FDA Approves Moxidectin for the Treatment of River Blindness

Medicines Development for Global Health (MDGH) and the World Health Organisation Special Programme for Research and Training in Tropical Diseases (TDR) announced today that the United States (U.S.) Food and Drug Administration (FDA) approved moxidectin 8 mg oral for the treatment of river blindness (onchocerciasis) in patients aged 12 years and older1. The FDA has also awarded MDGH a priority review voucher (PRV).

River blindness is caused by a parasitic worm, Onchocerca volvulus. The disease manifests as severe itching, disfiguring skin conditions and visual impairment, including permanent blindness, caused by the worm’s larvae (microfilariae). The approval of moxidectin was based on data from two randomized, double blind, active controlled clinical studies2,3. Each study met its respective primary endpoints, showing a statistically significant superiority of moxidectin over the current standard of care, ivermectin, in suppressing the presence of the microfilariae in skin. Full results from the Phase III study were published in the Lancet in January 20183 and a safety summary is provided below.

“FDA approval is a momentous achievement for any biopharmaceutical company, but it is a particularly rare and exciting event in the neglected diseases setting” said Mark Sullivan, Founder and Managing Director of MDGH. “It takes a broad community to develop a new medicine. FDA approval represents decades of work by thousands of scientists, disease control specialists, expert advisors, community health workers, funders and study participants. We particularly acknowledge the US$13 million investment from the Global Health Investment Fund (GHIF) as well as the extraordinary persistence and dedication of the team at TDR, without whom this would not have happened.”

TDR (the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases) was instrumental in the development of moxidectin. “We are delighted about the FDA’s decision,” says TDR Director John Reeder. “It is a milestone toward the river blindness endgame and our objective to enable African countries to integrate moxidectin into their elimination strategies.”

This approval is the result of a paradigm-changing approach to the development of new medicines for neglected diseases, enabled by the PRV program. “As neglected tropical diseases are endemic in low and middle-income countries, there are limited markets for medicines. Therefore, finding investors willing to support development in these diseases is extremely difficult” added Mark Sullivan. “However, the introduction of the FDA’s neglected diseases PRV program has created a market around neglected diseases.“

The PRV legislation was designed to encourage development of new drug and biological products for neglected diseases. The PRV, a saleable item, permits the holder to accelerate the review of a new drug application (NDA) from the standard 10 months to 6 months. This time saving has significant value to the pharmaceutical industry, thus creating an indirect market for neglected disease treatments.

Dr. Reeder added, “This voucher to MDGH exemplifies the original spirit of the programme – to create incentives for research and development in neglected diseases.”

MDGH is the first not-for-profit company to register a medicine through the tropical disease PRV program. “This is exactly what we had in mind when we proposed the PRV program,” said Duke University’s Professor David Ridley, an author of the 2006 paper on which the voucher scheme is based. “The voucher incentive helped Medicines Development for Global Health attract funding to complete testing and registration for a drug that had been on the shelf. I’m delighted that the voucher program is playing a role in treating patients with river blindness, and one day eliminating the disease.”

“Achieving FDA approval is a critically important milestone for moxidectin, but our work to bring this medicine to those who need it most continues in earnest,” concluded Mr. Sullivan. “MDGH plans to provide the community with additional data, including data in younger children. We are here for the full journey – we have committed our skills and resources to play our part in ridding the world of this disabling disease.”

https://en.wikipedia.org/wiki/Moxidectin

Want to Avoid Type 2 Diabetes? Eat More Whole Grains

It may seem counter intuitive, but eating bread, pasta and cereal may actually help prevent type 2 diabetes, as long as those foods are made from whole grains, new research suggests.

The study found that each serving of whole-grain foods per day was linked to as much as an 11 percent drop in the risk of type 2 diabetes.

"Whole grains appear to play an important role in the prevention of type 2 diabetes, and choosing whole grains over refined grains is highly recommended," said study author Cecilie Kyro. She is a post-doctoral researcher at the Danish Cancer Society Research Center in Copenhagen.

Kyro added that, in addition to preventing type 2 diabetes, there is evidence that whole grains can help prevent heart disease and colon cancer.

More than 30 million Americans have diabetes, and most have type 2 diabetes, according to the American Diabetes Association (ADA). People with type 2 diabetes don't use the hormone insulin efficiently.

Insulin normally ushers blood sugar into cells to be used as energy. But some people are resistant to the effects of insulin, and then more and more insulin is needed to do the same job. Eventually, the insulin-producing cells in the pancreas can't keep up with the demand, and blood sugar levels rise, resulting in type 2 diabetes, according to the ADA.

Lifestyle factors, such as diet and exercise, are known to play a role in type 2 diabetes. In the latest study, researchers wanted to see what role specific whole grains played in type 2 diabetes.

To do this, they reviewed diet information from more than 55,000 people, aged 50 to 65, in Denmark. On average, the group was slightly overweight.

Overall, about 7,400 people were diagnosed with type 2 diabetes during the study's average 15-year follow-up.

The study volunteers completed food diaries. From these food diaries, the researchers calculated how many grams of whole grains each person ate daily.

The investigators found that for every serving of whole-grain food, the risk of type 2 diabetes dropped by 11 percent for men and 7 percent for women.

In women, only wheat and oats seemed to reduce the risk of diabetes. But for men, all whole grains -- wheat, rye and oats -- were linked to a lower risk of the blood sugar disorder. Kyro said this difference may just be a statistical anomaly because fewer women developed diabetes.

She added that all whole-grain products can be recommended for preventing type 2 diabetes in both men and women.

Exactly how whole grains help prevent type 2 diabetes isn't clear from this study. Because it's an observational study, it isn't designed to prove a cause-and-effect relationship.

Still, the scientists suspect that there may be several reasons why whole grains could be protective, including reduced blood sugar secretion after a meal.

Registered dietician Samantha Heller said the findings fall in line with previous research.

"People who consume whole grains have lower risks of type 2 diabetes, as well as inflammation, coronary heart disease and cancer," she said. In addition, a diet including whole grains also helps with weight management and may improve digestive health.

"Whole grains contain fiber, vitamins, minerals, protein and phytonutrients, all of which play important roles in maintaining a healthy body. Dietary fiber decreases insulin resistance, after-meal blood sugar spikes and decreases inflammation, all of which may contribute to its beneficial effects on type 2 diabetes," Heller explained. (Phytonutrients are nutrients from plant sources.)

Kyro said one serving of whole grain contained 16 grams of whole grain. That can vary depending on the type or brand of a product, but 16 grams is approximately one slice of whole-grain bread, she said.

Heller said that U.S. dietary guidelines recommend three to four servings of whole grains a day. A serving is one slice of bread, one-cup of ready-to-eat cereal or 1/2-cup cooked rice, pasta or cereal. She said those recommendations are for people who are sedentary. If you're more active, you may need more grains each day.

Findings from the study were published in the September issue of The Journal of Nutrition.

New Drug Fingolimod (Gilenya) Could Help Kids With MS

In continuation of my update on Fingolimod

Researchers say the first drug for children with multiple sclerosis vastly outperformed another common MS medication in a new clinical trial.

Fingolimod(Gilenya) reduced relapse rates by 82 percent in patients aged 10 to 17 compared with interferon beta-1a, a drug commonly used to slow the progression of the degenerative nerve disease.

Nearly 86 percent of children on fingolimod remained relapse-free after two years of treatment, compared with only 39 percent of children taking interferon beta-1a, researchers reported.

"I do recommend doctors consider using fingolimod as first-line treatment in pediatric MS," said lead researcher Dr. Tanuja Chitnis, director of the Partners Pediatric MS Center at the Massachusetts General Hospital for Children.

Based on results from this clinical trial, the U.S. Food and Drug Administration in May approved the use of fingolimod in children, Chitnis said.

That makes fingolimod "the first drug approved in the U.S. for pediatric MS," Chitnis said.

Other drugs like interferon beta-1a are used in children, but their use is considered "off-label," said Bruce Bebo, executive vice president of research for the National MS Society.

"We consider this a major development, a major milestone in the MS treatment landscape," Bebo said of fingolimod's approval for use in children.

Multiple sclerosis occurs when the immune system turns on the nervous system and attacks the protective sheath that covers nerve fibers, disrupting communication between the brain and the rest of the body.

MS causes vision problems, numbness or tingling, tremors, slurred speech and fatigue in patients. If left unchecked, it eventually will make it difficult for the person to walk.

Fingolimod is believed to treat MS by suppressing blood levels of lymphocytes, white blood cells that promote the immune system attack on nerve fibers, said Bebo, who was not involved with the trial.

"It slows down dramatically the pathways that lead to relapsing MS," Bebo explained.

The FDA approved fingolimod for use in adults in 2010, and the new trial is part of agency requirements to test new drugs in pediatric patients, Bebo said.

The peak age of MS onset is the 30s and 40s, but about 3 to 5 percent of patients develop symptoms of the disease in childhood, researchers said in background information.

For the clinical trial, 215 young patients were randomly assigned to take either fingolimod, which is an oral drug, or interferon beta-1a, which is injected.

Fingolimod kept MS from progressing in more than 8 out of 10 children taking the drug for two years, more than double the percentage of kids taking interferon beta-1a.

Fingolimod also slowed the development of lesions on the brain and spinal cord, a hallmark of MS. The rate of new or newly enlarged lesions discovered through MRI was 4.4 with fingolimod and 9.3 with interferon beta-1a.

Both drugs carried a high risk of adverse events, 89 percent with fingolimod and 95 percent with interferon beta-1a.

Serious adverse events occurred in about 17 percent of patients taking fingolimod, and included seizures, infection and low white blood cell counts.

"The ultimate decision is based on a clear benefit-risk discussion between the physician and family-patient. A careful review of potential side effects and monitoring is required," Chitnis said.

The findings were published Sept. 12 in the New England Journal of Medicine.

https://en.wikipedia.org/wiki/Fingolimod

Nocdurna (desmopressin acetate) Approved by FDA as First Sublingual Tablet to Treat Nocturia due to Nocturnal Polyuria

The U.S. Food and Drug Administration (FDA) granted Ferring Pharmaceuticals Inc. approval to market Nocdurna, the first sublingual tablet for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least two times per night to void. The formulation of the sublingual tablet and sex-specific dosing was demonstrated to be effective in reducing nighttime trips to the bathroom in adults 18 years and older.

Nocturnal polyuria, a disease of the kidneys, is the most common underlying cause of nocturia, which can affect adults at every age. It occurs when a person has insufficient nocturnal vasopressin, causing an overproduction of urine in the kidneys at night.2 Unlike treatments that target the bladder or prostate, Nocdurna acts on receptors in the kidney to absorb more fluid and produce less urine during the night while patients sleep. Nocdurna was approved with a boxed warning because it can cause hyponatremia.

“Millions of individuals across the country face nocturia each night, many of whom suffer the daytime consequences of fatigue and lost productivity,” stated Jeffrey P. Weiss, MD, FACS, Professor and Chairman of Urology, State University of New York (SUNY) Downstate Medical Center. “Nocdurna offers the first sublingual tablet that can target the source of nighttime urination, the kidney, and effectively reduce the number of times patients have to wake up each night to urinate.”

“For more than a decade, Ferring has provided innovative treatments for patients suffering from nocturia in many other countries around the world,” said Paul Navarre, CEO, Ferring US. “Following today’s FDA approval, we are delighted to make Nocdurna available as an option for US healthcare providers and their patients.”

The FDA approval of Nocdurna is based on three double-blind placebo-controlled, multi-center, randomized trials and one open-label extension trial of up to three years in patients 18 years and older. Included in the clinical trials were patients also taking OAB or BPH medications. The co-primary endpoints in studies 1 and 2 were the change in number of nighttime voids compared to baseline, and the percentage of patients who achieved at least a 33% reduction from baseline in the mean number of nighttime voids during three months of treatment. Clinical trials demonstrated an average reduction of nocturnal voids of 52% in women (n=118) and 43% in men (n=102) relative to mean baseline (reduction of 1.5 and 1.3 voids respectively). The mean baseline was 2.9 for women and 3.0 for men. Also, 78% of women and 67% of men receiving NOCDURNA achieved a 33% reduction in mean number of nocturnal voids over a three month period compared to baseline.1

Nocdurna can cause hyponatremia. Severe hyponatremia can be life-threatening, leading to seizures, coma, respiratory arrest, or death. Nocdurna is contraindicated in patients at increased risk of severe hyponatremia, such as patients with excessive fluid intake, illnesses that can cause fluid or electrolyte imbalances, and in those using loop diuretics or systemic or inhaled glucocorticoids. Ensure the serum sodium concentration is normal before starting or resuming Nocdurna. Measure serum sodium within 7 days and approximately 1 month after initiating therapy, and periodically during treatment. Monitor serum sodium levels more frequently in patients 65 years of age and older and in patients at increased risk of hyponatremia. If hyponatremia occurs, Nocdurna may need to be temporarily or permanently discontinued.

Research does not confirm antidiabetic action of natural fatty acid derivatives

A research consortium between the healthcare company Sanofi and Johannes Gutenberg University Mainz (JGU) investigated the antidiabetic action of certain natural fatty acids, so-called FAHFAs, which US-American scientists had reported in 2014. For some of these compounds, e.g. 5-PAHSA and 9-PAHSA, elevated levels were found in mice which overexpressed the glucose transporter Glut4. This transporter is controlled by insulin and causes the uptake of blood glucose in particular into muscle cells. It had been reported that both PAHSA isomers occur in food and are also produced by human cells. Diabetics have lower blood levels of these compounds than healthy individuals. When mice were fed with a FAHFA-enriched diet, their blood glucose levels were found to decrease and insulin was released.

These results published in a prominent journal caused a stir among scientists as they suggested a new point of attack in the fight against a widespread disease. Chemists under guidance of Professor Till Opatz from Mainz University synthesized the stereoisomers of 5- and 9-PAHSA and sent them to their colleagues at Sanofi in Frankfurt for biological testing. In some of the tests, rudimentary metabolic changes could be detected but the overall effect of the compounds was sobering: none of these molecules was able to achieve positive effects on clearly defined endpoints in metabolism.

The results of the researchers from Frankfurt and Mainz recently appeared in Cell Metabolism, a highly renowned international scientific journal. Now the German scientists hope for a constructive discussion on the discrepancy between both studies resulting in a better understanding of the disease models.

The current publication demonstrates the successful collaboration between a university and a research-active healthcare company in a highly relevant area of basic research in biomedicine. It underlines the importance of verification of scientific results and their disclosure.

Lenabasum has acceptable safety and tolerability in diffuse cutaneous systemic sclerosis

The results of an open label extension of a phase II study presented today at the     Annual European Congress of Rheumatology (EULAR 2018) demonstrate that lenabasum ontinues to have acceptable safety and tolerability in diffuse cutaneous systemic sclerosis (dcSSc) with no severe or serious adverse events (AE).

"There is a critical unmet need for safe and effective therapeutics for patients with dcSSc," said Professor Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR. "These results demonstrate a significant step forward in the clinical development of a potentially impactful treatment for people suffering with this devastating disease."

Systemic sclerosis is a rare but serious autoimmune disease which causes hardening and swelling of the skin, as well as joint pain, digestive problems, lung disease, and sometimes problems with the heart and kidneys. The disease occurs in around 30 people per million population per year. The diffuse cutaneous subtype (dcSSc) is even rarer, affecting just one in every four people with the disease. It is linked with early damage to internal organs, as well as painful skin thickening that quickly gets worse. Only half of people diagnosed with dcSSc will survive for 10 years or more.

Medicines for dcSSc are very limited, immunosuppressants are sometimes used although there have been relatively few trials in dcSSc patients specifically because the disease is so rare and difficult to research.

"Our results are very encouraging and reinforce the positive findings from the double-blinded placebo-controlled part of the study with regard to safety and tolerability," said Robert Spiera, M.D., Director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, Weill Cornell Medical College in New York City and principal investigator. "We look forward to continuing our investigations to assess the role of lenabasum as a new treatment option for patients with dcSSC."

Lenabasum (JBT-101) is a selective cannabinoid receptor type 2 agonist that activates resolution of innate immune response in humans and reduces inflammation and fibrosis in animal models of SSc. It is a synthetic, oral, non-immunosuppressive small molecule.

The results of the initial phase II trial demonstrated that lenabasum had acceptable safety and tolerability in dcSSc and demonstrated consistent evidence of clinical benefit. In addition, changes in gene expression were shown to be consistent with biologic effects of lenabasum on pathways relevant to SSc.

Thirty-six patients, who completed the phase II trial, enrolled into the one year open-label extension (OLE) to receive lenabasum 20mg twice a day. Results suggested improvement in multiple efficacy outcomes measured both from the start of the original study and the OLE. In the 25 subjects who completed a year in the OLE, the mean improvements from the study start included an improvement in ACR CRISS score* by 56%. There was also a reduction in modified Rodnan Skin Score, HAQ-DI†, Physician Global Assessment, and 5-D Itch Questionnaire by 8.6, 0.14, 0.9, and 2.3 respectively. Forced vital capacity percentage predicted was stable from study start with mean change of 0.4%.

The mean duration of treatment in the OLE was 45 weeks with 19 patients completing 60 weeks of treatment. Three subjects discontinued the trial, two due to AEs and one withdrew consent. AEs occurred in 33/36 subjects in the OLE, however only seven had AEs related to lenabasum (none of which were severe). In total, one subject had an AE considered life threatening, three severe, 21 moderate, and eight mild. One subject developed renal crisis involving two severe and one life-threatening/serious AE (deemed unrelated to lenabasum). Most common AEs across all subjects were upper respiratory tract infection (22%), urinary tract infection (14%), diarrhea (11%), skin ulcers (11%), and mild intermediate dizziness (8%).

An international phase III clinical trial of lenabasum has been initiated with results expected in the first half of 2020.

Drug used to treat myelofibrosis can awaken ‘dormant’ lymphomas in the bone marrow

"Using bone marrow biopsies taken right at the start of the disease, we were able to show that primordia of lymphoma were present in the form of a B-cell clone," explain Heinz Gisslinger and Ulrich Jäger from the Division of Hematology/Hemostatsology of MedUni Vienna's Department of Medicine I. 16% of myelofibrosis patients were found to have dormant aggressive lymphoma. In approximately 6% of these patients, it then erupts when stimulated by the administration of JAK2 inhibitors.

According to the hematologist, it is possible to detect dormant lymphomas, if they are actively sought using sensitive, molecular biological techniques. "This is therefore the best predictive tool. It enables us to filter out the relevant 16%, categorize them and identify them as high-risk patients prior to treatment with JAK2 inhibitors."

The findings of the hematologists working with MedUni Vienna's Division of Medical-Chemical Laboratory Diagnostics and Clinical Pathology were substantiated by researchers at Vetmeduni Vienna, led by Veronika Sexl. They demonstrated in a mouse model that mice who have had bone marrow transplants likewise developed lymphomas. Says Jäger: "The findings from Vetmeduni Vienna fitted together with ours like a piece of a jigsaw puzzle." Moreover, two individual cases from Paris, from international collaborative partner Hôpital Saint-Louis, backed up the conclusions of the Vienna study, which has now been published in the prestigious journal "Blood", where it was also featured in the editorial.

"This multilateral collaboration is a perfect example of how open the research landscape has generally become and how important the reciprocal exchange of data is in medicine," says Jäger. This is also the direction taken by the next step of this project: a start is already being made on collecting international cases and associated data, in order to further enhance drug safety, and researchers are working closely with the pharmaceutical companies who produce these standard drugs. "Our findings represent a paradigm shift and improve the safety of this class of drugs," emphasize Sexl and Jäger.

"I am delighted by the quick, efficient and groundbreaking bridge between the mouse model and the clinical findings that we have succeeded in forming in this case. The basic research, preclinical and clinical work have all fitted together perfectly," adds Sexl.

Ref : https://www.meduniwien.ac.at/web/en/about-us/news/detailsite/2018/news-im-juni-2018/standard-myelofibrosis-drug-can-awaken-dormant-lymphoma/

Eating plant-based diet can reduce risk for heart problems in people with type 2 diabetes

Plant-based diets improve glycemic control, lead to weight loss, and improve cholesterol in people with type 2 diabetes, according to a new review published in the journal Clinical Nutrition.

Researchers reviewed nine randomized controlled trials that assessed the effectiveness of vegan and vegetarian diets for diabetes patients. The results show that those who ate a plant-based diet lowered their cholesterol, lost weight, lowered HbA1c levels, and improved other cardiometabolic risk factors when compared to those who ate a nonvegetarian diet.

More than 100 million Americans currently have diabetes or prediabetes. Those with diabetes are two to four times more likely to die from cardiovascular disease than those who do not have diabetes.

"The link between diabetes and cardiovascular disease is strong. Sixty to seventy percent of people who have type 2 diabetes die of heart disease," says study co-author Hana Kahleova, M.D., Ph.D., director of clinical research at the Physicians Committee for Responsible Medicine. "The good news is that this study shows that the same simple prescription--eating a plant-based diet--can reduce our risk for heart problems and improve type 2 diabetes at the same time."

The study authors suggest that plant-based diets, which center on fruits, vegetables, grains, and legumes, benefit both glycemic control and cardiovascular health, because they are low in saturated fat, rich in phytochemicals, high in fiber, and often rich in low-glycemic fruits and vegetables.

Previous controlled trials and prospective cohort studies have shown that a plant-based dietary pattern is associated with a lower risk of coronary heart disease, type 2 diabetes, obesity, hypertension, cardiovascular mortality, and all-cause mortality.

Ref : https://www.elsevier.com/books/vegetarian-and-plant-based-diets-in-health-and-disease-prevention/mariotti/978-0-12-803968-7#

FDA Approves Mircera for Anemia Associated with Chronic Kidney Disease in Pediatric Patients on Dialysis

Food and Drug Administration approved methoxy polyethylene glycol-epoetin beta (Mircera, Vifor Pharma Inc.) for the treatment of pediatric patients 5 to 17 years of age on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA.

Approval was based on data from an open-label, multiple dose, multicenter, dose-finding trial (NCT00717366) in 64 pediatric patients (ages 5 to 17 years) with CKD on hemodialysis and had stable hemoglobin (Hb) levels while previously receiving another ESA (epoetin alfa/beta or darbepoetin alfa). Patients were administered Mircera intravenously once every 4 weeks for 20 weeks. After the first administration of Mircera, dosage adjustments were permitted to maintain target Hb levels.

Efficacy was based on maintaining Hb levels within target levels in the above clinical trial, and also from extrapolation from trials of Mircera in adult patients with CKD. The safety findings observed in pediatric patients were consistent with those previously reported in adults.

For conversion from another ESA, Mircera is dosed intravenously once every 4 weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion. Full prescribing information is available at Mircera PI.

FDA approves combination of Venclexta and Rituxan for lymphocytic leukemia treatment

   

                   

  

Venclexta® (venetoclax)                                           Rituxan® (rituximab)     

In continuation of my update on Venclexta® (venetoclax)  and Rituxan® (rituximab)

Genentech, a member of the Roche Group, announced today that the U.S. Food and Drug Administration (FDA) has approved Venclexta® (venetoclax) in combination with Rituxan® (rituximab) for the treatment of people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy. Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

"We are pleased that this approval makes Venclexta, a first of its kind targeted therapy, available for more people with chronic lymphocytic leukemia whose disease has returned after previous treatment," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing compared to a standard-of-care therapy."

The approval of Venclexta plus Rituxan for people with previously treated CLL is primarily based on the results of the Phase III MURANO study, which were published online in the New England Journal of Medicine in March 2018 and presented at the American Society of Hematology Annual Meeting in December 2017. The results showed that a fixed duration of treatment with Venclexta plus Rituxan significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 81 percent compared with bendamustine plus Rituxan, a current standard of care (HR=0.19; 95 percent CI 0.13-0.28; p<0.0001).

The most common side effects of Venclexta in combination with Rituxan include low white blood cell count, diarrhea, upper respiratory tract infection, cough, fatigue and nausea.

Today's FDA approval converts Venclexta's accelerated approval to a full approval. The FDA has also updated the indication for Venclexta as a single agent, which is now approved for the treatment of people with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy. Venclexta was previously granted accelerated approval in April 2016 as a single agent for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy.

The supplemental New Drug Application (sNDA) based on the MURANO data was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The FDA also previously granted Breakthrough Therapy Designation for Venclexta in combination with Rituxan for the treatment of relapsed or refractory CLL. Venclexta in combination with Rituxan is recommended in the National Comprehensive Cancer Network (NCCN) guidelines as a treatment option for previously treated CLL (Category 1, Preferred).

An application for a variation of the marketing authorization based on the MURANO data has also been submitted to and validated by the European Medicines Agency (EMA). Additional submissions of the MURANO data to health authorities around the world are ongoing.

https://www.gene.com/media/press-releases/14728/2018-06-08/genentech-announces-fda-approval-for-ven

FDA approves combination of Venclexta and Rituxan for lymphocytic leukemia treatment

Infant Omega-3 Supplementation Tied to Decreased Waist Size

In continuation of my update on Omega-3 fatty acids

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in infancy is associated with reduced insulin concentrations and insulin resistance in boys and reduced waist circumference in both sexes at age 5 years, according to a study published online June8 in Pediatrics.

Valene H.L. See, Ph.D., from the Royal Perth Hospital in Australia, and colleagues randomly assigned 420 infants to a daily supplement of n-3 LCPUFA or olive oil (control) from birth to 6 months. Growth, body composition, and cardiometabolic risk factors were evaluated at 5 years of age.

The researchers found that infants who received n-3 LCPUFA had a smaller waist circumference at 5 years (coefficient, 1.1 cm), which remained significant after adjusting for confounders (coefficient, 0.8 cm). Boys who received n-3 LCPUFA supplementation had a 21 percent reduction in insulin concentrations and a 22 percent reduction in insulin resistance versus the control group. At birth, 2.5 years, and 5 years, there were no other differences in growth and cardiometabolic risk factors between the groups.

"Longer-term follow-up of the cohort is warranted to determine whether these differences are maintained into adolescence," write the authors

Infant Omega-3 Supplementation Tied to Decreased Waist Size..

In continuation of my update on Omega-3 fatty acids

Omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation in infancy is associated with reduced insulin concentrations and insulin resistance in boys and reduced waist circumference in both sexes at age 5 years, according to a study published online June8 in Pediatrics.

Valene H.L. See, Ph.D., from the Royal Perth Hospital in Australia, and colleagues randomly assigned 420 infants to a daily supplement of n-3 LCPUFA or olive oil (control) from birth to 6 months. Growth, body composition, and cardiometabolic risk factors were evaluated at 5 years of age.

The researchers found that infants who received n-3 LCPUFA had a smaller waist circumference at 5 years (coefficient, 1.1 cm), which remained significant after adjusting for confounders (coefficient, 0.8 cm). Boys who received n-3 LCPUFA supplementation had a 21 percent reduction in insulin concentrations and a 22 percent reduction in insulin resistance versus the control group. At birth, 2.5 years, and 5 years, there were no other differences in growth and cardiometabolic risk factors between the groups.

"Longer-term follow-up of the cohort is warranted to determine whether these differences are maintained into adolescence," write the authors

Topical Rapamycin Effective for TSC-Related Facial Angiofibromas

In continuation of my  update on Rapamycin

Topical rapamycin seems effective for tuberous sclerosis complex (TSC)-related facial angiofibromas, according to a study published online May 23 in JAMA Dermatology.

Mary Kay Koenig, M.D., from The University of Texas Health Science Center at Houston, and colleagues examined the efficacy and safety of topical rapamycin for TSC-related facial angiofibromas in a study involving 179 patients. Participants were randomized in a 1:1:1 ratio to topical formulation containing 1 percent rapamycin, 0.1 percent rapamycin, or vehicle alone (59, 63, and 57 patients, respectively). The formulation was applied daily to designated areas at bedtime.

The researchers observed clinically meaningful and statistically significant improvement in facial angiofibromas for 1 and 0.1 percent rapamycin versus vehicle only, and for 1 versus 0.1 percent rapamycin; most of the improvement was seen in the first month. The Angiofibroma Grading Scale mean improvement at six months was 16.7, 11.0, and 2.1 points for 1 and 0.1 percent rapamycin and vehicle only, respectively (P < 0.001 for 1 and 0.1 percent versus vehicle only). End-of-treatment photos were rated better than baseline for 81.8, 65.5, and 25.5 percent of patients in the 1 and 0.1 percent rapamycin groups and the vehicle group, respectively (P < 0.001 for all three pairwise comparisons).

"Topical rapamycin appears effective and safe for treatment of TSC-related facial angiofibromas," the authors write. "In this trial, the preferred dose was 1 percent once daily."

Several authors disclosed financial ties to Novartis; one author disclosed ties to MedStudy. Several authors have a provisional patent pending

Ref : https://jamanetwork.com/journals/jamadermatology/article-abstract/2682034?resultClick=1

Eating raspberries improves function of cells lining blood vessels, research shows

In continuation of my update on Raspberry

New research led by Dr Ana Rodriguez-Mateos, School of Life Course Sciences, shows that eating red raspberries improves the function of the cells that line blood vessels.

Endothelial cells form the interior lining of our blood and lymphatic vessels. They act as a barrier between the blood or lymph and the surrounding body tissue as well as playing key roles in blood clotting and regulating blood pressure amongst other things. Sometimes these cells stop working efficiently (called endothelial dysfunction) which is thought to be a significant factor in the development of cardiovascular disease.

Dr Rodriguez-Mateos and her colleagues studied ten, healthy male volunteers aged 18-35 years. Participants were randomly given drinks containing no, 200g or 400g of raspberries. Researchers monitored chemicals in their blood and urine as well as their blood pressure and flow-mediated dilation (FMD) of the brachial artery: a measure of how the artery widens when blood flow increases.

The results showed a significant increase in FMD for participants that drank raspberry-containing drinks. The effect lasted for at least 24 hours and there was also a correlating increase in the levels of urolithin metabolites found in their blood. These are produced by bacteria in the gut as ellagitannins, a chemical found in raspberries, are digested. Researchers believe that ellagitannins could therefore be beneficial to vascular health.

If the change in FMD seen could be sustained for long enough, it would reduce a person's risk of developing cardiovascular disease by up to 15%. Further studies are needed to establish whether these results translate into long-term health benefits in the general population and whether red raspberries and other foods rich in ellagitannins (such as strawberries, pomegranate or nuts) should be included as part of a healthy diet to help prevent cardiovascular disease.

Speaking of the findings Dr Rodriguez-Mateos said:

'Although more studies are needed to confirm our findings, we are very excited about the potential role of raspberries and ellagitannins in cardiovascular disease prevention. Following up on this study, we are now investigating the long-term benefits of ellagitannins in a larger group of healthy individuals and we are also looking at how our gut microbiota may have an impact on their health benefits.

More : https://www.kcl.ac.uk/lsm/schools/life-course-sciences/news-events/newsrecords/2018/could-eating-raspberries-prevent-cardiovascular-disease.aspx

Alnylam announces new positive results from Phase 1/2 study of lumasiran in patients with PH1

Alnylam Pharmaceuticals, Inc., the leading RNAi therapeutics company, announced new positive results from its Phase 1/2 study with lumasiran, an investigational RNAi therapeutic targeting glycolate oxidase (GO) for the treatment of Primary Hyperoxaluria Type 1 (PH1). Results were presented at the OxalEurope, European Hyperoxaluria Consortium, taking place on June 8, 2018 in Naples, Italy.

Updated interim data were from Part B of the Phase 1/2 study and were as of the data cut-off date of March 29, 2018. Part B is a randomized (3:1 drug:placebo), single-blind, placebo-controlled evaluation of lumasiran in patients with PH1. Cohorts 1 and 2 received three monthly doses of lumasiran at 1 mg/kg or 3 mg/kg, respectively; Cohort 3 received two quarterly doses at 3 mg/kg. An additional eight patients received open-label lumasiran in expansions of each of the first two cohorts, totaling 20 patients enrolled. Patients randomized to the placebo group also received subsequent subcutaneous administration of lumasiran following administration of placebo. Patients had a mean age of 14.9 years (range: 6-43) and a mean estimated glomerular filtration rate (eGFR) of 77 mL/min/1.73m2 (range: 42-131).

Lumasiran demonstrated a mean maximal reduction in urinary oxalate of 64 percent in patients enrolled in Cohorts 1-3 (N=12). All lumasiran-treated patients experienced a lowering in urinary oxalate below 0.7 mmol/24 hrs/1.73m2, a threshold level associated with a reduced rate of progression to end-stage renal disease. On day 85, patients receiving lumasiran (N=9) maintained a mean reduction in urinary oxalate of 63 percent (range: 49-73 percent). Alnylam believes the potent and durable reductions in urinary oxalate support a once quarterly, subcutaneous dose regimen. Further, these results continue to support the hypothesis that GO inhibition has the potential to reduce and possibly normalize levels of hepatic oxalate production, thus potentially halting PH1 disease progression. Dosing in Part B of the Phase 1/2 study is ongoing and eligible patients are transitioning into an open-label extension (OLE) study. The Company expects to present additional data from all cohorts as well as from the OLE study in late 2018.

"We are pleased to present data that signal hope to patients with PH1, an ultra-rare, life-threatening disease, with a profound unmet need. Given the encouraging results, we believe that lumasiran has the potential to alleviate the pathologic overproduction of oxalate, the metabolite that causes the severe, systemic manifestations of PH1. Furthermore, we believe these results validate our approach of targeting GO, a key liver enzyme involved in the excessive oxalate output in patients with PH1," said Pritesh J. Gandhi, PharmD., Vice President and General Manager, Lumasiran program at Alnylam. "Based upon our recent discussions with the FDA, we are on track to advance this program into Phase 3 development at mid-year, with the goal of bringing lumasiran to patients around the world as rapidly as possible."

"PH1 is an ultra-orphan disease, with a generally pediatric onset and an immediate need for an effective intervention. Today, patients with advanced disease have no choice but to undergo intensive dialysis and, ultimately, a dual liver/kidney transplant, with no other approved treatment alternatives in place," said Prof. Bernd Hoppe, M.D., Head of the Division of Pediatric Nephrology, Department of Pediatrics, University of Bonn, Germany and an investigator in the lumasiran study. "The data presented on lumasiran provide evidence for oxalate reduction, highlighting the potential of this investigational medicine as an innovative approach for the treatment of patients with PH1."

Lumasiran was generally well tolerated in all patients in the Phase 1/2 study (N=20). Fifteen (75 percent) of patients treated with lumasiran experienced an adverse event (AE); the majority of AEs were mild or moderate in severity and unrelated to study drug. AEs occurring in three or more patients included abdominal pain, headache, nasopharyngitis, pyrexia, and vomiting. Two patients reported injection site reactions, both of which were mild and transient. Two patients reported severe AEs; one patient had pyelonephritis during placebo dosing and one patient had a kidney stone with renal colic after lumasiran dosing. One patient receiving placebo and three patients receiving lumasiran reported serious adverse events (SAEs); none were assessed as related to study drug. The placebo patient experienced kidney stones and pyelonephritis. The lumasiran patients with SAEs included one patient with kidney stones, one patient with fever and abdominal pain, and one patient with gastroenteritis. Lumasiran has not been associated with any clinically significant adverse laboratory findings, and there were no study discontinuations due to AEs through the data cut-off date.

Alnylam recently announced alignment with the U.S. Food and Drug Administration (FDA) on a pivotal study design for lumasiran, including a primary endpoint at six months based on reduction of urinary oxalate, and a study size of approximately 25 patients with PH1. The Company has guided its intention to initiate the Phase 3 trial in mid-2018. Lumasiran has received Breakthrough Therapy Designation from the FDA and Priority Medicines (PRIME) designation from the European Medicines Agency (EMA).

Ref : http://investors.alnylam.com/news-releases/news-release-details/alnylam-reports-updated-positive-results-phase-12-study

Alnylam announces new positive results from Phase 1/2 study of lumasiran in patients with PH1