Sun Pharma Announces FDA Approval of Cequa (cyclosporine) Ophthalmic Solution to Treat Dry Eye Disease

Sun Pharmaceutical Industries Ltd, announced that Sun Pharma has received approval for Cequa (cyclosporine ophthalmic solution) 0.09%, from the U.S. Food and Drug Administration (FDA). Cequa is indicated to increase tear production in patients with keratoconjunctivitis sicca (dry eye).

                   

Cequa provides the highest FDA-approved concentration of cyclosporine A (CsA) and is the first and only approved CsA product that incorporates a nanomicellar technology. The innovative nanomicellar formulation allows the CsA molecule to overcome solubility challenges, penetrate the eye’s aqueous layer and prevents the release of the active lipophilic molecule prior to penetration. In the Phase 3 confirmatory trial on Cequa, after 12 weeks of treatment, as compared to vehicle, Cequa showed statistically significant improvement in the primary endpoint, Schirmer’s score (a measurement of tear production) (p<0.01). Improvements in secondary endpoints (i.e. ocular staining assessments) were seen as early as 1 month after initiating treatment. Cequa is dosed twice daily and will be available as a single-use vial.

The nanomicellar formulation technology uses micelles, which are gelatinous aggregates of amphipathic (both hydrophobic and hydrophilic) molecules formed at a well-defined concentration. The small size of the nanomicelles facilitates entry into corneal and conjunctival cells, enabling delivery of high concentrations of CsA.

“Dry Eye Disease represents an area of high unmet medical need, with a significant number of patients who are currently untreated,” said Abhay Gandhi, CEO, North America, Sun Pharma. “The U.S. FDA approval of Cequa represents a long-awaited dry eye treatment option and is an important milestone in the development of Sun’s Ophthalmics business. Cequa, with its novel nanomicellar formulation for a proven dry eye medication, delivers a lipophilic molecule in a clear solution form.”

Additionally, Jodi Luchs, MD, the principal investigator behind the Cequa confirmatory Phase 3 trial, noted: “Dry eye is a complex disease that lacks a ‘one-size-fits-all’ approach. As a clinician treating a high volume of dry eye patients, it’s important to have multiple treatment modalities available at my disposal. Given its strong clinical trial performance, the approval of Cequa is welcomed news, and I look forward to offering my patients this compelling new option.”

Cequa (cyclosporine ophthalmic solution) 0.09%, for topical ophthalmic use will be commercialized in the U.S. by Sun Ophthalmics, the branded ophthalmics division of Sun Pharma’s wholly owned subsidiary.

Sun Pharma Announces FDA Approval of Cequa (cyclosporine) Ophthalmic Solution to Treat Dry Eye Disease

Four cups of coffee a day shown to protect heart muscle

In continuation of my update on coffee

A new study has shown that drinking four cups of coffee a day can protect against heart muscle damage through the effect of caffeine on a protein called p27

Caffeine intake has been associated with a lower risk of several chronic metabolic diseases such as cardiovascular disease (stroke and ischemic heart disease), and type II diabetes.

The current study, which was carried out at Heinrich-Heine-University and the IUF-Leibniz Research Institute for Environmental Medicine in Duesseldorf, Germany, shows that caffeine, at a concentration equivalent to that in four cups of coffee, works to enhance the mitochondrial entry of a protein called p27.

P27 is protein that promotes effective mitochondrial function. It protects the cells of the heart and blood vessels against damage. The study was recently published in the open access journal PLOS Biology.

Prior research by the same scientists revealed that caffeine improves the function of endothelial cells that line the cardiovascular system. This was seen to occur at normal, safe doses and was related to mitochondria.

Following the study, the scientists focused on the p27 protein, known better as a cell cycle inhibitor, and found that it was present within the mitochondria of all major cell-types in the heart.

The p27 protein prevents cell death in cardiac muscle cells, encourages endothelial cells to migrate, and promotes the maturation of fibroblasts into contractile cells. These processes are vital components of cardiac muscle repair following a heart attack.

Caffeine promotes this repair by facilitating the first step, namely, the entry of p27 protein into the mitochondria, at physiologic levels. This protective effect against heart damage is present in elderly, obese and prediabetic mice.

Our results indicate a new mode of action for caffeine, one that promotes protection and repair of heart muscle through the action of mitochondrial p27. These results should lead to better strategies for protecting heart muscle from damage, including consideration of coffee consumption or caffeine as an additional dietary factor in the elderly population.”

Dr. Judith Haendeler, Heinrich-Heine-University

Ref : https://www.eurekalert.org/pub_releases/2018-06/p-cff061418.php

FDA approves new marijuana-based drug to treat rare and severe forms of epilepsy

In continuation of my update on Cannabidiol

The U.S. Food and Drug Administration today approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, in patients two years of age and older. This is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It is also the first FDA approval of a drug for the treatment of patients with Dravet syndrome.

CBD is a chemical component of the Cannabis sativa plant, more commonly known as marijuana. However, CBD does not cause intoxication or euphoria (the "high") that comes from tetrahydrocannabinol (THC).

It is THC (and not CBD) that is the primary psychoactive component of marijuana.

"This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies. And, the FDA is committed to this kind of careful scientific research and drug development," said FDA Commissioner Scott Gottlieb, M.D. "Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA's drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug's uniform strength and consistent delivery that support appropriate dosing needed for treating patients with these complex and serious epilepsy syndromes. We'll continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products. But, at the same time, we are prepared to take action when we see the illegal marketing of CBD-containing products with serious, unproven medical claims. Marketing unapproved products, with uncertain dosages and formulations can keep patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases."

Dravet syndrome is a rare genetic condition that appears during the first year of life with frequent fever-related seizures (febrile seizures). Later, other types of seizures typically arise, including myoclonic seizures (involuntary muscle spasms). Additionally, status epilepticus, a potentially life-threatening state of continuous seizure activity requiring emergency medical care, may occur. Children with Dravet syndrome typically experience poor development of language and motor skills, hyperactivity and difficulty relating to others.

Lennox-Gastaut syndrome begins in childhood. It is characterized by multiple types of seizures. People with Lennox-Gastaut syndrome begin having frequent seizures in early childhood, usually between ages 3 and 5. More than three-quarters of affected individuals have tonic seizures, which cause the muscles to contract uncontrollably. Almost all children with Lennox-Gastaut syndrome develop learning problems and intellectual disability. Many also have delayed development of motor skills such as sitting and crawling. Most people with Lennox-Gastaut syndrome require help with usual activities of daily living.

"The difficult-to-control seizures that patients with Dravet syndrome and Lennox-Gastaut syndrome experience have a profound impact on these patients' quality of life," said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research. "In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition."

Epidiolex's effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials involving 516 patients with either Lennox-Gastaut syndrome or Dravet syndrome. Epidiolex, taken along with other medications, was shown to be effective in reducing the frequency of seizures when compared with placebo.

The most common side effects that occurred in Epidiolex-treated patients in the clinical trials were: sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor quality sleep; and infections.

Epidiolex must be dispensed with a patient Medication Guide that describes important information about the drug's uses and risks. As is true for all drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks. Epidiolex also caused liver injury, generally mild, but raising the possibility of rare, but more severe injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and/or dark urine.

Under the Controlled Substances Act (CSA), CBD is currently a Schedule I substance because it is a chemical component of the cannabis plant. In support of this application, the company conducted nonclinical and clinical studies to assess the abuse potential of CBD.

The FDA prepares and transmits, through the U.S. Department of Health and Human Services, a medical and scientific analysis of substances subject to scheduling, like CBD, and provides recommendations to the Drug Enforcement Administration (DEA) regarding controls under the CSA. DEA is required to make a scheduling determination.

The FDA granted Priority Review designation for this application. Fast-Track designation was granted for Dravet syndrome. Orphan Drug designation was granted for both the Dravet syndrome and Lennox-Gastaut syndrome indications.

Ref : https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611046.htm

Fluconazole Use Doesn't Up Risk of Stillbirth, Neonatal Death

In continuation of my update on Fluconazole

Fluconazole use in pregnancy seems not to be associated with significantly increased risks of stillbirth or neonatal death, according to a research letter published in the June 12 issue of the Journal of the American Medical Association.

Björn Pasternak, M.D., Ph.D., from the Karolinska Institutet in Stockholm, and colleagues examined whether fluconazole use during pregnancy is associated with stillbirth and neonatal death. The authors used nationwide register data to identify all pregnancies with singleton live births and stillbirths in Sweden and Norway. A total of 10,669 exposed and 106,690 unexposed pregnancies from a cohort of 1,485,316 pregnancies were included in the matched analysis of stillbirth, and 10,640 exposed and 106,387 unexposed pregnancies were included in the matched analysis of neonatal death.

The researchers found that there were 2.7 and 3.6 stillbirths per 1,000 exposed and unexposed pregnancies, respectively (hazard ratio, 0.76; 95 percent confidence interval, 0.52 to 1.1) and 1.2 and 1.7 neonatal deaths per 1,000 exposed and unexposed pregnancies, respectively (risk ratio, 0.73; 95 percent confidence interval, 0.42 to 1.29). Similar results were seen for doses of 300 mg or less and more than 300 mg.

"Although the data on fluconazole use in pregnancy suggest no increased risk of stillbirth, additional studies should be conducted and the collective body of data scrutinized by drug authorities before recommendations to guide clinical decision making are made, and weighed against the benefits of therapy," the authors write.

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#