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