Pfizer gets OK for Xeljanz for ulcerative colitis in Europe

Pfizer has received approval from the European Commission (EC) to market Xeljanz (tofacitinib citrate) for the treatment of adults suffering from severely active ulcerative colitis (UC).

The indication covers use of 10mg twice-daily (BID) for at least eight weeks, followed by 5mg or 10mg BID of the drug in patients with inadequate response, lost response or intolerance to current standard therapy or a biologic agent.

Xeljanz is an inhibitor of Janus kinase (JAK), and is said to be the first such oral drug approved for this patient population.

The EC clearance is based on findings from three pivotal Phase III studies under the Oral Clinical Trials for Tofacitinib in Ulcerative colitis (OCTAVE) global clinical development programme, and the ongoing OCTAVE Open long-term extension study.

Pfizer Inflammation and Immunology regional president Angela Lukin said: Ulcerative colitis is a chronic disease that can develop at any age, be difficult to manage and affect multiple aspects of daily life.

The EC approval of Xeljanz provides an additional treatment option that can help improve the care of adults in Europe living with this debilitating inflammatory bowel disease.

Previously, the medicine was approved by the EC to treat active psoriatic arthritis (PsA) in patients who have had an inadequate response or intolerance to a previous disease-modifying antirheumatic drug (DMARD) therapy.

Xeljanz is also indicated in combination with methotrexate (MTX), for treating moderate to severe active rheumatoid arthritis (RA) in adults responding inadequately or intolerant to one or more DMARDs.

It additionally gained approval as monotherapy for patients intolerant to MTX or in cases when treatment with MTX is considered inappropriate.

Currently, Xeljanz is available for moderate to severe RA in more than 80 countries, and for moderately to severely active UC in the US, Japan, Peru and Russia.

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Vitamin D: Recent research uncovers new benefits

As much of the world experiences a record-breaking heat wave, this Spotlight turns its attention to vitamin D, the so-called sunshine vitamin. Here, we inspect the latest research.

Vitamin D is a hot topic currently, with a raft of studies proclaiming its benefits for a variety of serious conditions.

Conversely, other recent studies have been more cautious, questioning its perceived usefulness for treating some illnesses.

Vitamin D is a nutrient that is synthesized in our skin when it is exposed to sunlight, and it is also present in some foods.

Sunlight is the best source of vitamin D, but in the winter months, the National Institutes of Health (NIH) recommend topping up vitamin D levels by eating vitamin D-containing foods each day. These include oily fish, fortified milk, beef liver, egg yolks, mushrooms, and fortified breakfast cereals.

What does vitamin D do?

Scientists know that vitamin D is essential for many aspects of maintaining good health and that deficiency is linked with problems for both physical and mental health.

Perhaps most notably, vitamin D helps to regulate the levels of calcium in our bodies, strengthening our bones and preventing bone-weakening conditions, such as osteoporosis.

Increasingly though, studies are also suggesting that vitamin D might have protective benefits against heart failure, diabetes, cancer, respiratory tract infections, autoimmune disease, and even hair loss.

A surprisingly large number of people have insufficient levels of vitamin D. For instance, according to one study, more than 40 percent of adults in the United States are deficient. Because of its prevalence, it is important to determine what the public health implications of this epidemic might be.

Symptoms of vitamin D deficiency can vary between individuals, but they typically include pain in the joints, muscles, or bones; fatigue; breathing problems; and low mood or seasonal affective disorder (SAD).

Below, we run through a number of intriguing recent studies that investigate associations between vitamin D and an assortment of illnesses.

Vitamin D and heart failure

Several studies have suggested that vitamin D could offer protective benefits against cardiovascular illness, but scientists have yet to pinpoint what mechanisms are driving this association.

Recently, though, Medical News Today reported on a study that used a mouse model to investigate how a type of vitamin D, called 1,25-dihydroxyvitamin D3, affects heart cells. In particular, the researchers looked at the cells responsible for developing scar tissue following a heart attack, called cardiac colony-forming unit fibroblasts (cCFU-Fs).

cCFU-Fs are an important area of study because, when heart tissue is scarred, the heart has a harder time pumping blood, which can lead to heart failure.

The researchers behind the study found that vitamin D inhibited the action of cCFU-Fs, which prevented scar tissue from building around the hearts of the mice in the study, potentially preventing blockages in the cardiovascular system.

“With further study,” wrote the authors, “vitamin D could prove to be an exciting, low-cost addition to current treatments, and we hope to progress these findings into clinical trials for humans.”

Vitamin D and cancer

Breast cancer and bowel cancer have both been linked with cases of vitamin D deficiency in recent studies. One of these analyzed data from two randomized clinical trials and a prospective cohort study.

The researchers found that high levels of vitamin D were inversely associated with risk of breast cancer among women who were cancer-free at baseline.

According to the study results, the higher the levels of vitamin D, the lower the risk of breast cancer.

This relationship remained significant even after the results were adjusted for confounding factors, such as age, body mass index (BMI), intake of calcium supplements, and smoking habits.

Although a link between vitamin D deficiency and colorectal cancer has previously been reported, not all studies have been able to replicate these findings. A new, large-scale study attempted to settle this by drawing on data from three continents, including 5,700 colorectal cancer cases and 7,100 controls.

The researchers calculated that people whose levels of vitamin D fall below those specified in the current guidelines have a 31 percent increased risk of developing bowel cancer. By contrast, those with vitamin D levels above the current recommended levels were 22 percent less likely to develop this cancer.

Vitamin D and belly fat

Another recent study examined a previously observed link between obesity and lower levels of vitamin D, focusing in particular on how different types of body fat might interact with vitamin D.

The study authors reported that having excess belly fat was linked with lower levels of vitamin D:

“[T]he strong relationship between increasing amounts of abdominal fat and lower levels of vitamin D suggests that individuals with larger waistlines are at a greater risk of developing deficiency and should consider having their vitamin D levels checked.”

However, the study was not able to prove whether a deficiency in vitamin D causes fat to be stored around the belly, or if having belly fat somehow contributes to a deficiency in vitamin D. The researchers say that future studies will attempt to determine cause and effect in this relationship.

Vitamin D and Alzheimer’s disease

A systematic review from researchers in Australia recently attempted to settle the debate surrounding vitamin D’s ability to protect against Alzheimer’s. The systematic review analyzed more than 70 studies looking at the association.

They concluded that there was no significant association between vitamin D deficiency and risk of Alzheimer’s.

Intriguingly, the authors did suggest that — based on their systematic review — there may be an association between exposure to the sun’s ultraviolet rays and protection against multiple sclerosis, Parkinson’s disease, and Alzheimer’s, but that this may be independent of vitamin D production.

The authors said that further studies would be needed to confirm these links and identify the mechanism responsible for such associations.

Vitamin D and chronic pain

Over the years, some scientists have theorized that low levels of vitamin D might cause or worsen chronic pain.

So, in 2015, a group of scientists set out to collate existing evidence to examine the relationship.

The resulting Cochrane review, updated in 2015, explains that:

“Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the etiology of chronic painful conditions.” The team scrutinized the findings from a number of studies.

Following the analysis, they concluded that the available scientific evidence is not strong enough to support a connection between vitamin D deficiency and chronic pain.

The authors write, “Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.”

So, as ever, more work will be needed to finally close the lid on this interaction.

We hope this article has enhanced your understanding of the latest scientific thinking around this fascinating chemical. Please remember, however, that over-exposure to sunlight — especially the hot, midday sun — can result in skin damage and increase risk of skin cancer.

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Existing drug may prevent Alzheimer’s

Emerging evidence suggests that a “potent” drug could prevent the development of Alzheimer’s disease — but only if a person takes the medication long before symptoms of this condition make an appearance.

Alzheimer’s disease is the most common form of dementia; according to the Centers for Disease Control and Prevention (CDC), an estimated 5.7 million adults in the United States live with this condition.

Unfortunately, there is no cure for Alzheimer’s, and following disease onset, symptoms tend to worsen progressively.

Then, the question, “Can specialists prevent the disease in people deemed at increased risk?” arises.

The authors of a new study, from the University of Virginia in Charlottesville, suggest that one drug called memantine — which is currently used to manage Alzheimer’s symptoms — may actually help prevent the disease. This, however, might only happen if a person takes the drug before symptoms set in.

“Based on what we’ve learned so far, it is my opinion that we will never be able to cure Alzheimer’s disease by treating patients once they become symptomatic,” says Prof. George Bloom, of the University of Virginia, who oversaw the study.

“The best hope for conquering this disease is to first recognize patients who are at risk, and begin treating them prophylactically with new drugs and perhaps lifestyle adjustments that would reduce the rate at which the silent phase of the disease progresses,” he says, adding, “Ideally, we would prevent it from starting in the first place.”

The journal Alzheimer’s & Dementia has now published the team’s findings.

The cell cycle re-entry process

The researchers explain that Alzheimer’s disease actually begins long before symptoms start to show — perhaps even a decade or longer in advance.

One of the condition’s characteristics is that, once affected by the disease, brain cells attempt to divide — possibly in order to balance out the death of other neurons — only to die, anyway.

In any case, the further division of fully formed brain cells is unusual and does not happen in a healthy brain. The affected neurons’ attempt at division is called the “cell cycle re-entry process.”

“It’s been estimated that as much as 90 percent of neuron death that occurs in the Alzheimer’s brain follows this cell cycle re-entry process, which is an abnormal attempt to divide,” explains Prof. Bloom.

“By the end of the course of the disease, the patient will have lost about 30 percent of the neurons in the frontal lobes of the brain,” he estimates.

Study co-author Erin Kodis — Prof. Bloom’s former doctoral student — formed her own hypothesis about what triggers this mechanism.

Excess calcium, she believes, enters neurons through special receptors called NMDA receptors on the cells’ surface. This drives brain cells to start dividing.

Following a series of laboratory experiments, Kodis confirmed that her hypothesis was correct. This mechanism is set in motion before the formation of amyloid plaques, which are characteristic of Alzheimer’s disease, in the brain.

Eventually, however, molecules of an amino acid called beta amyloid stick together to form toxic amyloid plaques.

Memantine may have ‘potent properties’

Kodis saw that when neurons encounter beta amyloid molecules in the early stages that precede plaque buildup, NMDA receptors open to receive the excess calcium that ultimately leads to their destruction.

But then the researcher made another discovery: the drug memantine prevented cell cycle re-entry by closing the NMDA receptors on the surface of neurons.

“The experiments suggest that memantine might have potent disease-modifying properties if it could be administered to patients long before they have become symptomatic and diagnosed with Alzheimer’s disease.”

Prof. George Bloom

“Perhaps this could prevent the disease or slow its progression long enough that the average age of symptom onset could be significantly later, if it happens at all,” Prof. Bloom adds.

These findings are particularly promising; memantine has few known side effects, and those that have been reported are rare and do not have a major impact on an individual’s well-being.

Prof. Bloom believes that, in the future, a useful preventive approach might be to screen people for telling signs that they are exposed to Alzheimer’s as early as possible.

Specialists could then prescribe memantine to those at an increased risk of the disease, he says. People may have to take the drug throughout their lives to keep Alzheimer’s at bay — or at least in check.

“I don’t want to raise false hopes,” says Prof. Bloom. However, he continues, “[I]f this idea of using memantine as a prophylactic pans out, it will be because we now understand that calcium is one of the agents that gets the disease started, and we may be able to stop or slow the process if done very early.”

Currently, Prof. Bloom and colleagues are planning a clinical trial to test the preventive strategy that they outlined in the study.

https://bit.ly/2vg0AjC

How to Keep Foodborne Illness at Bay

When you’re having a barbecue or picnic, be sure you don’t invite foodborne illnesses caused by salmonella bacteria.

Each year in the United States, salmonella causes about 1.2 million illnesses and 23,000 hospitalizations, according to the U.S. Centers for Disease Control and Prevention.

Salmonella contamination can occur in many foods, including melons, cucumbers, chicken, eggs, raw tuna and sprouts, the Association for Professionals in Infection Control and Epidemiology (APIC) warns.

Salmonella-caused illness (salmonellosis) is most common during the summer months because of warm temperatures, delayed refrigeration and the types of foods people enjoy in the summer.

APIC suggests a number of ways to reduce the risk of salmonellosis:

• Prevent cross-contamination by always washing your hands after handling raw meat.
•  Keep kitchen surfaces and utensils clean.
• Wash fruits and vegetables before you cut or peel them. Use a scrub brush to reduce contaminants on the rough skin of foods like cantaloupe.
• Use separate cutting boards and knives for uncooked meats and uncooked produce.
• Keep hot foods hot and cold foods cold.
• Cook food to recommended internal temperatures: whole meats 145 degrees Fahrenheit (F), ground meats 160 degrees F, and poultry 165 degrees F.
• Refrigerate perishable food (including melon) within two hours. Throw away food that sits out longer than two hours.

Call a health care provider if you think you or someone else has salmonellosis. The symptoms include: diarrhea and a fever over 101.5 degrees F; dehydration; bloody stools; diarrhea that lasts three or more days; prolonged vomiting without being able to keep liquids down.

More information

The U.S. Centers for Disease Control and Prevention has more on salmonella.

SOURCE: Association for Professionals in Infection Control and Epidemiology, news release, July 18, 2018

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Roche, Johnson & Johnson pulled into DOJ probe of alleged terrorist bribes

Days after AstraZeneca disclosed that its under Justice Department scrutiny for allegedly funding Iraqi terrorism, Johnson & Johnson and Roche also revealed similar inquiries from the agency.

Federal prosecutors got in touch with the companies after a veterans` lawsuit accused them of bribing Iraqi health officials. J&J disclosed that lawsuit in a securities filing last year, and this week stated that the feds had started their own investigation. Also, the company has received an inquiry from the United States Department of Justiceregarding the matters set out in the complaint, J&J said in its second-quarter SEC filing.

Separately, a Roche spokeswoman confirmed to FiercePharma that the Swiss drugmaker has received an inquiry from and is cooperating with the Department of Justice on this matter.

The initial lawsuit was brought last October by more than 100 U.S. veterans and their families. They allege that to win favorable pharmaceutical and medical device contracts in Iraq, J&J, Roche, AstraZeneca, GE Healthcare and Pfizer made bribes to the terrorists who openly controlled the Iraqi Ministry of Health.

Pfizer didnt immediately respond to a request for comment and hasnt filed its quarterly document to the Securities and Exchange Commission. But at the time the lawsuit was first filed, a Pfizer spokesperson said the company categorically denies any wrongdoing.

General Electriccurrently in the process of separating GE Healthcare into a standalone company so that it can focus on power, energy and aviation businessesdidnt mention any similar DOJ probe in its second-quarter regulatory filing.

Johnson & Johnson and GE didnt reply to FiercePharma inquiries by publication time.

An AZ spokesperson on Tuesday told FiercePharma the company has a robust and dynamic compliance program, and we refuse to tolerate bribery or any other form of corruption.

The veterans` lawsuitbased on evidence drawn from 12 confidential witnesses, as well as public and private documentsclaims that the briberies began under Saddam Husseins regime, whose Ministry of Health relied on a corrupt procurement process that opened the door to such illicit payments.

According to the complaint, the pattern of payments continued after Saddams government collapsed and the ministry passed under the control of a Shiite terrorist group. One alleged payment scheme, according to the plaintiffs, involved providing ministry officials with drugs and medical equipment free of charge so they could resell them on the black market.

https://bit.ly/2viqfrY

Takeda, Partner Set Joint Fund to Promote Drug Discovery in Japan

Takeda Pharmaceutical Company Limited (TSE: 4502) (“Takeda”) and Japan-based Alternative Asset Management Firm, Whiz Partners, Inc. (“Whiz”) today announced they have entered into an agreement to create a joint investment fund, aimed at promoting a drug discovery ecosystem in Japan. This investment fund will be called “Drug Discovery Gateway Investment Limited Partnership” (“DDG Fund”), and will launch in November 2018.

Under the terms of the agreement, Whiz will establish the DDG Fund and assume the responsibilities of the general partner. Takeda will invest Axcelead Drug Discovery Partners (“Axcelead”), a wholly owned subsidiary of Takeda and a drug discovery platform company, in kind into the DDG Fund, in return for Limited Partner Shares. The DDG Fund will approach domestic and global financial investors and the biopharma/pharmaceutical industry to join the fund as limited partners. In this way, these strategic investments in academia and venture startups will help to realize innovative medicines and therapies supported by Axcelead.

Axcelead started its drug discovery platform business in July 2017, after being transferred from Takeda’s drug discovery research division, as the first integrated drug discovery solution provider in the Japanese pharmaceutical industry. Axcelead is equipped with all functions related to non-clinical drug discovery research and personnel with extensive skills, knowledge and experience in all fields. As such, Axcelead provides diverse and innovative healthcare institutions involved in drug discovery/development in Japan and other countries, with a one-stop solution service tailored to each of their needs. Furthermore, these services are offered in a wide spectrum of therapeutic areas, ranging from exploratory research and the optimization of candidate compounds to the process of bridging such initiatives to clinical development.

As a company independent from Takeda after the latter’s in-kind investment into the DDG Fund, Axcelead will provide a wide assortment of drug discovery services for not only Takeda but also other pharmaceutical companies and venture startups. By integrating strategic investments in academia and venture startups with experience and platform of drug discovery in Axcelead, the DDG Fund will lead the drug discovery ecosystem in Japan with the aim of achieving success as a fund.

“As exemplified by the launch of Shonan Health Innovation Park earlier this year, Takeda and its partners are committed to working with industry experts to collaborate and translate cutting-edge science into impactful health solutions for the benefit of patients in Japan and across the world,” said Dr. Toshio Fujimoto, General Manager of Shonan iPark. “We are pleased that the mission of the DDG fund aligns with this vision and that the drug discovery expertise Axcelead provides to partners in Shonan Health Innovation Park will now be accessible to a broad range of companies within the DDG investment fund, as well as potential new partners worldwide.”

“I believe that Japan has at last had an environment ready for establishing a drug discovery ecosystem, due to factors such as that bio-technology ventures have accumulated experiences, that capable human resources at pharmaceutical companies have become more liquid, that excellent seeds of drug discovery have grown even more promising, and that pharmaceutical companies with ample surplus funds are seeking to find effective investment opportunities for their sustainable growth,” said Tomoyuki Fujisawa, Chief Fund Manager of Whiz. “Establishment of the DDG Fund, which will mainly invest in Axcelead, with Takeda enables us to bring innovation to drug discovery in Japan.”

https://bit.ly/2O6pLMo

Insulin resistance under-diagnosed in non-diabetics with Parkinson’s disease

Almost two-thirds of non-diabetic patients with Parkinson’s disease (PD) may be insulin resistant, despite having normal blood sugar, report scientists in the Journal of Parkinson’s Disease. Their findings suggest that insulin resistance in PD is a common and largely undetected problem, especially in patients who are overweight.

Reduced glucose tolerance has long been recognized as a potential risk factor for PD, and there is increasing scrutiny of insulin resistance as a pathologic driver of neurodegeneration. The key link between the two conditions appears to be insulin resistance, a potentially reversible condition that not only predisposes individuals to type 2 diabetes (DM2) but is also associated with neurodegeneration. However, the prevalence of insulin resistance in PD is unknown.

“There is growing interest in the study of this relationship and the use of diabetes medications in the treatment of PD. However, there is little information regarding the prevalence of insulin resistance in PD,” explained lead investigator Michele Tagliati, MD, from the Department of Neurology, Cedar-Sinai Medical Center, Los Angeles, CA, USA. “This study is the first to address this question in a large population of non-diabetic patients.”

Investigators tested 154 non-diabetic PD patients for fasting blood sugar and insulin to assess the prevalence of insulin resistance and to correlate insulin resistance with other metabolic indicators, motor and non-motor symptoms of PD, and quality of life. Based a widely used formula, known as the HOMA index, they determined how many of these patients had a reduced response to their own insulin. Among other measurements, their weight and height were recorded and their movement and cognitive performance were measured.

Results showed that nearly two-thirds of patients (58.4%) had undiagnosed insulin resistance, despite normal fasting glucose and, in many cases, normal hemoglobin A1c (HbA1c), a test that is regularly performed for type 1 and type 2 diabetes. Their data confirmed previous studies that insulin resistance is more than double in obese compared with lean individuals, but the investigators also found a substantially higher percentage (41%) of lean PD patients with insulin resistance. They found no correlation between insulin resistance and cognitive decline.

The potential impact of this study is two-fold. Weight gain and obesity is a major public health challenge and insulin resistance appears linked to body weight. These findings could lead to increased screening of PD patients to detect and correct this condition.

The second and more specific impact is that identifying patients with insulin resistance could allow for personalized medicine, whereby PD patients with insulin resistance may be treated with medications targeted to reverse the condition. Research on the use of diabetic medications for PD, such as GLP-1 agonists like exenatide and liraglutide, is ongoing.

“Now that, for the first time, we understand how common insulin resistance is in non-diabetic patients with PD, we can begin to address this public health challenge,” commented Dr. Tagliati. “This increases the importance of finding new treatments and lifestyle interventions that can address this metabolic dysfunction with multiple implications, from diabetes to neurodegenerative disorders like PD and Alzheimer’s disease.”

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Story Source:

Materials provided by IOS Press. Note: Content may be edited for style and length.

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Journal Reference:

1. Elliot Hogg, Kishore Athreya, Christina Basile, Echo E. Tan, Jan Kaminski, Michele Tagliati. High Prevalence of Undiagnosed Insulin Resistance in Non-Diabetic Subjects with Parkinson’s Disease. Journal of Parkinson’s Disease, 2018; 8 (2): 259 DOI: 10.3233/JPD-181305

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