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.

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.

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

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

Antiviral agent protects rhesus monkeys from deadly Ebola virus

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. 

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).

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

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

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."

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

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.

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

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.

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.

Solix Algredients introduces Solasta Astaxanthin to B2B marketplace

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.

More at research paper

Research finding offers hope for more powerful aspirin-like drugs

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

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

Details a video ...

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

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

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.

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

L-DOP A drug may delay or prevent age-related macular degeneration

In continuation of my update on L-DOPA

A drug already used safely to treat Parkinson's disease, restless leg syndrome and other movement disorders also could delay or prevent the most common cause of blindness affecting more than 9 million older Americans - age-related macular degeneration (AMD).

Researchers have discovered that patients who take the drug L-DOPA are significantly less likely to develop AMD, and if they do get AMD it's at a significantly older age, according to the study published online Nov. 4 in the American Journal of Medicine. The retrospective study was led by researchers at Marshfield Clinic Research Foundation, University of Arizona, Medical College of Wisconsin, University of Miami, Essentia Health, Stanford University and University of Southern California.

"Research points to this as a pathway to regulate and prevent this most common cause of blindness in adults," said Murray Brilliant, Ph.D., director, Marshfield Clinic Research Foundation Center for Human Genetics, Marshfield, Wisconsin. "Imagine telling patients we potentially have medication that will allow them to see and continue enjoying life, their family and perform every day activities as they age. That is very powerful."

AMD, the No. 1 cause of legal blindness in adults over 60, is a progressive eye condition affecting as many as one in three adults. The disease attacks the macula of the eye, where the sharpest central vision occurs, causing central blindness. This vision is used to drive, read, recognize faces and perform daily tasks. AMD spares the peripheral vision, leaving dim images or black holes at the center of vision.

L-DOPA is a natural by-product of pigmentation and is made in a layer of cells in the back of the eye that functions to promote health and survival of retinal tissues. Researchers asked the question if people taking L-DOPA as a medicine are protected from AMD.

"The obvious question was if the L-DOPA no longer produced was supplemented via pill form, does it have the potential to serve as a preventive medicine against AMD," Brilliant said. "We need more research, but this first step is promising."

L-DOPA drug may delay or prevent age-related macular degeneration

Vraylar (cariprazine) capsules now approved by FDA to treat schizophrenia, bipolar disorder in adults

We know that, Cariprazine (trade name Vraylar, previously known as RGH-188) is an antipsychotic drug developed by Gedeon Richter. It acts as a D2 and D3 receptor partial agonist, with high selectivity towards the D3 receptor.  Positive Phase III study results were published for schizophrenia and mania early 2012, while Phase II studies in bipolar disorder I, and for bipolar depression are in progress.  Action on the dopaminergic systems makes it also potentially useful as an add-on therapy in major depressive disorder  

Rights are currently owned by Gedeon Richter and Actavis. The drug received FDA approval on September 17, 2015.

Now The U.S. Food and Drug Administration today approved Vraylar (cariprazine) capsules to treat schizophrenia and bipolar disorder in adults.

"Schizophrenia and bipolar disorder can be disabling and can greatly interfere with day-to-day activities," said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. "It is important to have a variety of treatment options available to patients with mental illnesses so that treatment plans can be tailored to meet a patient's individual needs."

Schizophrenia is a chronic, severe and disabling brain disorder affecting about one percent of Americans. Typically, symptoms are first seen in adults younger than 30 years of age and include hearing voices or seeing things that are not there, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn.

Bipolar disorder, also known as manic-depressive illness, is another brain disorder that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. The symptoms of bipolar disorder include alternating periods of depression and high, irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior and a decreased need for sleep.

The efficacy of Vraylar in treating schizophrenia was demonstrated in 1,754 participants in three six-week clinical trials. In each of the trials, Vraylar was shown to reduce the symptoms of schizophrenia compared to placebo.

The efficacy of Vraylar in treating bipolar disorder was shown in three three-week clinical trials of 1,037 participants. Vraylar was shown to reduce symptoms of bipolar disorder in each of the trials.

More info video 

Vraylar (cariprazine) capsules now approved by FDA to treat schizophrenia, bipolar disorder in adults

Varubi (rolapitant) approved to prevent delayed phase chemotherapy-induced nausea and vomiting

The U.S. Food and Drug Administration approved Varubi (rolapitant) to prevent delayed phase chemotherapy-induced nausea and vomiting (emesis). Varubi is approved in adults in combination with other drugs (antiemetic agents) that prevent nausea and vomiting associated with initial and repeat courses of vomit-inducing (emetogenic and highly emetogenic) cancer chemotherapy.

Nausea and vomiting are common side effects experienced by cancer patients undergoing chemotherapy. Symptoms can persist for days after the chemotherapy drugs are administered. Nausea and vomiting that occurs from 24 hours to up to 120 hours after the start of chemotherapy is referred to as delayed phase nausea and vomiting, and it can result in serious health complications. Prolonged nausea and vomiting can lead to weight loss, dehydration and malnutrition in cancer patients leading to hospitalization.

"Chemotherapy-induced nausea and vomiting remains a major issue that can disrupt patients' lives and sometimes their therapy," said Amy Egan, M.D., M.P.H., deputy director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research. "Today's approval provides cancer patients with another treatment option for the prevention of the delayed phase of nausea and vomiting caused by chemotherapy."

Varubi is a substance P/neurokinin-1 (NK-1) receptor antagonist. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by certain cancer chemotherapies, particularly in the delayed phase. Varubi is provided to patients in tablet form.

The safety and efficacy of Varubi were established in three randomized, double-blind, controlled clinical trials where Varubi in combination with granisetron and dexamethasone was compared with a control therapy (placebo, granisetron and dexamethasone) in 2,800 patients receiving a chemotherapy regimen that included highly emetogenic (such as cisplatin and the combination of anthracycline and cyclophosphamide) and moderately emetogenic chemotherapy drugs. Those patients treated with Varubi had a greater reduction in vomiting and use of rescue medication for nausea and vomiting during the delayed phase compared to those receiving the control therapy.

Video for more info



Varubi (rolapitant) approved to prevent delayed phase chemotherapy-induced nausea and vomiting

Aristada (aripiprazole lauroxil) extended release injection approved to treat adults with schizophrenia

U.S. Food and Drug Administration approved Aristada (aripiprazole lauroxil) extended release injection to treat adults with schizophrenia. Aristada is administered by a health care professional every four to six weeks using an injection in the arm or buttocks.

Schizophrenia is a chronic, severe and disabling brain disorder affecting about one percent of Americans. Typically, symptoms are first seen in adults younger than 30 years of age and include hearing voices, believing other people are reading their minds or controlling their thoughts, and being suspicious or withdrawn.

"Long-acting medications to treat schizophrenia can improve the lives of patients," said Mitchell Mathis, M.D., director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. "Having a variety of treatment options and dosage forms available for patients with mental illness is important so that a treatment plan can be tailored to meet the patient's needs."

The efficacy of Aristada was demonstrated in part by a 12-week clinical trial in 622 participants. In participants with acute schizophrenia who had been stabilized with oral aripiprazole, Aristada was found to maintain the treatment effect compared to a placebo.

Aristada and other atypical antipsychotic drugs used to treat schizophrenia have a Boxed Warning alerting health care professionals about an increased risk of death associated with the off-label use of these drugs to treat behavioral problems in older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis. Aristada must be dispensed with a patient Medication Guide that describes important information about the drug's uses and risks.

The most common side effect reported by participants receiving Aristada in clinical trials was feeling the urge to move constantly (akathisia).

Video : http://www.rxwiki.com/news-article/aristada-aripiprazole-lauroxil-extended-release-injection-treat-schizophrenia-approved

Aristada (aripiprazole lauroxil) extended release injection approved to treat adults with schizophrenia

FDA approves Lonsurf drug for patients with advanced form of colorectal cancer

In continuation of my update Lonsurf

The U.S. Food and Drug Administration today approved Lonsurf (a pill that combines two drugs, trifluridine and tipiracil) for patients with an advanced form of colorectal cancer who are no longer responding to other therapies.

 (Trifluridine)    (Tipiracil)

"The past decade has brought a new understanding around colorectal cancer, in how we can both detect and treat this often devastating disease," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "But there are many patients who still need additional options, and today's approval is a testament to the FDA's commitment to work with companies to develop new drugs in disease areas where unmet needs remain."

Colorectal cancer is the third most common non-skin cancer in men and women in the U.S., according to the National Cancer Institute. While still the second leading cause of cancer-related death in the U.S., over the past 10 years the number of colorectal cancer cases and related deaths have decreased, due in part to screenings, such as colonoscopies.

FDA approves Lonsurf drug for patients with advanced form of colorectal cancer

Xuriden (uridine triacetate) now approved for patients with hereditary orotic aciduria

The U.S. Food and Drug Administration approved Xuriden (uridine triacetate), the first FDA-approved treatment for patients with hereditary orotic aciduria. Hereditary orotic aciduria is a rare metabolic disorder, which has been reported in approximately 20 patients worldwide.

Hereditary orotic aciduria is inherited from a recessive gene. The disease is due to a defective or deficient enzyme, which results in the body being unable to normally synthesize uridine, a necessary component of ribonucleic acid (RNA). Signs and symptoms of the disease include blood abnormalities (anemia, decreased white blood cell count, decreased neutrophil count), urinary tract obstruction due to the formation of orotic acid crystals in the urinary tract, failure to thrive, and developmental delays.

"Today's approval and rare pediatric disease priority review voucher underscore the FDA's commitment to making treatments available to patients with rare diseases," said Amy G. Egan, M.D., M.P.H., deputy director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research (CDER). "Prior to Xuriden's approval, patients with this rare disorder had no approved treatment options."

The FDA granted Xuriden orphan drug designation because it treats a rare disease. Orphan drug designation provides financial incentives, like clinical trial tax credits, user fee waivers, and eligibility for market exclusivity to promote rare disease drug development. Xuriden was also granted priority review. An FDA priority review provides for an expedited review of drugs for serious diseases or conditions that may offer major advances in treatment. The manufacturer of Xuriden was granted a rare pediatric disease priority review voucher – a provision that encourages development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

Xuriden is an orally administered product intended to replace uridine. Xuriden is approved as oral granules that can be mixed with food or in milk or infant formula, and is administered once daily.

The safety and effectiveness of Xuriden were evaluated in a single arm, six-week, open-label trial in four patients with hereditary orotic aciduria, ranging in age from three to 19 years of age, and in a six-month extension phase of the trial. The study assessed changes in the patients' pre-specified hematologic parameters during the trial period. At both the six-week and six-month assessments, Xuriden treatment resulted in stability of the hematologic parameters in all four clinical trial patients. The safety and effectiveness of uridine replacement therapy were further supported by case reports from the published literature.

Xuriden (uridine triacetate) now approved for patients with hereditary orotic aciduria

Everolimus, 177Lu-dotatate extend neuroendocrine tumour PFS

 

Positive progression-free survival (PFS) results from the RADIANT-4 and NETTER-1 trials extend the armamentarium for physicians treating patients with neuroendocrine tumours (NETs).

The studies, indicating efficacy for the mTOR inhibitor everolimus and the peptide receptor radionuclide therapy lutetium (Lu)177-dotatate, respectively, were presented at the European Cancer Congress held in Vienna, Austria.

The primary endpoint of PFS in the RADIANT-4 trial, as determined by central radiological review, was 11.0 months in the 205 patients with non-functional NETs of the gastrointestinal tract or lung who were randomly assigned to receive everolimus 10 mg/day compared with 3.9 months in the 97 patients given placebo, with a significant hazard ratio (HR) of 0.48.

The “robust benefit” was confirmed by investigator assessment, with PFS of 14.0 months versus 5.5 months in the everolimus and placebo groups, and a significant HR of 0.39.

The first planned interim overall survival analysis showed a 36% reduction in the risk of death in favour of everolimus and, although this was not statistically significant, the researchers believe that analysis of mature data in 2016 may show a significant result.

“Although we knew from previous studies that everolimus could delay the growth of pancreatic NETs, this is the first time we have been able to conclusively show that it is effective in other NET sites”, said James Yao, from the University of Texas MD Anderson Cancer Center in Houston, USA, and RADIANT-4 co-investigators in a press release.

Everolimus, 177Lu-dotatate extend neuroendocrine tumour PFS

2-year advanced melanoma survival benefit with dabrafenib, trametinib combination

Updated results from the COMBI-v trial show significantly improved overall and progression-free survival (OS, PFS) with first-line dabrafenib plus trametinib compared with vemurafenib in patients with advanced melanoma.

The findings of the phase III trial comprising patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma were presented at the European Cancer Congress in Vienna, Austria, by Caroline Robert, from the Institut Gustave Roussy in Paris, France.

A previous interim analysis with a median follow-up of 11 months showed a significant improvement in OS with dabrafenib and trametinib, explained Robert in her presentation, so much so that the trial was terminated early and patients in the vemurafenib group were allowed to crossover.

In this most recent analysis, the 352 patients randomly assigned to receive the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib had a median OS of 25.6 months. This was not only significantly longer than the 18.0 months observed for the 352 participants given the BRAF inhibitor vemurafenib, but also the “longest ever reached” in a randomised phase III trial in this patient population, said Robert.

And after a median follow-up of 19 months, the 2-year survival rate was significantly higher for the dabrafenib plus trametinib group than for the vemurafenib group, at 51% versus 38%.

Median PFS was also significantly longer, with corresponding times of 12.6 and 7.3 months, and overall response rate and duration of response were similarly improved in the dual therapy compared with the monotherapy arm, at 66% versus 53% and 13.8 versus 8.5 months, respectively.

The incidence of all-grade adverse events continued to be high during the additional follow-up period, with pyrexia (55%) most common in the combination group and arthralgia (52%) in the vemurafenib group, but Robert said this was not surprising.

2-year advanced melanoma survival benefit with dabrafenib, trametinib combination

Neurocrine Biosciences announces positive data from NBI-98854 Phase III trial in tardive dyskinesia

Neurocrine Biosciences, Inc. announced that NBI-98854, a highly selective small molecule VMAT2 inhibitor, showed a statistically significant reduction in tardive dyskinesia during the six weeks of placebo-controlled treatment in the Kinect 3 clinical trial. This Phase III trial included moderate to severe tardive dyskinesia patients with underlying schizophrenia, schizoaffective disorder, bipolar or major depressive disorder.

The pre-specified primary efficacy endpoint was the change-from-baseline in the Abnormal Involuntary Movement Scale (AIMS) at Week 6 in the 80mg once-daily dosing group compared to placebo as assessed by central blinded video raters. The AIMS ratings at Week 6 for the 80mg once-daily NBI-98854 intention-to-treat (ITT) population was reduced 3.1 points (Least-Squares Mean) more than placebo (p<0.0001).

"We are very pleased with the outstanding efficacy and side effect profile demonstrated by NBI-98854 in the Kinect 3 study. The efficacy data from this pivotal Phase III study completes our placebo-controlled dataset for NBI-98854 in tardive dyskinesia," said Kevin C. Gorman, President and Chief Executive Officer of Neurocrine. "We will now turn our focus to completing the open-label safety portion of the studies in tardive dyskinesia patients and compiling the data for both doses of NBI-98854 to be included in the New Drug Application we intend to file with the FDA in 2016."

"The results of this Kinect 3 study demonstrate the potential of NBI-98854 to be a safe and effective treatment for patients suffering from the debilitating effects of tardive dyskinesia and we look forward to sharing additional details of this important study at upcoming scientific meetings starting in mid-2016," said Christopher F. O'Brien, Chief Medical Officer of Neurocrine. "We want to thank the trial participants and investigators who contributed to this successful placebo-controlled portion of the Kinect 3 study and we look forward to continuing our work with them in the open-label safety assessment of NBI-98854 in patients suffering from tardive dyskinesia, as well as completing the initial Tourette syndrome study later this year."

Neurocrine Biosciences announces positive data from NBI-98854 Phase III trial in tardive dyskinesia

AcelRx Pharmaceuticals, Inc : Sufentanil

AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of acute pain, today provided a regulatory update on Zalviso™ (sufentanil sublingual tablet system) intended for the management of moderate-to-severe acute pain in adult patients in the hospital setting. The company has received formal minutes of the telephonic meeting held in early September 2015, with the Division of Anesthesia, Analgesia, and Addiction Products of the Food and Drug Administration (FDA). As reflected in the minutes, the Division restated at the meeting a request for clinical data to complement other data AcelRx has developed to assess the overall performance of the Zalviso device.

The company is planning to submit a protocol to the Division for a clinical study in post-operative patients designed to evaluate the effectiveness of changes made to enhance product performance. AcelRx expects to be ready to initiate the study in the first quarter of 2016, and likely will await comments on the protocol from the Division. The company will be prepared to work with the FDA to facilitate the timely study initiation.

"We have been preparing a clinical study to investigate the use of Zalviso in a more diverse post-surgical population than in our original Phase 3 studies," stated Pamela P. Palmer, MD, PhD, chief medical officer of AcelRx, "so we are modifying the design of this study to include endpoints that we believe will address the Division's concerns."

AcelRx Pharmaceuticals, Inc : Sufentanil

FDA grants Breakthrough Therapy Designation to Lilly's abemaciclib for treatment of metastatic breast cancer

Eli Lilly and Company (NYSE: LLY)   announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to abemaciclib, a cyclin-dependent kinase (CDK) 4 and 6 inhibitor, for patients with refractory hormone-receptor-positive (HR+) advanced or metastatic breast cancer. This designation is based on data from the breast cancer cohort expansion of the company's Phase I trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. Patients in this cohort had received a median of seven prior systemic treatments. These data were presented at the San Antonio Breast Cancer Symposium in 2014.

According to the FDA, Breakthrough Therapy Designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.

FDA grants Breakthrough Therapy Designation to Lilly's abemaciclib for treatment of metastatic breast cancer

New drug may prevent malaria in pregnant women

Researchers at LSTM, working with colleagues of the Centres for Disease Control and Prevention (CDC) in Kenya and USA, and from the Kenya Medical Research Institution have found that a new drug may be more effective at preventing malaria in pregnant woman, especially where there is resistance to the current treatments.

LSTM's Professor Feiko ter Kuile, who heads the Malaria in Pregnancy (MiP) Consortium, was senior author on the study which has been published today in the journal The Lancet. The study evaluated the efficacy and safety of two alternative strategies in comparison to the standard treatment recommended for the prevention of malaria in 1546 HIV-negative pregnant women in western Kenya.

Malaria infection during pregnancy is a significant health problem to both the mother and the unborn child. It has been associated with chronic anaemia in the mother, and with loss of the pregnancy due to miscarriages or stillbirths and with low birth weight in pregnancies that result in livebirths, which in turn results in an increased risk of infant death. The World Health Organization (WHO) currently recommends that women in areas of stable malaria transmission receive intermittent preventative treatment in pregnancy (IPTp) with the antimalarial drug sulfadoxine-pyrimethamine (SP). Sulfadoxine-pyrimethamine is currently the only antimalarial drug that is recommended by WHO for this IPTp strategy, however high levels of resistance from the malaria parasite to this drug threatens its efficacy.

New drug may prevent malaria in pregnant women

Two studies identify promising new anti-retroviral strategy to combat HIV-1

A pair of studies by researchers at the University of Massachusetts Medical School, the University of Trento in Italy, and the University of Geneva in Switzerland, point to a promising new anti-retroviral strategy for combating HIV-1. The two studies, published online in Nature, show that the host cell membrane proteins SERINC5 and SERINC3 greatly reduce the virulence of HIV-1 by blocking the ability of the virus to infect new cells. HIV-1 encodes a protein called Nef that counteracts the SERINCs. New drugs that target the HIV-1 protein Nef would permit the SERINC proteins to inactivate the virus. The papers will appear in the October 8 issue of Nature.

"It's amazing, the magnitude of the effect that these proteins have on infectivity," said Jeremy Luban, MD, the David J. Freelander Professor in AIDS Research and professor of molecular medicine at UMass Medical School. "The SERINC proteins reduce the infectivity of HIV-1 virions by more than 100-fold."

Heinrich Gottlinger, professor of molecular, cell and cancer biology at UMass Medical School said, "The ability of HIV to inhibit these SERINC proteins has a profound impact on its capacity to infect other cells. Disrupting this mechanism could be a very powerful strategy for treating HIV and similar viruses that express the Nef protein."

The two studies, each done independently, used completely different, yet complementary, methodologies to unravel the complex interaction between the HIV-1 protein Nef and the cell surface membrane proteins SERINC5 and SERINC3, both of which are expressed in the immune system's T cells. Dr. Luban, working with former members of his lab, Massimo Pizzato, PhD, now of the University of Trento in Italy, and Federico Santoni of the University of Geneva in Switzerland, performed massively parallel sequencing on 31 human cell lines that differed in terms of the magnitude of dependence on Nef for HIV-1 replication. Independently, Dr. Gottlinger approached the problem biochemically. Conducting proteomic analysis of purified virions, he was able to identify host cell proteins that Nef regulated.

Two studies identify promising new anti-retroviral strategy to combat HIV-1

Two studies identify promising new anti-retroviral strategy to combat HIV-1

Experimental drug shows promise in mice with multiple sclerosis

An experimental drug originally identified in a National Cancer Institute library of chemical compounds as a potential therapy for brain and basal cell cancers improves the symptoms of mice with a form of the debilitating neurological disorder multiple sclerosis (MS), according to new research from NYU Langone Medical Center.

The experimental drug employed by the NYU Langone team of neuroscientists is called GANT61. It blocks the action of a key protein, Gli1, which is involved in so-called sonic hedgehog signaling, a biological pathway closely tied to neural stem cell development and the growth of some cancers, and whose signaling is raised in tissue samples taken from brain lesions in patients with MS.

A report describing the findings is being published in the journal Nature online Sept. 30.

In the study, mice with chemically damaged brain myelin were given daily doses of GANT61 for one month. Results showed that mice that received the drug had 50 percent more myelin at the end of treatment than did untreated mice. Myelin is the nerve-protecting sheath whose degradation is a principal cause of MS.

Experimental drug shows promise in mice with multiple sclerosis

Tris Pharma announces launch of generic TUSSIONEX

Tris Pharma, a specialty pharmaceutical company that develops innovative drug delivery technologies, announced the launch of Tris-labeled generic TUSSIONEX®, an extended-release suspension containing hydrocodone polistirex and chlorpheniramine polistirex.

Tussionex®, originally approved in the early 1980's, had no generic competition until 2010 when Tris Pharma's generic product entered the market under an exclusive distribution agreement with Par Pharmaceuticals. Under the terms of the distribution agreement, Par had the exclusive right to market Tris Pharma's hydrocodone polistirex and chlorpheniramine polistirex ER oral suspension for a five year period ending September 30, 2015. With the conclusion of the five year term, the rights have reverted back to Tris and as of October 1, 2015, hydrocodone polistirex and chlorpheniramine polistirex ER Suspension in 115ml and 473 ml bottles (compare to Tussionex®) will be marketed and distributed by Tris Pharma's generic business.

Tris Pharma announces launch of generic TUSSIONEX