of this Phase 2a trial, the principal investigator Dr. John Sundy said, "monotherapy with levotofisopam was well tolerated and induced clinically important reductions in serum urate levels in all patients studied. These results support further development of levotofisopam for treating hyperuricemia in patients with gout."

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C: Achieves Up to 3.73 log10 Reduction in Genotype 1 HCV RNA After Three Days of Treatment With Once-Daily 400 mg ACH-2684 in Phase 1b Study : Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today reported...

Achillion Pharmaceuticals, Inc. reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684 (see below structure), a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.

 "We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV,"...

Heparin-like compounds inhibit breast cancer metastasis to bone

Heparin-like compounds inhibit breast cancer metastasis to bone: Researchers from VTT Technical Research Centre of Finland have in collaboration with the University of Turku, Indiana University and two Finnish companies, Biotie Therapies Corp. and Pharmatest Services Ltd, discovered a novel mechanism regulating...

Researchers,  subsequently showed how heparin and a high-molecular-weight Escherichia coli K5-derived heparin-like polysaccharide (K5-NSOS see below structure) inhibited TGF-β–induced IL-11 production in MDA-MB-231(SA) cells. In addition, K5-NSOS inhibited bone resorption activity of human osteoclasts in vitro. We evaluated the therapeutic potential of K5-NSOS and fragmin in a mouse model of breast cancer bone metastasis. MDA-MB-231(SA) cells were inoculated into the left cardiac ventricle of athymic nude mice which were treated with fragmin, K5-NSOS, or vehicle once a day for four weeks. Both heparin-like glycosaminoglycans inhibited weight reduction, decreased osteolytic lesion area, and reduced tumor burden in bone. In conclusion, our data imply novel mechanisms involved in TGF-β induction and support the critical role of heparan sulfate glycosaminoglycans in cancer metastasis as well as indicate that K5-NSOS is a potential antimetastatic and antiresorptive agent for cancer therapy. This study illustrates the potential to translate in vitro siRNA screening results toward in vivo therapeutic concepts.

 

Ref : http://mcr.aacrjournals.org/content/10/5/597.abstract

NSAIDs and Cardiovascular Risk Explained, According to Studies from the Perelman School of Medicine

NSAIDs and Cardiovascular Risk Explained, According to Studies from the Perelman School of Medicine: After nearly 13 years of study and intense debate, a pair of new papers from the Perelman School of Medicine, at the University of Pennsylvania have confirmed exactly how a once-popular class of anti-inflammatory drugs leads to cardiovascular risk for people taking...

Ref : http://www.uphs.upenn.edu/news/News_Releases/2012/05/risk/

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Research by a collaborative group of scientists from UC San Diego School of Medicine, UC San Francisco and Wake Forest School of Medicine has led to identification of an existing drug that is effective against Entamoeba histolytica. Using a high-throughput screen for drugs developed by the research team, they discovered that auranofin (see structure) a drug approved by the US Food and Drug Administration 25 years ago for rheumatoid arthritis -- is very effective in targeting an enzyme that protects amebae from oxygen attack (thus enhancing sensitivity of the amebae to reactive oxygen-mediated killing).

Entamoeba histolytica is a protozoan intestinal parasite that causes human amebiasis, the world's fourth leading cause of death from protozoan parasites. It is listed by the National Institutes of Health as a category B priority biodefense pathogen. Current treatment relies on metronidazole, which has adverse effects, and potential resistance to the drug is an increasing concern.

Study shows how a drug-lead compound suppresses tumour formation

Study shows how a drug-lead compound suppresses tumour formation: A team of scientists from the National University of Singapore's (NUS) Department of Biological Sciences and Mechanobiology Institute have discovered how a drug-led compound - a compound that is undergoing preclinical trials as a potential drug - can deprive cancer cells of energy and stop them from growing into a tumour. This drug-led compound is named BPTES (see below structure). This is the the first detailed descriptions of precisely how BPTES inhibits glutaminase....

 

Ref : http://www.pnas.org/content/109/20/7705.full

Scientists unravel action mechanism of castor oil

Scientists unravel action mechanism of castor oil: Castor oil is known primarily as an effective laxative; however, it was also used in ancient times with pregnant women to induce labour. Only now have scientists at the Max Planck Institute for Heart and Lung Research succeeded in unravelling the mysteries of the action mechanism. A receptor by the name of EP3 on the cells of the intestine and uterus is apparently responsible. This is activated by an ingredient, i.e., Ricinoleic acid (12-hydroxy-9-cis-octadecenoic acid) is an unsaturated omega-9 fatty acid in the oil, see the structure).

More : http://www.mpg.de/5808639/receptor_castor_oil

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA

In continuation of my update on Rivaroxaban

New Blood Thinner May Lower Chances of Clots in High-Risk Heart Patients: FDA:  The new blood thinner Xarelto appears to lower the chances of potentially fatal blood clots in high-risk heart patients, a U.S. Food and Drug Administration review has found.

Cobiprostone shows promise against NSAID-induced gastric mucosal injury

Cobiprostone shows promise against NSAID-induced gastric mucosal injury: Sucampo Pharmaceuticals, Inc. today announced the presentation of preclinical data at Digestive Disease Week 2012, in San Diego, which demonstrates the protective effect of cobiprostone (see structure)  against epithelial barrier dysfunction in models of non-steroidal anti-inflammatory drug (NSAID)-induced gastric mucosal injury.

Ref : http://investor.sucampo.com/phoenix.zhtml?c=201197&p=irol-newsArticle&ID=1697806&highlight=

Pernix Therapeutics introduces Omeclamox-Pak® for the treatment of H. pylori infection and duodenal ulcer disease

Pernix Therapeutics introduces Omeclamox-Pak® for the treatment of H. pylori infection and duodenal ulcer disease: Pernix Therapeutics Holdings, Inc., a specialty pharmaceutical company,  announced the introduction of Omeclamox-Pak®, a ten-day therapy of omeprazole (below 1st) delayed-release capsules (20 mg), clarithromycin (below 2nd) tablets (500 mg) and amoxicillin (below 3rd) capsules (500 mg) for the treatment of Helicobacter pylori (H. pylori) infection and duodenal ulcer disease (active or one-year history) to eradicate H. pylori in adult patients...

Two-Drug Combo (naproxen and sumatriptan) Helps Teens With Migraines

A two-drug combination that relieves migraines in adults also works well in adolescents, new research indicates.

Because the combination of Imitrex (sumatriptan see structure left) and naproxen (structure right) sodium (Aleve and other brand names) isn't approved for use by the U.S. Food and Drug Administration for this age group, doctors must prescribe it "off label" to adolescents.

"There are no FDA-approved abortive [migraine] treatments for children," said Dr. Noah Rosen, director of the Headache Center at the Cushing Neuroscience Institute in Great Neck, N.Y. "This is the first really large-scale abortive treatment study for adolescents."

Migraines in children and adolescents are physiologically no different from migraines in adults, said Drexler, although migraines in younger people tend not to last as long.

The class of drugs known as triptans are the most studied, but none of those trials have shown a great benefit, possibly because of a large placebo response, the study authors wrote.

Advanced Prostate Cancer Drug May Help at Earlier Stage

In continuation of my update on abiraterone

Advanced Prostate Cancer Drug May Help at Earlier Stage:  A drug approved to treat advanced prostate cancer appears to help men who have localized high-risk prostate cancer if given before surgery. Adding Zytiga (abiraterone) to conventional hormonal treatments eliminated or nearly...

Experimental Drug Helps Fight Some Childhood Cancers, Study Finds

In continuation of my update on Crizotinib

Experimental Drug Helps Fight Some Childhood Cancers, Study Finds:  A new targeted drug therapy may help treat certain advanced cancers in children, a new preliminary study indicates.In some cases, the oral medication even made tumors disappear after regular cancer treatments had failed, the...

Abiraterone acetate can help eliminate prostate tumors

In continuation of my update Abiraterone

Abiraterone acetate can help eliminate prostate tumors: A hormone-depleting drug approved last year for the treatment of metastatic prostate cancer can help eliminate or nearly eliminate tumors in many patients with aggressive cancers that have yet to spread beyond the prostate, according to a clinical study to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO), June 1-5, in Chicago.

Mylan receives final FDA approval for Clopidogrel Tablets ANDA

Mylan receives final FDA approval for Clopidogrel Tablets ANDA: Mylan Inc.  announced that its subsidiary Mylan Pharmaceuticals Inc. has received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for Clopidogrel Tablets USP, 75 mg and 300 mg.

Celery Chemical, Apigenin Tackles Breast Cancer

Apigenin, a natural substance found in grocery store produce aisles, shows promise as a non-toxic treatment for an aggressive form of human breast cancer, following a new study at the University of Missouri. MU researchers found apigenin shrank a type of breast cancer tumor that is stimulated by progestin, a synthetic hormone given to women in combination with estrogens to ease symptoms related to menopause.

“This is the first study to show that apigenin, which can be extracted from celery, parsley and many other natural sources, is effective against human breast cancer cells that had been influenced by a certain chemical used in hormone replacement therapy,” said co-author Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the College of Veterinary Medicine and the Dalton Cardiovascular Research Center.

In the study, Hyder and his colleagues implanted cells of a deadly, fast-growing human breast cancer, known as BT-474, into a specialized breed of mouse. Some of the mice were then treated with medroxyprogesterone acetate (MPA), a type of progestin commonly given to post-menopausal women. A control group did not receive MPA.

Later one group of MPA-treated mice was treated with apigenin. Cancerous tumors grew rapidly in the mice which did not receive apigenin. In the apigenin-treated mice, breast cancer cell growth dropped to that of the control group, and the tumors shrank.

New combination of two previously approved FDA drugs treat lung cancer

In continuation of my update on Erlotinib..

Dr. Narla's laboratory focuses on the identification and characterization of the genes and pathways involved in cancer metastasis. By studying the functional role of the KLF6 tumor suppressor gene, Dr. Narla and his team have identified new signaling pathways regulated by this gene family thus providing new insight into cancer diagnosis and treatment. The team's research found that KLF6 and FOXO1, both tumor suppressor genes, are turned off as cancer spreads through the body. By using a combination of two existing FDA drugs -Erlotinib (left structure), a targeted cancer drug, and Trifluoperazine (below right structure), a medication used to treat schizophrenia, the team developed an understanding of the properties that turn these critical genes back on, initiating tumor cells to die.

Since first discovering the KLF6 gene 13 years ago as a medical student at the Mount Sinai School of Medicine in the laboratory of Dr. Scott Friedman, Dr. Narla has been involved in the identification and characterization of the KLF6 gene and its role in cancer development and the progression of cancer.

Read details at JCI.....

New combination of two previously approved FDA drugs treat lung cancer

Caffeine can prevent memory loss in diabetes

Caffeine can prevent memory loss in diabetes: Badly controlled diabetes are known to affect the brain causing memory and learning problems and even increased incidence of dementia, although how this occurs is not clear. But now a study in mice with type 2 diabetes has discovered how diabetes affects a brain area called hippocampus causing memory loss, and also how caffeine can prevent this. 

Isis commences ISIS-APOCIIIRx Phase 2 study in hypertriglyceridemia

Isis commences ISIS-APOCIIIRx Phase 2 study in hypertriglyceridemia: 

Isis Pharmaceuticals, Inc. announced the initiation of a Phase 2 study 

evaluating ISIS-APOCIIIRx in patients with hypertriglyceridemia......

Ref:http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle_pf&ID=1509616

Potential new drugs for fox tapeworm infection in humans

Potential new drugs for fox tapeworm infection in humans: Scientists are reporting development and testing of a new series of drugs that could finally stop the fox tapeworm  which causes a rare but life-threatening disease in humans  dead in its tracks. The report shows that specific organometallic substances that help combat cancer are also the surprising best new hope for a treatment against tapeworm infection.

The group prepared and evaluated several ruthenium complexes (see structure)

as potential drugs against the fox tapeworm. Some were effective in killing the tapeworms and also were less toxic on normal cells in laboratory dish tests, making them prime candidates for further development as treatments for AE.

Ref : http://pubs.acs.org/doi/full/10.1021/jm300291a#showFigures
        http://pubs.acs.org/doi/suppl/10.1021/jm300291a/suppl_file/jm300291a_si_001.pdf

Phase I clinical trial shows drug shrinks melanoma brain metastases

The drug dabrafenib (see structure), which targets the Val600 BRAF mutation that is active in half of melanoma cases, also cut the size of tumors in 25 of 36 patients with late-stage melanoma that had not spread to the brain. The drug also showed activity in other cancer types with the BRAF mutation.

"Nine out of 10 responses among patients with brain metastases is really exciting. No other systemic therapy has ever demonstrated this much activity against melanoma brain metastases," said study co-lead author Gerald Falchook, M.D., assistant professor in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center.

Phase I clinical trial shows drug shrinks melanoma brain metastases

Scientists Discover Drug Candidate for Alzheimer’s, Huntington’s

Scientists at the Gladstone Institutes have identified a drug candidate that diminishes the effects of both Alzheimer's disease and Huntington's disease in animal models, offering new hope for patients who currently lack any medications to halt the progression of these two debilitating illnesses.

Gladstone Investigator Paul Muchowski, PhD, has identified a new compound called JM6 in experiments done in collaboration with an international team of researchers, and which are being published today in an online article in Cell. In laboratory tests involving mice genetically engineered to model one or the other of the two diseases, Dr. Muchowski's team found that JM6 blocks kynurenine 3-monooxygenase (KMO), an enzyme that has long been speculated to play a role in neurodegenerative diseases.

In mice modeling Alzheimer's disease, the novel compound prevented memory deficits and the loss of synaptic connections between brain cells—both of which are key features of the human disease. In mice modeling Huntington's disease, JM6 prevented brain inflammation and the loss of synaptic connections between brain cells, while also extending lifespan.

“This discovery has significant implications for two devastating diseases and suggests that the KMO enzyme is a good protein for us to target with medications in diverse neurodegenerative disorders,” said Lennart Mucke, MD, who oversees all neurological research at Gladstone and who won the prestigious Potamkin Prize last year for developing experimental strategies to make the brain more resistant to Alzheimer's. “With any luck, Dr. Muchowski and his colleagues could begin testing this drug in patients within the next two years.”

Remarkably, JM6 (see structure) does not penetrate into the brain, but works by inhibiting KMO in the blood. The blood cells then send a protective signal to the brain, to stabilize brain-cell function and prevent neurodegeneration. The fact that the compound does not pass the so-called blood-brain barrier will facilitate testing in patients, as JM6's potential impact could be confirmed with a simple blood test.

JM6 was named for Dr. Muchowski's father, Dr. Joseph Muchowski, PhD, a retired medicinal chemist who helped his son devise the novel KMO inhibitor. The study was carried out in collaboration with the laboratories of Dr. Robert Schwarcz, a University of Maryland School of Medicine professor who pioneered studies linking KMO and metabolically related enzymes to nerve-cell loss, and Professor Eliezer Masliah at the University of California, San Diego, an expert in neuropathology.

 Ref : www.cell.com/abstract/S0092-8674(11)00581-2

Positive Results of Diltiazem from Fissure Trial

Ventrus Biosciences Inc. reported positive results from its Phase 3, randomized, double-blind, placebo-controlled clinical trial of diltiazem hydrochloride cream (VEN 307) in patients with anal fissures.

Ventrus' development partner, S.L.A. Pharma, has completed most of the outputs for the statistical analysis plan of the Phase 3 trial, and Ventrus is pleased to communicate the data that they have generated.

The Phase 3 study randomized 465 subjects to diltiazem hydrochloride 4% or 2% w/w cream, or placebo, applied topically three times daily (TID) for 8 weeks, followed by a 4 week blinded observation period. Both 4% and 2% diltiazem treatment arms demonstrated significant improvements compared to placebo in the primary endpoint of average of worst anal pain associated with or following defecation (pain score improvement 0.44, p=0.0108, 4%; 0.43, p=0.0134, 2%) and in the secondary endpoints of overall anal-fissure-related pain (pain score 0.36, p=0.030, 4%; 0.40, p=0.0183, 2%) and anal fissure healing (32.7%, p=0.0181, 4%; 31.2%, p=0.0359, 2%). Pain endpoints were assessed using an 11-point numerical pain rating scale (Likert-like scale).

Adverse events (AEs) were similar for the three treatment arms. Gastrointestinal Disorders were the most common. Reports of headaches were similar in the three arms (14.7% of 4% diltiazem, 12.3% of 2% diltiazem, and 14.2% of placebo). There was one serious adverse event of surgery for hemorrhoid reported in this trial. The study was conducted in 31 centers in Europe by S.L.A. Pharma, the product candidate's licensor. Ventrus holds rights to diltiazem hydrochloride cream in North America.

Based on these results, Ventrus will request a meeting with the U.S. Food and Drug Administration (FDA) to discuss the Phase 3 diltiazem study, as well as steps to move forward toward a New Drug Application (NDA). Because diltiazem is approved in oral formulations for the treatment of angina and high blood pressure, it is eligible for the FDA's 505(b)2 registration pathway. The Company is also preparing to initiate a second pivotal Phase 3 study of VEN 307 in anal fissures in the second half of 2012.

Ref : http://investor.ventrusbio.com/releasedetail.cfm?ReleaseID=672924