Novo Nordisk shares fall after media report on quality lapses at US plant

 Novo Nordisk's shares fell on Monday after financial news agency MarketWire reported that U.S. drug regulators had recently issued a report detailing quality control lapses at the group's Clayton, North Carolina plant, citing sources.

Reuters was not immediately able to authenticate the report. Novo Nordisk declined to comment on the report, but said in an emailed statement that the site was "running and producing for the market".

Clayton is a major site for the company's production of its active pharmaceutical ingredients, including semaglutide, which is the drug used in its hugely popular weight-loss drug Wegovy and type 2 diabetes drug Ozempic.

Shares in the company were down 3% at 1133 GMT.

MarketWire did not specify when the FDA inspection occurred.

Flags are seen outside Novo Nordisk headquarters in Copenhagen, Denmark, Feb. 5, 2020.  (REUTERS/Jacob Gronholt-Pedersen/File Photo / Reuters)

The FDA did not immediately respond to a request for comment from Reuters, and does not typically comment on individual inspections.

The FDA's inspection dashboard, a public website, was not currently listing any inspections as having occurred this year, but the dashboard is not a comprehensive record of all its inspections.

MarketWire's article on Monday stated that FDA inspectors had issued a Form 483 following their inspection. According to the FDA, a Form 483 is a type of agency report containing "observations" that FDA inspectors "deem to be objectionable".

https://www.foxbusiness.com/markets/novo-nordisk-shares-fall-media-report-quality-lapses-us-plant

Lantern Cleared for Phase 1 Initiation for Drug Candidate LP-284 in Non-Hodgkin’s Lymphomas

 

• This is the second IND Clearance over the last 100 days for drug candidates that are being developed using guidance from Lantern’s AI Platform, RADR^®.
• LP-284 is the second of Lantern’s synthetic-lethal franchise of molecules that have shown to be synthetically lethal in DNA damage repair deficient cancers and are entering into first-in-human clinical trials.
• Lantern estimates that LP-284 can have the potential to improve outcomes for 40,000 to 80,000 patients with blood cancers annually, with a global annual market potential of $4 Billion USD.

https://www.biospace.com/article/releases/lantern-pharma-receives-ind-clearance-from-fda-enabling-phase-1-initiation-for-drug-candidate-lp-284-in-non-hodgkin-s-lymphomas/

Anthos mid-stage trial stopped early due to "overwhelming" effect

 A novel antibody developed by Anthos Therapeutics, a cardiovascular specialist founded by Blackstone Life Sciences, has performed well in a Phase II trial.

Abelacimab is a novel monoclonal antibody under development for people with atrial fibrillation. The therapy locks Factor XI in the inactive state, resulting in dual inhibitory activity.

Scientists at the company believe this approach may provide an effective treatment strategy for a certain group of people who can benefit from the protection of an anticoagulant.

Encouraging data

Results show that the mid-stage AZALEA-TIMI 71 trial, which has enrolled over 1,200 patients with atrial fibrillation at moderate-to-high risk of stroke, met its primary endpoint at an interim analysis.

The firm said data monitors had advised to stop the trial early, “due to an overwhelming reduction in the composite of major and clinically relevant non-major bleeding in patients taking abelacimab compared with patients taking rivaroxaban,” a leading standard-of-care direct oral anticoagulant.

The data make abelacimab the first and only Factor XI inhibitor to show this level of reduction in major bleeding compared to a direct oral anticoagulant (DOAC).

Chief medical officer Dan Bloomfield said: “Given AZALEA-TIMI 71’s overwhelming reduction in bleeding, together with an 80% reduction in thrombosis demonstrated in our earlier VTE study, abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”

He added: “If approved, more patients with atrial fibrillation could be treated effectively and safely, with a much lower risk of bleeding with abelacimab as compared to a DOAC.”

In the USA, the candidate has been granted a Fast-Track designation for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Full results from the trial will be presented at an upcoming scientific congress.

https://www.thepharmaletter.com/article/mid-stage-trial-stopped-early-due-to-overwhelming-effect

Pediatricians' group warns against keto diet for kids with diabetes

 Low-carb diets may be all the rage, but they're not for kids with diabetes, according to the American Academy of Pediatrics (AAP).

In a new report, the AAP says that low-carbohydrate diets cannot be recommended for children or teenagers with either type 1 or type 2 diabetes. That's because there's little evidence they're helpful, but there are concerns about restricting kids' diets to that degree.

Instead, the AAP encourages families to focus on cutting out "bad" carbs: sugary drinks, sweets and other processed foods that are low in nutrients. Just as important, kids should get enough healthy carbs, including vegetables, beans and fiber-rich grains.

The "keto" diet and similar ones popular among adults can put very strict limits on carbs, with a ceiling as low as 20 grams per day—equivalent to a half-cup of white rice.

A big concern is that low-carb diets will shortchange kids on nutrients during critical periods of development, said Amy Reed, a pediatric dietitian with Cincinnati Children's Hospital Medical Center.

Reed, who was not involved in the AAP report, said she agrees with its recommendations.

"The focus should be on healthy eating, rather than restriction," said Reed, who is also a spokeswoman for the Academy of Nutrition and Dietetics.

Diabetes exists in different forms: Type 1 diabetes arises from an immune system attack on the pancreatic cells that produce insulin, a hormone that regulates blood sugar. In type 2 diabetes, which is often associated with obesity, the body loses its ability to properly use insulin.

As a result, blood sugar levels soar. Kids with type 1 need to take daily insulin injections or wear an insulin pump. Those with type 2 may need medication or help with weight loss. In either case, attention to diet is key.

Some doctors recommend low-carb diets for adults with diabetes, while many popular diets—and celebrities—tout carb-cutting for weight loss.

So some parents may be interested in going low-carb to manage their kids' diabetes, said Dr. Tamara Hannon, one of the authors on the AAP report.

"But it doesn't have to be extreme, it just has to be reasonable," said Hannon, a pediatric endocrinologist at Riley Children's Health in Indianapolis. "Wherever you can, decrease sugary foods."

Eliminating sugar-sweetened drinks, including juices, is a great way to start, Hannon said.

"It can be hard for families to eat well on a budget," she noted. "But cutting out sugary drinks costs nothing."

Nor does it come with the potential risks of low-carb diets for kids. According to the AAP, those include nutrient deficiencies, stunted growth or bone development, and steeping kids in the "diet culture" that could lead to body dissatisfaction and eating disorders.

If parents do, however, want to try a low-carb diet for managing their child's diabetes, the AAP urges them to work with their health care providers. The group recommends extra monitoring of kids' growth, bone health, nutritional status and more.

Not all U.S. families, though, have access to such "gold standard" care, Hannon said, especially in parts of the country where specialists are in short supply.

In general, the AAP recommends that kids with diabetes or "prediabetes"—abnormal blood sugar levels that may precede type 2 diabetes—follow the same diet guidelines in place for all children aged 4 to 18:

• About 10% to 30% of daily calories should come from protein.
• Another 25% to 35% should come from fat—mainly unsaturated fats from sources like plant oils and nuts.
• The remaining 45% to 65% should come from carbohydrates, mainly fruits, vegetables, beans, dairy products and high-fiber grains.

Reed pointed out that the typical American kid is not getting enough fiber, and that a low-carb diet would make that even worse.

Fiber, she said, can be helpful in managing blood sugar levels, as it slows digestion.

For families on a budget, Reed noted that frozen or canned vegetables are not only fine, but in some cases may be even more nutrient-packed than their fresh counterparts. There are also kid-friendly ways to fit in more healthy carbs, she said—like making tacos with meat, beans and vegetables.

But kids' diets are not only the responsibility of parents, Hannon stressed. American society, she said, makes nutritionally dubious choices easy and healthy ones tougher—especially for lower-income families.

One way pediatricians can help, the AAP says, is by encouraging families who qualify for federal nutrition assistance to enroll.

The report was published online Sept. 18 in the AAP's journal Pediatrics.

More information: Anna Neyman et al, Low-Carbohydrate Diets in Children and Adolescents With or at Risk for Diabetes, Pediatrics (2023). DOI: 10.1542/peds.2023-063755

https://medicalxpress.com/news/2023-09-pediatricians-group-keto-diet-kids.html

Dental issues plague America's nursing home residents

 Good oral health is one of the keys to healthy aging, but a sobering new study shows that many U.S. nursing home residents have significant dental issues.

Close to two in every 10 residents have missing teeth, about 8% have broken teeth/cavities and another 11% report pain while chewing, researchers found.

"Inadequate oral health has far-reaching consequences that extend beyond the mouth, profoundly affecting one's overall well-being, nutritional intake and general health," said study author Dr. Natalia Chalmers, chief dental officer at the U.S. Centers for Medicare & Medicaid Services (CMS), in Baltimore.

Poor oral health can hinder a person's ability to chew properly, which can eventually lead to malnutrition. In addition, bacteria from gum infections can enter the bloodstream, increasing the risk for heart disease and other conditions, she explained.

"This interconnected relationship between oral health and overall health underscores the importance of maintaining a healthy mouth," Chalmers said.

For the study, researchers analyzed data on the oral health of Medicare beneficiaries living in CMS-certified nursing homes in 2020. Overall, having no natural teeth or tooth fragments were the most common dental problems in seniors, followed by cavities or broken natural teeth, pain, difficulty chewing, broken dentures and inflamed gums, among other oral health issues.

There are likely many reasons that dental health declines among nursing home residents, but a main driver is likely the lack of dental coverage. Fully 51% of people who receive Medicare don't have dental coverage, Chalmers noted. That may be because traditional Medicare doesn't cover routine dental services such as exams, cleanings and X-rays, or more expensive services such as fillings, crowns or dentures, so dental insurance has to be paid for separately.

There were some striking disparities seen across racial and ethnic groups. For example, Black people were 16% more likely to have no natural teeth or tooth fragments and 5% more likely to have cavities or broken natural teeth, compared with white people. American Indian or Alaskan Native seniors were also more likely to experience dental issues than white people.

Those nursing home residents with three or more chronic health conditions were more likely to have oral health issues than seniors with no chronic conditions. What's more, people in rural nursing homes had higher odds of experiencing dental problems than people in urban nursing homes, the investigators found.

"If your family member resides in a nursing home, it's essential to establish clear communication with the facility's staff regarding their oral care routine, and preferences regarding assistance and toothbrushes and toothpaste, such as whether they prefer manual or electric toothbrushes, and what fluoridated toothpaste they use," said Chalmers. "You should ensure that the staff is well-informed about your loved one's dentist and the designated contact person in emergencies."

The findings were published online Sept. 12 in JAMA Network Open.

Dr. Bruce Dye is chair of the department of community dentistry and population health at the University of Colorado School of Dental Medicine in Aurora. He wrote an editorial accompanying the new study.

"We know oral health is associated with many chronic diseases, and with more seniors living longer with more chronic diseases, having poor oral health reduces the likelihood of many of them enjoying optimal health and well-being," Dye said.

It's time to take steps to ensure that seniors can access dental care, including making dental insurance more affordable, he added.

There are also things a loved one can do to advocate for oral health among family and friends in nursing homes, Dye suggested.

"Develop an ongoing relationship with the nursing staff caring for [your] loved one and with the director of nursing," he said. In most nursing homes, the director of nursing works directly with staff and the consulting dentist.

New York City dentist Dr. Saul Pressner agreed that more efforts are needed to improve access to dental care for folks in nursing homes. He is the president of the Academy of Biomimetic Dentistry, which is a type of tooth-conserving dentistry that focuses on preserving natural teeth.

"Having a dental benefit for all Medicare recipients would go a long way toward addressing the lack of access to good dental care in the nursing home population," said Pressner.

In addition, a dedicated dental treatment area in nursing homes would make it easier for residents to seek care. Other easy fixes can include utilizing auxiliary staff to help residents with their oral care.

"Visits by dentists to conduct oral cancer exams would help in early detection of diseases, which if caught early can prevent further systemic disease issues," he suggested. "Proper nutrition in nursing homes along with good home care instruction for oral health would immensely help in minimizing dental disease."

More information: Steffany Chamut et al, Oral Health Among Medicare Beneficiaries in Nursing Homes, JAMA Network Open (2023). DOI: 10.1001/jamanetworkopen.2023.33367

https://medicalxpress.com/news/2023-09-dental-issues-plague-america-nursing.html

Cell therapy can reduce risk of death from COVID-19 by 60%, study finds

 The use of cell therapy to treat COVID-19 patients can reduce the risk of death from the disease by 60%, according to a systematic review and meta-analysis conducted by researchers at the University of São Paulo (USP) in Brazil, in partnership with colleagues in Germany and the United States.

Their findings are reported in an article published in the journal Frontiers in Immunology.

The review covers 195 clinical trials of advanced cell therapies targeting COVID-19 that were conducted in 30 countries between January 2020 and December 2021, as well as 26 trials with outcomes published by July 2022.

Cell therapy has come into increasingly frequent use in recent years to treat several diseases, especially cancer. It consists basically of introducing healthy cells into the patient's organism in order to restore or alter certain sets of cells, carry a therapy through the body, or modulate the function of diseased cells.

The technique uses stem cells and derivatives from the patient (autologous) or from a donor (allogenic). The cells are cultured or modified in the laboratory before being administered. According to the article, the cell types most frequently used in clinical trials relating to treatment of COVID-19 in the period were multipotent mesenchymal stem (stromal) cells from connective tissue, used in 72% of the studies reviewed; natural killer cells from lymphoblasts, used in 9%; and mononuclear cells from blood, used in 6%.

"Cell therapy has advanced significantly in recent years and has been used to treat cancer and auto-immune, heart and infectious diseases. During the pandemic, it was used to treat COVID-19 in several clinical trials," said Otávio Cabral-Marques, a professor at USP's Medical School and coordinator of the study.

"Our study is the first to review all the information on these experiences scattered around the world and to verify by means of a meta-analysis [a statistical method of aggregating data from many independent studies] how cell therapy functions when used to treat COVID-19 and related complications," he continued.

Stem cell therapy and models involving organoids derived from stem cells drew a great deal of attention as novel methods for treating and studying COVID-19 during the pandemic, he noted, given the significant immune regulatory power and tissue repair functions of stem cells, especially the mesenchymal variety. In the case of the lungs, for example, clinical trials have shown to a greater or lesser extent that advanced cell therapy can limit the severity of the inflammatory response in COVID-19 patients, reduce pulmonary damage, improve lung function and help combat fibrosis.

Despite the attention paid to cell therapy, the real protection assured by vaccination should be stressed, according to Cabral-Marques. "Although all these studies have shown that advanced cell therapy could become established soon as an important adjunct treatment for these patients, prevention of the disease by vaccination remains the best protection," he said.

The clinical trials involving advanced cell therapy for COVID-19 analyzed by the authors of the review article were conducted in 30 countries, mainly the United States, China, Iran and Spain. They were highly heterogeneous, however, with widely varying numbers of participants, designs and methodologies, so for meta-analysis purposes the researchers created a specially curated COVID-19 trials database at CellTrials.org with several quality refinements, such as inclusion of trials from all national registries, exclusion of false positives on keywords, and exclusion of double counting of the same trials.

The authors also note differences in terms of the phases of trials. In many countries, especially in Europe, strict regulation limits the number of human cell therapy products with established safety profiles that can be trialed, and 56% of the trials did not reach phase 2, which typically focuses on determining safety, efficacy and dose-response in a few hundred volunteers with the disease. Another limitation was that 31% of the trials analyzed did not have a control group.

"To arrive at such a large reduction in the risk of death, we had to take into account the findings and characteristics of the different studies, as well as making a certain number of corrections and estimates," said Igor Salerno Filgueiras, a Ph.D. candidate and co-author of the article.

"There are techniques to standardize the data, eliminate biases and produce an impartial result, enabling analysts to reach conclusions that often go unnoticed in a specific study but add up to relevant scientific evidence when they are reinforced by other data," said Dennyson Leandro M. Fonseca, another co-author.

Fabrication and clinical delivery methods in studies involving mesenchymal stem cells were "remarkably heterogeneous," according to the article. "The results highlight the important role these cells can play in adjuvant therapies for COVID-19 and the associated complications. However, they also point to a need for better control of key parameters relating to the way the cell therapy products are made if we are to assure comparability between studies," Cabral-Marques said.

More information: Pedro S. Couto et al, Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery, Frontiers in Immunology (2023). DOI: 10.3389/fimmu.2023.1200180

https://medicalxpress.com/news/2023-09-cell-therapy-death-covid-.html

Possible new treatment for triple-negative breast cancer

 Zachary Schug, Ph.D., assistant professor in the Molecular and Cellular Oncogenesis Program of the Ellen and Ronald Caplan Cancer Center at The Wistar Institute, has published a new paper in the journal Nature Cancer. Schug's paper, titled "Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer," demonstrates a double-acting mechanism for fighting a particularly aggressive, difficult-to-treat form of breast cancer. Schug's research shows how silencing a certain gene, ACSS2, may improve existing treatments for patients.

Triple-negative breast cancer, or TNBC, affects 10–15% of patients with breast cancer in the US. TNBC is called "triple-negative" because the cancer lacks an estrogen receptor, a progesterone receptor, and a HER2 (human epidermal growth factor) receptor. The absence of any of these receptors—receptors that when present in other forms of breast cancer, can be effectively targeted during treatment—makes treating TNBC quite difficult, and patients with TNBC have limited treatment options.

TNBC's notorious aggression makes the technical challenge of finding a reliably effective treatment target all the more serious: compared to other breast cancers, TNBC grows faster and resists treatment more stubbornly. All these factors contribute to the fact that TNBC patients suffer from worse prognoses.

But Schug and co-authors have demonstrated the efficacy of a double-acting concept: Silencing the gene ACSS2 impairs TNBC metabolism while simultaneously boosting the immune system's ability to fight it. ACSS2 regulates acetate, a nutrient that cancer cells—and TNBC cells in particular—take advantage of to grow and spread. Schug and his team used two methods to de-activate ACSS2: CRISPR-Cas9 gene editing, and the compound VY-3-135, a potent ACSS2 inhibitor identified by Schug and his colleagues in 2021.

The researchers found that targeting ACSS2 in this preclinical study not only hampered this aggressive cancer's ability to metabolize acetate and grow, it also triggered the immune system to recognize and attack the cancer. Because cancer cells with inhibited ACSS2 can't process acetate very well, the tumor region becomes bathed in acetate, which alerts the immune system of something amiss.

This process of guiding the immune system to the cancer—called "immunosensitization"—has confounded other TNBC researchers. But Schug's approach showed that ACSS2 inhibition immunosensitized against TNBC so well that tumor growth was drastically reduced, even to the point of wiping out the cancer completely in some experiments.

"Basically, we've proved that the immune system can take advantage of acetate that the tumor can't process. It kicks the cancer while it's down," said Schug. "In fact, the immune system does this so well that it remembers how to attack TNBC in the future—even if that tumor's ACSS2 gene is still active."

Another group's different ACSS2-inhibiting approach is in human clinical trials, and Schug's research shows how ACSS2-inhibiting treatment might be able to improve outcomes for patients diagnosed with the infamous TNBC. By testing ACSS2 inhibitors alongside standard anti-breast-cancer chemotherapy, Schug et al. found that ACSS2 inhibition enhanced the treatment's effectiveness.

"We knew that ACSS2 was a promising target for TNBC. Our research shows us how the immune effects of ACSS2 inhibition could eventually be used in for TNBC patients with limited treatment options," said Schug. "More research is needed, but by combining this approach with other cancer therapies, we expect to see big improvements in treating TNBC."

More information: Katelyn D. Miller et al, Acetate acts as a metabolic immunomodulator by bolstering T-cell effector function and potentiating antitumor immunity in breast cancer, Nature Cancer (2023). DOI: 10.1038/s43018-023-00636-6

https://medicalxpress.com/news/2023-09-treatment-triple-negative-breast-cancer.html