New FDA approved weight loss drug sees unprecedented demand

 A new prescription medication is dominating a weight loss market crowded with pills, powders, cleanses, juices, and more. In June of 2021, the FDA approved Wegovy (semaglutide), a weekly injectible.

According to the federal agency, it's "the first approved drug for chronic weight management in adults with general obesity or overweight since 2014."

"I think we started filling prescriptions for Wegovy in July of last year," said pharmacist Jon Phillips with Sage Specialty Pharmacy in Shorewood. "It's been very busy."

Phillips has about 50 to 60 patients currently taking the new weight loss medication. He said patients start with lower doses and work their way up.

"That's to help reduce the nausea side effect that can occur with this," said Phillips. "We've had lots of patients that in the first five to six months have lost 20 to 30 pounds easily."

"What we've seen in the clinical trials is that people who have been on Wegovy for a year have lost up to thirty percent of their body weight, which is huge. That's a big deal."

Phillips says the prescription is a game-changer and it's needed. The obesity epidemic is showing no signs of slowing down. The latest CDC data says more than 70 percent of American adults are overweight.

"It works on a certain receptor and it acts to reduce your hunger. It slows the speed of emptying in the stomach, which makes you feel fuller for a longer period of time and you seem to feel fuller faster," he explained.

Doctor Tammy Kindel is the Director of Adult and Adolescent Bariatric Surgery Program at Froedtert & MCW health network.

"We as clinicians are desperate for good, safe options," Dr. Kindel said.

She stresses the medication is not just a quick fix to losing weight.

"It takes time and takes daily effort, and our patients taking it know that. It's a comprehensive approach with diet, exercise, and even sometimes adding in surgery," said Kindel.

"The recommendations are around 500 kilocalories per day reduction in daily intake and then with increased activity,'" she said.

However, the cost for many patients is a concern.

"Cost and access are our biggest concerns right now. Effectiveness and safety profile looks much better, but it's hard to get this as a treatment for patients because it's so cost prohibitive," said Dr. Kindel.

No matter the dose, Wegovy's wholesale price is about $1,300 per month.

Phillips said some of his Medicaid patients have received full prescription coverage with prior authorization. Also, he said his pharmacy has had success in helping patients with private insurance navigate better coverage. He feels this new prescription doesn't just benefit the patient, but the insurer.

"They're not going to be paying as much for hypertension drugs. They're not going to be paying as much for people getting strokes. All of those kinds of things that happen because of being overweight," said Phillips.

Like with any medication, not everyone is a fan. Online people have complained of no weight loss, bad nausea, and hair loss.

That's certainly not impacting the drug's popularity.

Wegovy's drug manufacturer said its unprecedented product demand caused supply shortages and that until it can meet demand it's asking healthcare providers to not start new patients on the medication.

"There are some options out there. There's another drug called Saxenda which is used for the same thing, but it's a daily injection," Phillips said.

Earlier this month, the FDA approved a medication called Mounjaro. While right now it's only approved to treat patients with type 2 diabetes, that's how Wegovy started.

https://www.tmj4.com/news/local-news/new-fda-approved-weight-loss-drug-sees-unprecedented-demand-its-been-very-busy

Pathway to Prevent COVID Infection Discovered

 The Catholic University of Louvain (UCLouvain) in Belgium announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What's more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.

UCLouvain emphasized that this discovery, which was published in the scientific journal Nature Communications on May 10, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.

For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids (SAs), a kind of sugar residue present on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.

It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.

The researchers have now revealed a variant of these sugars that interacts more strongly with the S protein than other sugars do.

In other words, the university explained, they found the set of keys that allows the virus to open the cell door. So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein's points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell's entry door.

Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.

The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop an antiviral therapy administered by aerosol in the case of infection or at-risk contact.

This discovery is also of interest for the future, to counter other viruses with similar attachment factors.

This article was translated from MediQuality.

https://www.medscape.com/viewarticle/974617

Tin in Permanent Contraception Implants Causes Toxicity

 Essure implants arrived on the market in 2002 as permanent contraception for women older than age 45 years with children. They were recalled in 2017. Presented as an alternative to laparoscopic tubal ligation, this medical device resulted in rare side effects affecting thousands of women, most notably the nervous system, cardiovascular system, endocrine system, and musculoskeletal system.

Implant Analysis Protocol

A team from Lyon studied the wear debris from these medical devices and their possible toxic health effects. They discovered that tin could be the cause of the implant's toxicity. "My research focuses on a variety of medical devices, mostly joint replacements, and more specifically, hip replacements. I look at how these materials behave in humans and how the wear debris affects the body," explained Ana Maria Trunfio-Sfarghiu, bioengineering expert and research associate with the French National Center for Scientific Research at the Lyon National Institute of Applied Sciences' Contact and Structure Mechanics Laboratory.

"The problems with Essure implants started with a woman who had been using one for about 10 years and was experiencing side effects such as trouble concentrating and focusing, significant vaginal bleeding, extreme tiredness, hair loss, etc. She had the implant removed, and we retrieved it from her gynecologist and analyzed it alongside other implants," said Trunfio-Sfarghiu.

"Together with the hospital, we set up an implant analysis protocol. We visited hospital teams to demonstrate how to prepare the biopsies, embedded in paraffin blocks, before sending them to us for analysis. We gave the same specimen preparation instructions for all subjects," Trunfio-Sfarghiu explained.

After a year of clinical analysis, the Journal of Trace Elements in Medicine and Biology published an article about 18 cases.

Implant Weld Corrosion

The Essure implant measures a few centimeters long and resembles a small spring. Once released inside the fallopian tube, its goal is to create inflammation and block the tube. It triggers fibrosis, which prevents the sperm from reaching the egg. Premarketing tests had shown that the fibrosis surrounding the implant would keep it from moving. However, the pharmaceutical company hadn't assessed the mechanical integrity of the spring weld, which was made of silver-tin.

During their analysis in collaboration with the Minapath laboratory, Trunfio-Sfarghiu's team found that the weld had corroded and that tin particles had been released into the subjects' bodies. "The study included about 40 women, and we found tin in all of them," said Trunfio-Sfarghiu.

This weld corrosion has several possible consequences. "When the implant degrades, it can travel anywhere in the pelvis, like a needle moving through the body with no apparent destination. The surgeons who operate to remove it describe similar surgeries in military medicine when the patient has been hit by a bullet!"

Organotin Toxicity

Although tin is not especially toxic for the body when ingested, it can bind to organic compounds if it passes through to the blood. "When tin binds to a carbon atom, it becomes organotin, a neurotoxin," said Trunfio-Sfarghiu.

She believes that this organotin can travel to the brain and trigger symptoms like those found in patients with Essure implants. "For the time being, there is insufficient data to assert that we found organotin in all subjects. Another more in-depth study would be needed to assess migration to the brain. For the past 2 years, we have tried to obtain academic funding to continue our research, so far without success. Academic and political authorities seem to be a bit scared of what we've found," said Trunfio-Sfarghiu.

For her, "it's how the implant was marketed that is problematic. The implant was designed to create local inflammation, inflammation in itself being difficult to control. Some women need to have their entire uterus and ovaries removed to resolve problems caused by the implant."

Harm in the United States

Trunfio-Sfarghiu's research has helped American victims obtain acknowledgment of their suffering in the United States. "But the harm caused to women by defective implants has yet to be acknowledged in France," she added.

She explained that Essure was recalled in 2017 because sales were poor, not because it was deemed dangerous. Her conclusion? "No implant that creates inflammation should be authorized, especially if there is a surgical alternative, which there is here: tubal ligation."

https://www.medscape.com/viewarticle/974841

Long COVID Neuropsychiatric Deficits Greater Than Expected

 Patients experiencing brain fog and other persistent symptoms of long COVID show significant deficits on neuropsychiatric testing that correspond with prior acute COVID-19 infection, adding to mounting evidence of the significant toll the chronic condition can have on mental health.

Dr Sean Lynch

"Many clinicians have observed the symptoms we describe in this study, however this report is among the first which identify the specific deficits using neuropsychological testing to better characterize the syndrome," Sean T. Lynch, MD, first author of a study on the issue presented at the annual meeting of the American Psychiatric Association, said in an interview.

Lynch, of the department of psychiatry, Westchester Medical Center Health System, Valhalla, N.Y., and his colleagues enrolled 60 participants who had experienced acute COVID-19 disease 6-8 months earlier and had undergone neuropsychological, psychiatric, medical, functional, and quality-of-life assessments. Results from the study were published online in the Journal of the Academy of Consultation–Liaison Psychiatry (2022 Jan 25. doi: 10.1016/j.jaclp.2022.01.003).

Among the study participants, 32 were seeking treatment for brain fog in a clinical program for survivors of COVID-19, while the remaining 28 were part of an ongoing longitudinal investigation of neuropsychological, medical, and psychiatric sequelae of COVID-19, but were not seeking care for the persistent symptoms.

Assessments for neurocognitive impairment included a battery of tests used in infectious and other diseases, including the Test of Premorbid Function, the Patient Assessment of Own Function, the Trail Making Test parts A and B, the Stroop Color and Word Test, and others.

Overall, the battery of assessments showed that 37 (62%) of participants had neuropsychological test impairment, with results below the 16th percentile in two tests, while 16 (27%) showed scores indicative of severe impairment (below the second percentile in at least one test and below the 16th percentile in one test).

Those reporting brain fog had scores that were even lower than expected on tests of attention, processing speed, memory, and executive function. And among those reporting brain fog, significantly more had scores reflecting severe impairment compared with the controls (38% vs. 14%; P < .04).

"Based on what we've observed in our patients and what others have previously reported, we did expect to find some impairment in this study sample," Lynch noted.

"However, we were surprised to find that 27% of the study sample had extremely low neuropsychological test scores, meaning that they scored at least two standard deviations below the expected score on at least one neuropsychological test based on their age and level of education."

The brain fog group also reported significantly higher levels of depression, fatigue, PTSD, and functional difficulties, and lower quality of life.

Severe impairment on the neuropsychological tests correlated with the extent of acute COVID-19 symptoms, as well as depression scores, number of medical comorbidities, and subjective cognitive complaints.

An analysis of serum levels of the inflammatory markers among 50 of the 60 participants showed that 45% of the patients had an elevated IL-6, 20% had elevated TNF-alpha, and 41% had elevated CRP, compared with reference ranges.

IL-6 levels were found to correlate with acute COVID-19 symptoms, the number of medical comorbidities, fatigue, and measures of executive function, while C-reactive protein (CRP) correlated with current COVID-19 symptoms and depression scores.

In terms of clinical factors that might predict low neuropsychological test scores, Lynch noted that the "markers that we found to be significant included severity of acute COVID-19 illness, current post-COVID-19 symptoms, measures of depression and anxiety, level of fatigue, and number of medical comorbidities."

Lynch noted that the ongoing study will include up to 18-month follow-ups that are currently underway. "The [follow-ups] will examine if symptoms improve over time and evaluate if any intervention that took place was successful," he said.

Survey Supports Findings

The detrimental effects of mental health symptoms in long COVID were further supported in another study at the APA meeting, an online survey of 787 survivors of acute COVID-19.

In the community survey, presented by Michael Van Ameringen, MD, a professor in the department of psychiatry and behavioral neurosciences at McMaster University, in Hamilton, Ont., all respondents (100%) reported having persistent symptoms of the virus, and as many as 68% indicated that they had not returned to normal functioning, despite only 15% of the respondents having been hospitalized with COVID-19.

A large proportion showed significant depression, anxiety, and posttraumatic stress disorder (PTSD), and the most commonly reported persistent symptoms were fatigue in 75.9% of respondents, brain fog in 67.9%, concentration difficulties in 61.1%, and weakness in 51.2%.

As many as 88.2% of patients said they experienced persistent neurocognitive symptoms, with poor memory and concentration; 56% reported problems with word finding; and 54.1% had slowed thinking.

The respondents showed high rates of anxiety (41.7%) as well as depression (61.4%) as determined by scores above 9 on the Generalized Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaires (PHQ-9).

As many as 40.5% of respondents showed probable PTSD, with scores above 30 on the PTSD checklist (PCL-5). Their mean resilience score on the Brief Resilient Coping Scale was 13.5, suggesting low resilience.

Among the respondents, 43.3% said they had received past treatment for mental health, while 33.5% were currently receiving mental health treatment.

Ameringen noted the important limitation of the study being an online survey with no control group, but said the responses nevertheless raise the question of the role of prior psychiatric disorders in long COVID.

"In our sample, 40% of respondents had a past psychiatric history, so you wonder if that also makes you vulnerable to long COVID," he said in an interview.

"About a third were getting psychiatric help, but I think the more impaired you are, the more likely you are to seek help."

Those who were hospitalized with COVID-19 were at a higher risk of PTSD compared with those not hospitalized (P < .001), as were those under the age of 30 (P < .05) or between 31 and 50 vs. over 50 (P < .01).

Ameringen noted that the survey's high rate of subjects who had not returned to normal functioning was especially striking.

"This is not a minor issue – these are people who are no longer functioning in society," he said.

In Pandemics, the Brain Tends to Be "Overlooked"

Further addressing the neurological effects of COVID-19 at the APA meeting, Avindra Nath, MD, clinical director of the National Institutes of Neurologic Disorders and Stroke in Bethesda, Md., noted that the persisting cognitive and psychiatric symptoms after illness, such as brain fog and depression and anxiety, are not necessarily unique to COVID-19.

Dr Avindra Nath

"We have seen this before," he said. "There have been at least seven or eight human coronaviruses, and the interesting thing is each one affects the brain and causes neurological complications."

The effects are classified differently and have slightly different receptors, "but the consequences are the same."

Of note, however, research published in The Lancet Psychiatry (2021 May. doi: 10.1016/S2215-0366[21]00084-5) revealed that symptoms such as dementia, mood, and anxiety are significantly higher after COVID-19 compared with other respiratory infections, with the differences increasing at 180 days since the index event.

Nath noted that, over the decades, he has observed that in pandemics "the brain tends to get overlooked." He explained that "what can be most important in the end is what happened in the brain, because those are the things that really cause the long-term consequences."

"These patients are depressed; they have dementia, they have brain fog, and even now that we recognize these issues, we haven't done a very good job of studying them," he said. "There's so much we still don't know, and a lot of patients are left with these symptoms and nowhere to go."

Lynch, Ameringen, and Nath had no disclosures to report.

https://www.medscape.com/viewarticle/974840

Amgen Reports Positive Phase 2 Study of Olpasiran in Lipoprotein(a)

 Amgen Inc. on Tuesday reported positive topline data from a Phase 2 study evaluating olpasiran in the reduction of lipoprotein(a), reported to be an independent risk factor for cardiovascular disease.

The Thousand Oaks, Calif., biotechnology company said the study showed significant, sustained reduction in lipoprotein(a) in adults with levels over 150 nmol/L and evidence of atherosclerotic cardiovascular disease.

Olpasiran is designed to lower the body's production of apolipoprotein(a), a key component of lipoprotein(a) that has been associated with an increased risk of cardiovascular events.

Amgen said olpasiran showed a reduction from baseline in lipoprotein(a) of up to or greater than 90% at week 36, the primary endpoint, and week 48, the end of the treatment period, for the majority of doses, adding that no new safety concerns were identified.

https://www.marketscreener.com/quote/stock/AMGEN-INC-4847/news/Amgen-Reports-Positive-Phase-2-Study-of-Olpasiran-in-Lipoprotein-a-40597745/

Takeda says drugmakers could cut prices in face of global crises

The head of Asia’s largest pharmaceutical company said the risk of a global recession, along with the impact of Covid-19 and the war in Ukraine, could force the industry to cut drug prices. Christophe Weber, chief executive of Takeda, which is based in Tokyo, said pressure on government healthcare budgets had increased this year due to the costs of combating multiple crises, such as the pandemic, the Russia-Ukraine war and investments related to climate change.

 “Energy and food costs, together with supply chain constraints, have led to significantly higher inflation and economists are pointing to a heightened risk of a looming recession, particularly as the forces driving inflation show no signs of abating,” he said in a letter to shareholders. “This perfect storm scenario will have an impact on investment in innovation and could accelerate downward pressure on drug pricing.” 

 Weber said the crisis in Ukraine was a reminder that companies operated in a “very uncertain and politically divided” world and Takeda is “scenario planning” to ensure it can react to any situation. 

 The last global recession in 2008 prompted European nations to implement a series of pricing and regulatory reforms, which drove down the value of drug sales despite a slight increase in volumes between 2008 and 2011, according to a study of eight EU states by the World Health Organization. Prices of branded drugs fell by an average of 2 per cent to 9 per cent per year between 2017 to 2021 in five of the six largest pharmaceutical markets — Japan, Germany, Australia, Spain and France — according to research by GlobalData, a consultancy. However, in the US — by far the world’s most valuable pharmaceutical market — list prices of patented drugs rose by an average of 18 per cent per year between 2017 and 2021.

 List prices are the prices that manufacturers initially set for a drug. In the US, pharmaceutical companies often offer rebates and discounts on products that can cut the final cost to patients.

 Evan Seigerman, biopharma analyst at BMO Capital Markets, said the drop in list prices in markets outside the US is not surprising because most governments negotiate procurement directly with industry and so can exert downward pressure on prices.

 “Depending on the state of any recession, if there is a big strain on government budgets then you could see increased pricing pressure,” he said.

 Seigerman said pricing pressure in the US would probably be less pronounced due to the political difficulties in passing drug price reform legislation in Congress. 

 The Biden administration’s efforts to pass drug pricing reforms, which include allowing the government’s health insurance scheme Medicare to negotiate some drug prices, have foundered in Congress. However, this week senator Joe Manchin, a Democratic senator who helped block the proposed reforms last year, suggested that drug price reforms could be legislated later this year as part of a broader legislative package.

 “There is no reason in the world why we can’t negotiate for Medicare, having better pricing, and also for different types of medicines,” he told an event at Davos last week.

 Takeda’s letter to shareholders also warns global authorities risk remaining in “a state of inertia” when it comes to preparing for the next pandemic. Not enough work has been done to create global stockpiles of protective equipment, medical devices, vaccines and treatments for rapid deployment in a crisis, it said. There is a lack of funding to better understand zoonotic diseases and the current crop of Covid vaccines may not be good enough, according to Weber.

 “A reliance on a consistent pattern of boosters could ultimately diminish adoption — and we are already seeing booster adoption plateau in some countries,” he said. “We should accumulate more clinical data and real-world evidence to establish the long-term benefit/risk profile of multiple booster doses among the broader population in a short period of time, a practice never done before with any vaccine.”

https://www.ft.com/content/492beff8-a077-421e-8da9-faf378e15175

UK recommends people who test positive for monkeypox abstain from sex

 The UK Health Security Agency on Monday issued guidance recommending that people who test positive monkeypox abstain from sexual activity while they are symptomatic.

“People with possible, probable or confirmed monkeypox should avoid contact with other people until their lesions have healed and the scabs have dried off,” the agency said in its guidance. “Cases should also abstain from sex while symptomatic, including the period of early symptom onset, and while lesions are present.”

Monkeypox is primarily spread through prolonged skin-to-skin contact with an infectious person — not just sexual. It typically causes lesions to form on an individual’s face and body.

The agency noted that there is currently “no available evidence of monkeypox in genital excretions,” but advised that condoms still be used for eight weeks after infection as a “precaution.”

An individual who contracts monkeypox is generally considered to no longer be infectious once their skin lesions scab over and are fully healed.

As of Monday, 183 monkeypox cases have been confirmed in the U.K. In the U.S., the Centers for Disease Control and Prevention has identified 10 cases of monkeypox.

When monkeypox cases were first identified in Europe, health authorities observed that many cases were occurring among men who have sex with men. Experts have since speculated that the outbreaks were linked to raves in Spain and Belgium.

Monkeypox can also be spread through contact with an infectious individual’s clothing or bedsheets. Standard cleaning methods such as handwashing and washing linens with detergent in a washing machine reduces the risk of transmission.

People in the same household as someone infected with monkeypox are also at a higher risk of contracting the pathogen. Infections usually last between two and four weeks and the mortality rate for the disease is very low.

Vaccines and antivirals believed to be effective against monkeypox have been mobilized in numerous countries like the U.S., with orders placed for more antivirals to be produced.

Ruth Milton, senior medical advisor and monkeypox strategic response director for the British health agency, stressed that the risk monkeypox poss to the U.K. public still remains low.

https://thehill.com/policy/healthcare/3506947-uk-recommends-people-who-test-positive-for-monkeypox-abstain-from-sex/