Friday, November 20, 2015

FDA approves Endo’s BELBUCA (buprenorphine) buccal film for use in patients with chronic pain

New treatment option combines proven efficacy and established safety profile of buprenorphine with a novel delivery system that adds convenience and flexibility.

http://upload.wikimedia.org/wikipedia/commons/0/04/

Endo Pharmaceuticals Inc., a subsidiary of Endo International plc (NASDAQ: ENDP) (TSX: ENL), and BioDelivery Sciences International, Inc. (NASDAQ: BDSI), announced today that the U.S. Food and Drug Administration (FDA) has approved BELBUCA™ (buprenorphine) buccal film for use in patients with chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.  BELBUCA™, which is the first and only buprenorphine developed with a dissolving film that is absorbed through the inner lining of the cheek for chronic pain management, is expected to be commercially available in the U.S. during the first quarter of 2016 in seven dosage strengths, allowing for flexible dosing ranging from 75 μg to 900 μg every 12 hours. This enables physicians to individualize titration and treatment based on the optimally effective and tolerable dose for each patient.

“The availability of new, convenient and flexible treatment options is important for patients whose lives are burdened by chronic pain, a debilitating condition that affects more Americans than diabetes, heart disease and cancer combined,” said Richard L. Rauck, M.D., Director of Carolinas Pain Institute, Winston Salem, NC. “BELBUCA™ provides a unique approach for chronic pain management, combining the proven efficacy and established safety of buprenorphine with a novel buccal film delivery system that adds convenience and flexibility. For both opioid-naïve and opioid-experienced patients who require around-the-clock treatment and for whom alternative treatment options are inadequate, BELBUCA™ offers appropriate, consistent pain relief and a low incidence of typical opioid-like side effects.”

BELBUCA™ is a mu-opioid receptor partial agonist and a potent analgesic with a long duration of action that utilizes BDSI’s patented BioErodible MucoAdhesive (BEMA®) drug delivery technology. Through this unique delivery system, buprenorphine is efficiently and conveniently delivered across the buccal mucosa (inside lining of the cheek). Buprenorphine is a Schedule III controlled substance, meaning that it has been defined as having lower abuse potential than Schedule II drugs, a category that includes most opioid analgesics. Among chronic pain patients taking opioids, the vast majority are on daily doses of 160 mg of oral morphine sulfate equivalent (MSE) or less. With seven dosage strengths up to 160 mg MSE, BELBUCA™ offers a treatment choice for a wide range of opioid needs in chronic pain sufferers.


Last resort antibiotics may no longer work

Last resort antibiotics may no longer work

Antiviral agent protects rhesus monkeys from deadly Ebola virus

Rhesus monkeys were completely protected from the deadly Ebola virus when treated three days after infection with a compound that blocks the virus's ability to replicate. These encouraging preclinical results suggest the compound, known as GS-5734, should be further developed as a potential treatment, according to research findings to be presented tomorrow at the IDWeek conference.

Travis Warren, Ph.D., a principal investigator at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), said the work is a result of the continuing collaboration between USAMRIID and Gilead Sciences of Foster City, Calif. Scientists at the Centers for Disease Control and Prevention (CDC) also contributed by performing initial screening of the Gilead Sciences compound library to find molecules with promising antiviral activity.

The initial work identified the precursor to GS-5734, a small-molecule antiviral agent, which led to the effort by Gilead and USAMRIID to further refine, develop and evaluate the compound. Led by USAMRIID Science Director Sina Bavari, Ph.D., the research team used cell culture and animal models to assess the compound's efficacy against several pathogens, including Ebola virus.

In animal studies, treatment initiated on day 3 post-infection with Ebola virus resulted in 100 percent survival of the monkeys. They also exhibited a substantial reduction in viral load and a marked decrease in the physical signs of disease, including internal bleeding and tissue damage.

"The compound, which is a novel nucleotide analog prodrug, works by blocking the viral RNA replication process," said Warren. "If the virus can't make copies of itself, the body's immune system has time to take over and fight off the infection."

In cell culture studies, GS-5734 was active against a broad spectrum of viral pathogens. These included Lassa virus, Middle East Respiratory Syndrome (MERS) virus, Marburg virus, and multiple variants of Ebola virus, including the Makona strain causing the most recent outbreak in West Africa.

Ref : https://idsa.confex.com/idsa/2015/webprogram/Paper54208.html

Thursday, November 19, 2015

YK-4-279 compound works against some forms of leukemia: Study

A compound discovered and developed by a team of Georgetown Lombardi Comprehensive Cancer Center researchers that halts cancer in animals with Ewing sarcoma and prostate cancer appears to work against some forms of leukemia, too. That finding and the team's latest work was published online Oct. 8 in Oncotarget. 

YK-4-279 Chemical Structure

The compound is YK-4-279, the first drug targeted at similar chromosomal translocations found in Ewing sarcoma, prostate cancer and in some forms of leukemia. Translocations occur when two normal genes break off from a chromosome and fuse together in a new location. This fusion produces new genes that manufacture proteins, which then push cancer cells to become more aggressive and spread. One of those proteins is EWS-FLI1. YK-4-279 appears effective in controlling the cancer promoting functions of EWS-FLI1.

"EWS-FLI1 is already known to drive a rare but deadly bone cancer called Ewing sarcoma, which occurs predominantly in children, teens and young adults," says Aykut Üren, MD, professor of molecular oncology at Georgetown Lombardi. "It also appears to drive cancer cell growth in some prostate cancers."
In this new study led by Üren, mice with EWS-FLI1-driven leukemia were given injections of YK-4-279 five days per week for two weeks and compared with untreated mice. By the end of the first week the mice receiving YK-4-279 had much lower numbers of leukemia cells. At the end of two weeks the treated mice were nearly normal by many measures, while the untreated mice had overwhelming numbers of cancer cells and died on average after three weeks, the researchers say. By contrast, mice receiving only two weeks of YK-4-279 lived nearly three times as long.

"The fact that treated mice did not get sick from the YK-4-279 gives us an early indication that it might be safe to use in humans, but that is a question that can't be answered until we conduct clinical trials," Üren explains. "We are looking for ways that would allow us to administer more of it, or even to formulate a pill."

Üren says much more work remains for the team in order to translate this drug from a laboratory application into clinical trials.

Support for this work came from the Children's Cancer Foundation, St. Baldrick's Foundation, Go4theGoal, the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the Austrian Science Fund (FWF), the Children´s Cancer Research Institute and from grants from the National Institutes of Health (RC4CA156509, R01CA133662, R01CA138212).

Wednesday, November 18, 2015

First patients screened in Axovant's phase 3 study of RVT-101



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Axovant Sciences Ltd. (NYSE: AXON), a leading clinical-stage biopharmaceutical company focused on the treatment of dementia, recently announced the first patients screened in MINDSET, a confirmatory global phase 3 study of Axovant's lead product candidate, RVT-101. Axovant also announced that the company and the U.S. Food and Drug Administration (FDA) have agreed to a Special Protocol Assessment (SPA) supporting this phase 3 program.

MINDSET is an international, multi-center, double blind, placebo-controlled study designed to evaluate the safety, tolerability and efficacy of RVT-101 in patients with mild-to-moderate Alzheimer's disease. The 24-week trial will compare 35-mg, once-daily oral doses of RVT-101 to placebo in approximately 1,150 patients with mild-to-moderate Alzheimer's disease on a stable background of donepezil therapy. The primary efficacy evaluations are the Alzheimer's Disease Assessment Scale – cognitive subscale (ADAS-cog) and the Alzheimer's Disease Cooperative Study – Activities of Daily Living scale (ADCS-ADL), each of which have been used as endpoints to obtain regulatory approval of currently-marketed Alzheimer's disease treatments in the United States and Europe.
The MINDSET trial is designed to confirm the results of a 684-patient international, multi-center, double-blind placebo-controlled study in which patients on a stable background of donepezil therapy receiving 35 mg RVT-101 demonstrated statistically significant improvements on the ADAS-cog and ADCS-ADL as compared to patients receiving donepezil alone.

"I am grateful for the unwavering efforts of the entire development team that has so rapidly advanced RVT-101 into this final stage of the drug development process," said Axovant Chief Development Officer Dr. Lawrence Friedhoff, who is leading the RVT-101 development program and previously led the development program for donepezil (brand name Aricept®), the most widely used Alzheimer's treatment.

"No new compounds have been approved for Alzheimer's disease in over a decade, and physicians are scrambling to do more for their patients," said Dr. Gary Small, President of the American Association for Geriatric Psychiatry. "We need well-tolerated, once-daily oral treatments that provide clinically meaningful benefits. The start of the MINDSET study is an important milestone for the field of Alzheimer's drug development."

Tuesday, November 17, 2015

Tarix Orphan's TXA127 granted FDA Fast Track Designation for treatment of DMD patients

Tarix Orphan LLC, a privately held biopharmaceutical company focused on the treatment of rare neuromuscular disorders and connective tissue diseases, today announced that the U.S. Food and Drug Administration has granted Fast Track Designation to TXA127 (angiotensin 1-7) to reduce skeletal muscle damage and fibrosis and thereby improve muscle strength in Duchenne Muscular Dystrophy (DMD) patients. Tarix Orphan has received notice that clinical testing under the company's Investigational New Drug (IND) application for TXA127 may proceed, and the company expects to initiate a multi-site Phase 2 safety and efficacy study in patients with DMD in early 2016 at both U.S. and European trial sites. Tarix has previously received Orphan Drug Status for TXA127 in the DMD indication in both the United States and Europe.


"Studies with TXA127 have shown significant development potential in preclinical models of Duchenne Muscular Dystrophy, Limb Girdle Muscular Dystrophy, and congenital muscular dystrophy, MDC1A and other conditions associated with the TGF-beta pathway. This peptide has several biological actions and has shown positive effects in animals including reductions in muscle fibrosis, increases in muscle strength and ambulation in affected animals, as well as normalization of cardiac dysfunction," said Rick Franklin, Tarix Orphan Chief Executive Officer. "We look forward to beginning our multi-site international Phase 2 study in DMD patients in early 2016. We are additionally preparing a clinical protocol for a study of TXA127 in children with congenital muscular dystrophy (MDC1A), and hope to initiate studies in 2016 in that indication, for which there are no current treatments."

The planned Phase 2 trial will be a double-blind, randomized, placebo-controlled safety and efficacy study of TXA127 in 45 ambulant patients with DMD, conducted for 48 weeks, followed by a 96-week open-label extension study. The study will be conducted at 3 sites in the United States and 3 in Europe. Endpoints for the study will include assessment of muscle quality by MRI, ambulatory assessments including the 2-Minute Walk Test, and safety assessments.

Monday, November 16, 2015

Solix Algredients introduces Solasta Astaxanthin to B2B marketplace

We know that, Astaxanthin /æstəˈzænθɨn/ is a keto-carotenoid.  It belongs to a larger class of chemical compounds known as terpenes, which are built from five carbon precursors; isopentenyl diphosphate (or IPP) and dimethylallyl diphosphate (or DMAPP). Astaxanthin is classified as a xanthophyll (originally derived from a word meaning "yellow leaves" since yellow plant leaf pigments were the first recognized of the xanthophyll family of carotenoids), but currently employed to describe carotenoid compounds that have oxygen-containing moities, hydroxyl (-OH) or ketone (C=O), such as zeaxanthin and canthaxanthin. Indeed, astaxanthin is a metabolite of zeaxanthin and/or canthaxanthin, containing both hydroxyl and ketone functional groups. Like many carotenoids, astaxanthin is a colorful, lipid-soluble pigment. This colour is due to the extended chain of conjugated (alternating double and single) double bonds at the centre of the compound. This chain of conjugated double bonds is also responsible for the antioxidant function of astaxanthin (as well as other carotenoids) as it results in a region of decentralized electrons that can be donated to reduce a reactive oxidizing molecule.

Solix Algredients, Inc. has introduced Solasta™ Astaxanthin to the B2B ingredients marketplace.

Skeletal formula of astaxanthin

Solasta™ is a natural astaxanthin extract produced from the microalga Haematococcus pluvialis, the richest natural source of the antioxidant. Research has shown that algal astaxanthin has superior antioxidant activity compared to other well-known antioxidants.

Solasta™ Astaxanthin is an excellent source of astaxanthin for use in dietary supplement and personal care applications. Solasta™ is non-GMO, vegetarian, and extracted in the USA. The extraction uses super-critical carbon dioxide to ensure the safety, quality, and consistency of Solasta™.

Solix Algredients is now leveraging its extensive algal cultivation expertise to supply functional ingredients for consumer end-use. "The launch of Solasta™ Astaxanthin coincides with the repositioning of Solix Algredients as a global, B2B supplier of high quality natural ingredients derived from algae," explained James Tuan, Chief Commercial Officer.

Solasta™ will be sold to manufacturers and marketers of dietary supplement and personal care products. "Solasta™ Astaxanthin is the first commercial product in our portfolio of algae-based B2B ingredients," noted Mr. Tuan.

Solasta™ Astaxanthin is manufactured in accordance with industry best practices and guidelines (current Good Manufacturing Practice - GMP) defined by the United States Food and Drug Administration (FDA). Solasta™ meets the strict quality standards set forth in the Astaxanthin Esters Monographs of the Food Chemical Codex and the US Pharmacopeia.

Friday, November 13, 2015

Research finding offers hope for more powerful aspirin-like drugs

Researchers have found that salicylic acid targets the activities of HMGB1, an inflammatory protein associated with a wide variety of diseases, offering hope that more powerful aspirin-like drugs may be developed.

Aspirin is one of the oldest and most commonly used medicines, but many of its beneficial health effects have been hard for scientists and physicians to explain. A recent study conducted by researchers at the Boyce Thompson Institute (BTI), in collaboration with colleagues at Rutgers University and San Raffaele University and Research Institute, shows that aspirin's main breakdown product, salicylic acid, blocks HMGB1, which may explain many of the drug's therapeutic properties. The findings appear Sept. 23, 2015 in the journal Molecular Medicine.

"We've identified what we believe is a key target of aspirin's active form in the body, salicylic acid, which is responsible for some of the many therapeutic effects that aspirin has. This protein, HMGB1, is associated with many prevalent, devastating diseases in humans, including rheumatoid arthritis, heart disease, sepsis and inflammation-associated cancers, such as colorectal cancer and mesothelioma," said senior author Daniel Klessig, a professor at BTI and Cornell University.

Aspirin's pain relieving effects have long been attributed to its ability to block the enzymes cyclooxygenase 1 and 2, which produce prostaglandins--hormone-like compounds that cause inflammation and pain--a discovery that netted its discoverer, John Vane, a Nobel prize. However, the body rapidly converts aspirin to salicylic acid, which is a much less effective inhibitor of cyclooxygenase 1 and 2 than aspirin. Nonetheless, it has similar pharmacological effects as aspirin, suggesting that salicylic acid may interact with additional proteins.

"Some scientists have suggested that salicylic acid should be called 'vitamin S', due to its tremendous beneficial effects on human health, and I concur," said lead author Hyong Woo Choi, a research associate at BTI.

In the current study, researchers discovered the interaction between salicylic acid and HMGB1 by screening extracts prepared from human tissue culture cells to find proteins that could bind to salicylic acid. They identified one of these proteins as HMGB1. These screens have also identified a key suspect in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, plus approximately two dozen additional candidates that have yet to be characterized.

To further investigate the interactions between salicylic acid and HMGB1's role in the body, Klessig worked with Marco Bianchi of San Raffaele University and Research Institute, who initially discovered that HMGB1 is a trigger of inflammation. Using assays that measured the effects of salicylic acid on the recruitment and activation of immune cells, they showed that salicylic acid could block both of these functions at concentrations similar to those found in people on low-dose aspirin.

"We've found that HMGB1 is involved in countless situations where the body confronts damage to its own cells, which occur in many disease conditions. In retrospect, it's almost obvious that a very general anti-inflammatory compound blocks a very general inflammation trigger," said Bianchi.

Klessig also teamed up with biophysicist Gaetano Montelione at Rutgers, The State University of New Jersey, to not only confirm that salicylic acid can bind to HMGB1, but also to identify the salicylic acid binding sites.


Thursday, November 12, 2015

Interim data from long-term extension Tecfidera® (dimethyl fumarate) study



Dimethyl fumarate


In continuation of my update on Dimethyl Fumarate


Biogen (NASDAQ: BIIB) will, this week, present data at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain, demonstrating the efficacy and safety of TECFIDERA® (dimethyl fumarate) across a broad range of people with relapsing-remitting multiple sclerosis (RRMS). The data includes important findings for people in the early stages of the disease (as determined by cognitive testing using paced auditory serial addition test 3), and coincides with recent recommendations on the importance of early treatment highlighted by the MS Society.(1)

A post-hoc analysis of the Phase 3 DEFINE and CONFIRM studies showed that dimethyl fumarate had significant effects on clinical outcomes in RRMS patients who initiated treatment early in their disease course, defined as those patients with a baseline Expanded Disability Status Scale (EDSS) score of ≤2.0 (indicating minimal to no disability). Compared to patients treated with placebo, dimethyl fumarate reduced the adjusted relapse rate (ARR) [95% confidence interval, CI]: 0.132 [0.102, 0.170] vs 0.357 [0.291, 0.438]; 63% reduction; p<.0001) and risk of 12-week confirmed disability progression (0.14 vs 0.24; 40% reduction; p=.0066) over a period of two years.(2)

In an interim analysis of newly diagnosed patients in the ENDORSE long-term extension study (two years in DEFINE or CONFIRM followed by four years in ENDORSE), the ARR for newly-diagnosed patients (diagnosis of multiple sclerosis within 1 year prior to study entry or previously treated with cortico-steroids alone) who started dimethyl fumarate treatment at the beginning of the study (n=144) remained low at 0.14 (0.10–0.19). In those patients who switched from placebo to dimethyl fumarate, the ARR was reduced from 0.26 (0.18–0.37) from the placebo period (years zero to two) to 0.10 (0.06–0.16) when dimethyl fumarate treatment was received (years three to six), representing a 61% reduction of risk; p<0.0001.3



Tuesday, November 10, 2015

Combatting viral and bacterial lung infections with volatile anesthetics: an interview with Dr Chakravarthy



http://www.news-medical.net/


Can you give me a brief overview of bacterial lung infections and why they are so lethal?

If you trace back to the largest pandemics in human history, for example the Spanish Flu, the number of deaths was around 40 million. For flu to truly have an epidemic or pandemic potential, the lethality of the infection itself can't be so high that it doesn't allow for transmissibility. If the flu virus is too lethal than it has a harder time spreading from host to host.


Normal Lung (left) and Lung with Influenza (right). Comparative twin images of normal healthy lung in contrast to lung from a case of influenza showing microscopic disease pathology of flu. © vetpathologist / Shutterstock.com.

When scientists first started to look at what happened during the 1918-1919 pandemic, what we saw was that the major cause of death was not the flu virus but that patients died due to a secondary bacterial pneumonia. So the major question became what was the 1918 flu strain doing that caused people to become susceptible to bacterial super-infections?

So scientists began digging patient samples from the Alaskan permafrost. What they observed was that the primary flu infection caused a significant amount of lung damage in the host without killing them, which then allowed streptococcus pneumonia, the common bacterial super infection, to grow in the lung and cause systemic infection. The body becomes unable to combat this bacterial super infection, which becomes the primary cause of mortality.