Liver Cancer Drug Fails to Live Up to Early Promise...

In continuation of my update on everolimus

Although it looked promising in early studies, the drug everolimus didn't improve survival for people with advanced liver cancer in its latest trial, a new study found.

The findings from the phase 3 clinical trial are disappointing because earlier research suggested that everolimus (Afinitor) prevented tumor progression and improved survival for in advanced liver cancer. Normally, these patients can expect a median overall survival of less than one year.

The only drug currently shown to significantly improve survival of advanced liver cancer patients is sorafenib (Nexavar). But that drug's benefits are temporary and the cancer eventually progresses, according to background information in the new study.

The current study included 546 adults with advanced liver cancer whose disease progressed during or after treatment with sorafenib, or who could not take sorafenib. The patients were divided into two groups, with 362 given everolimus and 184 given a placebo.

Liver Cancer Drug Fails to Live Up to Early Promise 

New Inhaled Drug Shows Promise Against Asthma, Allergies...........

A new inhaled medication has the potential to treat mild asthma and allergies by interrupting the production of an immune system protein that triggers allergic reactions, a new study reports.

The drug, quilizumab, targets the blood cells that produce a protein called immunoglobulin type E (IgE), that serves a key role in allergies.

Quilizumab lowered total levels of IgE in the blood of people with allergies and mild asthma, and kept them low for a month, researchers report in the July 2 issue of the journal Science Translational Medicine.

"The subjects who received the drug not only had a reduction in their total IgE level, it also seemed to block production of new IgE in response to the allergen they inhaled," said study co-author Dr. Jeffrey Harris, principal medical director of immunology, tissue growth and repair for the drug manufacturer Genentech, which produces quilizumab and funded the study.

However, one expert noted that the drug has yet to prove itself against moderate to severe asthma.

New Inhaled Drug Shows Promise Against Asthma, Allergies  

New Inhaled Drug Shows Promise Against Asthma, Allergies - Drugs.com MedNews

A new inhaled medication has the potential to treat mild asthma and allergies by interrupting the production of an immune system protein that triggers allergic reactions, a new study reports.

The drug, quilizumab, targets the blood cells that produce a protein called immunoglobulin type E (IgE), that serves a key role in allergies.

Quilizumab lowered total levels of IgE in the blood of people with allergies and mild asthma, and kept them low for a month, researchers report in the July 2 issue of the journal Science Translational Medicine.

"The subjects who received the drug not only had a reduction in their total IgE level, it also seemed to block production of new IgE in response to the allergen they inhaled," said study co-author Dr. Jeffrey Harris, principal medical director of immunology, tissue growth and repair for the drug manufacturer Genentech, which produces quilizumab and funded the study.

However, one expert noted that the drug has yet to prove itself against moderate to severe asthma.

New Inhaled Drug Shows Promise Against Asthma, Allergies  

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study

Women with polycystic ovary syndrome have a better chance of getting pregnant if they take a breast cancer drug instead of the currently preferred medication, a new study suggests.

Polycystic ovary syndrome -- the most common cause of female infertility in the United States -- causes higher than normal levels of the male hormone androgen, infrequent periods and small cysts on the ovaries. It affects 5 to 10 percent of reproductive-age women, according to background information in the study.

Currently, doctors typically prescribe clomiphine (Clomid) to boost fertility for women with polycystic ovary syndrome. However, this new study suggests the drug letrozole (Femara) results in better ovulation, conception and birth rates.

"We found a simple and comparatively safe and vastly more effective treatment for [polycystic ovary syndrome]," said lead researcher Dr. Richard Legro, a professor of obstetrics and gynecology at Penn State University's College of Medicine in Hershey, Penn.

Clomiphine, which works by stimulating ovulation, has been the standard treatment for years, but has a high rate of multiple births, Legro said.

Letrozole, a treatment for breast cancer in postmenopausal women, works by blocking estrogen production, tricking the ovaries into producing more of the hormone, he explained.

The new study, funded by the U.S. National Institutes of Health, was published July 10 in the New England Journal of Medicine.

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study - Drugs.com MedNews

First drug candidate from NIH program acquired by biopharmaceutical company

A drug candidate developed by researchers at the NIH’s National Center for Advancing Translational Sciences (NCATS) and its collaborators to treat sickle cell disease has been acquired by Baxter International’s BioScience business. The drug candidate, Aes-103, is the first specifically developed to target the underlying molecular mechanism of sickle cell disease. Baxter now will advance the clinical development activities required for regulatory approval and commercialization.

Sickle cell disease is a genetic blood disorder that affects millions worldwide, including approximately 100,000 people in the United States — among them, 1 in 500 African-Americans.

This is the first time a company has acquired a drug candidate developed with NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program resources. Baxter International recently acquired AesRx, LLC, Newton, Massachusetts — the TRND program collaborator — including Aes-103. TRND and AesRx researchers worked together to develop Aes-103 through a Phase II clinical trial to evaluate safety and effectiveness. The trial data indicated that Aes-103 significantly reduced patients’ pain. 

“This is a wonderful example of why NCATS was created,” said NIH Director Francis S. Collins, M.D., Ph.D. “The progress made thus far in the development of Aes-103 demonstrates NCATS’ catalytic role in bringing together the necessary players, whether academic, nonprofit or industry, to overcome obstacles to translation and advance badly needed treatments to patients.”

First drug candidate from NIH program acquired by biopharmaceutical company

New Amyloid Reducing Compound Could Be a Preventive Measure Against Alzheimer’s | Neuroscience News Research Articles | Neuroscience Social Network

New Amyloid Reducing Compound Could Be a Preventive Measure Against Alzheimer’s | Neuroscience News Research Articles | Neuroscience Social Network



Ref : http://onlinelibrary.wiley.com/doi/10.1002/ana.24149/abstract;jsessionid=9F003DBC49DC78B99E15FC97CC073CFA.f01t03

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study - Drugs.com MedNews

A pill that blocks male hormone activity can improve survival and delay the need for chemotherapy in men with advanced prostate cancer, a new clinical trial has found.

Men who took a daily dose of the drug enzalutamide started chemotherapy nearly a year and a half later than men who received a placebo, even though their prostate cancer had spread to other parts of their bodies, said senior study author Dr. Tomasz Beer, deputy director of the Knight Cancer Center at Oregon Health and Science University.

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study

New Drug May Treat Constipation Caused by Strong Painkillers - Drugs.com MedNews

A new drug holds promise as a safe and effective treatment for constipation caused by prescription narcotic painkillers, new research states.

Constipation is a common side effect experienced by patients taking these powerful medications for chronic pain. When laxatives failed to provide relief, two phase 3 trials found the once-daily drug naloxegol could help.

"The studies showed rapid and sustained improvement for these patients, without compromising their pain management," study author Dr. William Chey, a gastroenterologist and professor of internal medicine at the University of Michigan Health System, said in a university news release.

The U.S. Food and Drug Administration, as well as health agencies in Canada and Europe, are reviewing the drug for possible approval.

Naloxegol (structure) was specifically designed to treat constipation caused by the narcotic painkillers that are often used to treat chronic health issues, such as osteoarthritis and back pain. These medications ease patients' pain by binding to certain receptors in the brain, but they also bind to receptors in the bowel, which raises the risk of constipation.

Naloxegol works by preventing the painkillers from binding to receptors in the bowel, but not the brain, according to the news release.

One of the new studies involved 652 people. The other study included 700 participants. The patients were randomly assigned to receive one 12.5 milligram (mg) or one 25 mg dose of naloxegol daily, or an inactive placebo.

New Drug May Treat Constipation Caused by Strong Painkillers 

Green tea could reduce pancreatic cancer risk: Study explains how

A study recently published online by the journal, Metabolomics, offers an explanation that researchers say could open a new area of cancer-fighting research. The study reports that EGCG, the active biologic constituent in green tea, changed the metabolism of pancreatic cancer cells by suppressing the expression of an enzyme associated with cancer, LDHA.

The researchers also found an enzyme inhibitor, oxamate, which is known to reduce LDHA activity, operated in the same manner: It also disrupted the pancreatic cancer cells metabolic system.

"Scientists had believed they needed a molecular mechanism to treat cancer, but this study shows that they can change the metabolic system and have an impact on cancer," said Wai-Nang Lee, MD, corresponding author of the study and a Los Angeles Biomedical Research Institute (LA BioMed) lead researcher. "By explaining how green tea's active component could prevent cancer, this study will open the door to a whole new area of cancer research and help us understand how other foods can prevent cancer or slow the growth of cancerous
cells."

Using sophisticated metabolic profiling methods, the researchers found EGCG disrupted the balance of "flux" throughout the cellular metabolic network. Flux is the rate of turnover of molecules through a metabolic pathway. The researchers found the EGCG disrupted this balance in the same manner that oxamate, a known LDHA inhibitor, did.

Based on this finding, they concluded that both EGCG and oxamate reduced the risk of cancer by suppressing the activity of LDHA, a critical enzyme in cancer metabolism, thereby disrupting the balance in the cancer cells metabolic functions.

Green teacould reduce pancreatic cancer risk: Study explains how  

New drug for non-Hodgkin lymphoma, chronic lymphocytic leukemia passes early test

The drug,
alisertib or MLN8237, inhibits the enzyme aurora A kinase, which is known to be
very active during cell division. The present study, published in the journalInvestigational
New Drugs, looks at the safety, tolerability, and preliminary success of
alisertib in treating non-Hodgkin lymphoma (NHL) and chronic lymphocytic
leukemia (CLL).

"An advantage with this drug is it is oral and very effective in a significant number of patients with aggressive lymphoma when used at that dose for 7  days out a 21 day cycle," said hematologist Swaminathan Iyer, M.D., who led the multi-site study. 

Drugs commonly used to treat NHL and CLL are chemotherapeutic drugs and some biological targeted agents such as the monoclonal antibodies rituximab, ofatumumab and obinutuzumab with varying degrees of success.

Although about 1/2 of patients participating in the phase I study experienced side effects most of which were manageable events, Iyer said that is not unusual for such
biologic (non chemotherapy) drugs.

"The side effects were fairly tolerable in this study," Iyer said. "We would like to see more information from a larger group of patients to fully understand the drug's safety and tolerability for those experiencing the middle-to-later stages of these diseases."

Iyer and his group recommend 50 mg, twice-daily doses of alisertib for the advanced phase trials of the drug, which Iyer says has begun enrollment. Alisertib is not yet approved for general medical use by the FDA. Its impact on T cell lymphoma is being investigated in a separate, phase III trial for a specific type of  lymphoma called the T cell lymphomas. Houston Methodist is a participating study site for that project. Initial phase II reports in these T cell lymphomas showed a 57% response, the highest ever noted for any single agent in this disease entity.

New drug
for non-Hodgkin lymphoma, chronic lymphocytic leukemia passes early test  

Leptin also influences brain cells that control appetite, researchers find -- ScienceDaily

Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of cells to control appetite...

Published in the June 1 issue of Nature Neuroscience, the findings could lead to development of treatments for metabolic disorders such as obesity and diabetes. "Up until now, the scientific community thought that leptin acts exclusively in neurons to modulate behavior and body weight," said senior author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine. "This work is now changing that paradigm."

Leptin, a naturally occurring hormone, is known for its hunger-blocking effect on the hypothalamus, a region in the brain. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.

Leptin's effect on metabolism has been found to control the brain's neuronal circuits, but no previous studies have definitively found that leptin could control the behavior of cells other than neurons.

To test the theory, Horvath and his team selectively knocked out leptin receptors in the
adult non-neuronal glial cells of mice. The team then recorded the water and food intake, as well as physical activity every five days. They found that animals responded less to feeding reducing effects of leptin but had heightened feeding responses to the hunger hormone ghrelin.

"Glial cells provide the main barrier between the periphery and the brain," said Horvath. "Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes."

Leptin also influences brain cells that control appetite, researchers find 

New therapy for pancreatic cancer patients shows promising results -- ScienceDaily

New therapy for pancreatic cancer patients shows promising results 

A Cinical trial conducted by researchers at the Virginia G. Piper Cancer Center Clinical Trials, a partnership between Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), showed that a new drug called MM-398 (below structure), given in combination with 5-flourouracil (5FU) and leucovorin, produced a significant overall survival rate in patients with advanced, previously-treated pancreatic cancer.

FDA Approves Incruse Ellipta...

GlaxoSmithKline plc today announced that the US Food and Drug Administration (FDA) has approved Incruse Ellipta (umeclidinium) as an anticholinergic indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Umeclidinium is GSK’s first once-daily anticholinergic, a type of bronchodilator also known as a long-acting muscarinic antagonist (LAMA), and is contained in the Ellipta® inhaler. The FDA-approved strength is 62.5 mcg.

Following this approval by the FDA, it is anticipated that launch activities in the US will commence during the fourth quarter of 2014.

The phase III pivotal programme for umeclidinium included seven clinical studies which involved over 2,500 COPD patients treated with umeclidinium or placebo.

Incruse Ellipta (umeclidinium) Information from Drugs.com

FDA Approves Zontivity to Reduce the Risk of Heart Attacks and Stroke

The U.S. Food and Drug Administration  approved Zontivity (vorapaxar) tablets to reduce the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore the blood flow to the heart in patients with a previous heart attack or blockages in the arteries to the legs.

Zontivity is the first in a new class of drug, called a protease-activated receptor-1 (PAR-1) antagonist. It is an anti-platelet agent, designed to decrease the tendency of platelets to clump together to form a blood clot. By decreasing the formation of blood clots, Zontivity decreases the risk of heart attack and stroke.

Like other drugs that inhibit blood clotting, Zontivity increases the risk of bleeding, including life-threatening and fatal bleeding. Bleeding is the most commonly reported adverse reaction in people taking Zontivity. The drug’s prescribing information (label) includes a Boxed Warning to alert health care professionals about this risk.

Zontivity must not be used in people who have had a stroke, transient ischemic attack (TIA), or bleeding in the head, because the risk of bleeding in the head is too great.

“In patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death. In the study that supported the drug’s approval, Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research.

FDA Approves Zontivity to Reduce the Risk of Heart Attacks and Stroke

Amrubicin promise for etoposide-naïve SCLC patients

Patients with chemotherapy-refractory small-cell lung cancer (SCLC) may benefit from treatment with the topoisomerase II inhibitor amrubicin, research from Japan suggests.

The 82 patients enrolled in the open-label, single-arm Japan Clinical Oncology Group Study JCOG0901 trial received amrubicin 40 mg/m2 for 3 days on a 21-day cycle, for a median of four cycles. All patients had already experienced no response, or progression, following treatment with at least one platinum-based regimen, with 51.2% previously treated with etoposide and 57.3% with irinotecan.

The overall response rate, defined as an independently assessed complete or partial response, was highly significant, at 32.9%, compared with a null hypothesis threshold of 10.0% or below. Median progression-free survival was 3.5 months and overall survival was 8.9 months, with over a third (35.7%) of patients alive 1 year later.

And amrubicin showed particular promise for patients who had not previously received etoposide, another type of topoisomere II inhibitor, say Haruyasu Murakami (Shizuoka Cancer Center) and colleagues.

Etoposide-naïve patients achieved an objective response rate of 45.0%, compared with 21.4% for those previously treated with the agent, a significant difference.

Both median progression-free survival and overall survival were also significantly higher in etoposide-naïve than pretreated patients, at 5.1 versus 2.9 months and 13.1 versus 7.9 months, respectively.

The reduced benefit of amrubicin found in patients previously treated with etoposide may be due to downregulation of topoisomerase II following the initial treatment, Murakami et al suggest in Lung Cancer.

Amrubicin promise for etoposide-naïve SCLC patients