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