Endo adds to opioid settlement-stoked rally

Endo International (ENDP +15.7%) is up on almost triple normal volume, adding to its 19% jump yesterday as investors buy in expecting a workable broad settlement with state and local governments over its role in the opioid epidemic.

Citron Research has added to the renewed animal spirits with a tweet stating that the stock could reach $10 by Monday.

https://seekingalpha.com/news/3506609-endo-adds-opioid-settlement-stoked-rally-16-percent

New Artificial Pancreas Study: ‘A Step Closer to a Brighter Future’

An investigational “artificial pancreas” system is the latest to improve glycemic control in patients with type 1 diabetes in a real-world setting, this time for up to 6 months.
Findings from Protocol 3 of the National Institutes of Health (NIH) funded  International Diabetes Closed Loop (iDCL) trial of Tandem’s t:slim insulin pump with Control-IQ technology were published online October 16 in the New England Journal of Medicine by Sue A. Brown, MD, of the University of Virginia, Charlottesville, and colleagues.
This is the first 6-month study of a closed-loop or artificial pancreas system to include a dedicated control group, according to a Tandem statement.
The closed-loop system, currently under review by the US Food and Drug Administration (FDA), resulted in approximately 2.6 more hours per day spent in the target blood glucose range of 70-180 mg/dL compared with the control group, who used noncommunicating insulin pumps and continuous glucose monitor (CGM) devices.
“Testing the safety and effectiveness of new technologies in real-world settings is critical to prove the usability of these systems by people with diabetes to achieve a better daily control of their blood glucose levels,” study project scientist Guillermo Arreaza-Rubín, MD, director of the Diabetes Technology Program, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), said in an NIH statement.

“Impressive and Clinically Relevant,” but Caveats Remain

The artificial pancreas is an all-in-one system that tracks blood glucose using a CGM and automatically delivers insulin when needed using an insulin pump. It replaces reliance on blood glucose testing by fingerstick or CGM with separate delivery of insulin by pump or multiple daily injections.
One such system, the Medtronic MiniMed 670G artificial pancreas, is already approved by the FDA for use in those age 7 years and older with type 1 diabetes.

These latest iDCL study results are “impressive and clinically relevant,” says Daniela Bruttomesso, MD, PhD, University of Padua, Italy, in an accompanying editorial.
This is because it has “been shown that for each 10% reduction in the time spent in the glucose target range, the risk of development or progression of retinopathy increases by 64% and the risk of development of microalbuminuria by 40%,” she observed.
However, Bruttomesso cautions — as do the authors — that the trial was performed at university-based diabetes centers and the baseline use of sensors and insulin pumps by participants was higher than in the general type 1 diabetes population.
Moreover, the sensor-augmented pump system used in the control group lacked the ability to suspend the pump’s insulin delivery for an impending low glucose, a feature of the currently available Medtronic MiniMed 670G.
Commenting on the first generation of artificial pancreas systems in general, Bruttomesso observes: “We are not there yet, but [the current study provides] a big step toward a brighter future for patients.”

“Time in Range,” Particularly Overnight, Improved

The new study randomized 168 individuals age 14 years and older (mean 33 years) with type 1 diabetes to the closed-loop system (112 patients) or a sensor-augmented insulin pump (56 patients).
The closed-loop system combines a t:slim X2 insulin pump and a Dexcom G6 CGM, along with an algorithm with a dedicated hypoglycemia safety module, automated boluses to correct high blood sugars, and overnight intensification of basal insulin delivery aimed at normalizing morning glucose values.

The system predicts glucose levels 30 minutes ahead and adjusts insulin delivery to help prevent highs and lows, but users must still manually bolus for meals.
At baseline, 79% of patients were already using pumps and 70% were using CGMs.
For the primary endpoint, mean time in target range, the closed-loop group increased from 61% at baseline to 71% by 1 month, and this remained consistent at 6 months, while the time in range percentage remained at 59% in the control group across the study period.

The 11 percentage-point difference (P < .001) corresponded to 2.6 more hours in range per day in the closed-loop group, Brown and colleagues report.
The difference in percentage time-in-range in the closed-loop and control groups was particularly pronounced from midnight to 6:00 am (76% vs 59%), reflecting the “increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors explain.
The overall mean percentage of time spent with glucose levels > 180 mg/dL at 6 months in the closed-loop versus control group was 27% versus 38% (P < .001), corresponding to a mean difference of 2.4 hours per day.

Hemoglobin A1c values were also significantly lower at 6 months in the closed-loop versus control group (7.06% vs 7.39%; P = .001).
Percentage of time with glucose levels < 70 mg/dL were 1.58% and 2.25%, respectively (P < .001), amounting to 13 minutes per day. Glucose levels < 54 mg/dL were rare in both groups but still significantly lower in the closed-loop group (0.29% vs 0.35%; P = .02).
Severe hypoglycemia (requiring assistance) didn’t occur in either group. One participant in the closed-loop group experienced diabetic ketoacidosis resulting from a pump infusion set failure.

Barriers Remain to a Fully Automated Closed-Loop System

“This research shows that this artificial pancreas system has the potential to improve the health of people living with type 1 diabetes, while also potentially lifting much of the burden of care from those with the disease and their caregivers,” notes Arreaza-Rubín.
However, Bruttomesso points out that first-generation closed-loop systems are not without their teething problems.
Although “the closed-loop system is becoming a mature technology ready for practical use…there are a variety of barriers to a fully automated closed-loop system,” including slow subcutaneous absorption of insulin, insufficient sensor accuracy, and algorithms that fall short of accounting for everyday insulin needs, she points out.
Indeed, one study reported earlier this year showed that over a third of patients using the currently available Medtronic MiniMed 670G quit using the system within 9 months because of technical difficulties.
And Bruttomesso adds, “Whether closed-loop systems can be used in higher-risk patients, such as those with impaired awareness of hypoglycemia, also remains a pressing issue.”
“Cost-effectiveness, user acceptance, and training of both patients and healthcare professionals also need to be addressed,” she emphasizes.
“It is clear that patients would appreciate wearing devices that require minimal interaction, leading to a more carefree lifestyle,” she concludes.
The study was supported by a grant from the NIDDK and University of Virginia. Brown has reported receiving grant support and supplies, paid to her institution, from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Bruttomesso has reported no relevant financial relationships.
N Engl J Med. Published online October 16, 2019. Abstract, Editorial
https://www.medscape.com/viewarticle/919986#vp_1

Sports Participation a Big Win for Kids’ Mental Health

Children who play sports are less likely to experience withdrawn and depressive symptoms compared with their counterparts who do not engage in sports, new research suggests.
Investigators at Boston University School of Medicine found kids who participated in one or fewer sports had a higher incidence of withdrawn behavior and depressive symptoms, suggesting playing two or more sports “may be the magic number.”
“We found a statistically significant difference between children who played two or more sports vs those who played zero or one,” study investigator Punit Matta, MS, told Medscape Medical News.
The findings were presented here at the American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting.

A Promising Early Intervention

The existing literature shows an association between sports participation and mental-health benefits in adolescents and adults. Nevertheless, few studies have examined the potential link in children younger than 12.
The investigators hypothesized that encouraging children to participate in sports may be an effective early intervention for at-risk children. This led them to investigate the association between sports participation in children and symptoms of mental illness.
“Originally, we were interested in examining the relationship between attention problems and physical activity,” said study coinvestigator Andrea Spencer, MD. “Then we realized that the Child Behavior Checklist [CBCL] dataset would allow us to look at this question for a much wider set of symptoms. And what we found was really interesting.”

The study was a secondary analysis of data from 206 children (ages 6-11; 51% male; 85% Hispanic or Latino). Parents of the children had all completed a CBCL during a well-child visit at an urban community health center between January 2013 and June 2015.
“The Hispanic or Latino population is one of the gaps in the literature that we identified,” said Spencer. “Many of the studies that have looked into this question have focused on Caucasian samples, as well as people who are older, such as adolescents and adults.”
The researchers measured sport count by using CBCL items that ask guardians to list the sports their child plays. They measured domains of psychiatric symptoms by using the eight syndrome scales of the CBCL: anxious/depressed; withdrawn/depressed; somatic complaints; social problems; thought problems; attention problems; rule-breaking behavior; and aggressive behavior.
Linear regression analyses determined the association, if any, between measures of mental illness symptoms (total number of CBCL syndrome scale elevations and individual syndrome scale elevations) and sports participation.
After controlling for covariates, investigators found a higher number of sports was significantly associated with lower scores on with Withdrawn/Depressed subscale (beta estimate, -1.044; t value, -2.37; P = .0186). Nevertheless, the other CBCL syndrome subscales were not significantly associated with sport count (all P < .05).
Interestingly, both age and ethnicity were also significantly associated with the Withdrawn/Depressed subscale. Indeed, older children had higher scores on the subscale (beta estimate, 0.958; t value, 3.05; P =.0026). Contrarily, Latino children had lower Withdrawn/Depression subscale scores compared to non-Latino children (beta estimate, 3.158; t value, 2.10; P =.0368)
In a post-hoc analysis, children whose parents reported one or fewer sports had twice the odds of having clinically elevated Withdrawn/Depressed syndrome scores on the CBCL than those playing two or more sports (odds ratio 2.339; 95% confidence interval, 1.127 – 4.853).

These findings may help primary care physicians identify a promising early intervention strategy for children with withdrawn, depressive symptoms.
“There’s been a huge movement in primary care right now to screen for social determinants and connect children with resources. But nobody is asking these children systematically about sports participation,” said Spencer.
“The most compelling thing I can think of is to suggest sports as the intervention,” Matta added. “Because one of the big challenges with treating children this age is that you don’t want to give them powerful drugs and you don’t know how therapy will work.”

Confidence, Relationship Builder

Commenting on the findings for Medscape Medical News, Samantha Kennedy, DO, assistant professor of psychiatry at Michigan State University in East Lansing, said she has personally witnessed the benefits of sport in her patient population.
“Perhaps one theory behind the results is that children involved in more sports participate year-round, rather than just for one season,” said Kennedy.
Yet as vital as physical activity may be in these children, Kennedy also saw benefit in the camaraderie that accompanies sports participation.

“The children are instantly with a group of people and have something in common,” she explained. “So it can be really easy to start talking to the other kids on the team, and from there they can grow confidence to talk about things other than sports.
“What’s more, playing sports keeps kids busy, so they’re not using substances or out doing other things they shouldn’t be doing.”
Spencer concluded that the findings might spur insurers to broaden their coverage.
“Ultimately, it may be less expensive for the health insurance companies to pay for a child with initial symptoms to go into sports, rather than wait until they’re 12 or 13 [years old] and need an intervention that’s more involved and more expensive,” she said.
“It’s all about expanding the modes of treatment that pediatricians can provide to children at risk,” Matta added.
The research was supported by the Louis Gerstner Foundation. Matta, Spencer, and Kennedy have disclosed no relevant financial relationships.
American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting: Abstract 2.26. Presented October 16, 2019.
https://www.medscape.com/viewarticle/919998#vp_1

Syros Pharma bails on cancer candidate SY-1365

Citing the greater anti-tumor activity of CDK7 inhibitor SY-5609 and its more flexible oral route of administration, Syros Pharmaceuticals (SYRS -27.5%) has decided to terminate development of intravenously administered CDK7 inhibitor SY-1365. A Phase 1 study should launch next quarter.

Investors appear to be reacting to the abrupt switch and longer timeline since the company was supposed to release data from a Phase 1 trial of SY-1365 this quarter.

https://seekingalpha.com/news/3506555-syros-pharma-bails-cancer-candidate-syminus-1365-shares-28-percent

FDA OKs expanded use of Roche flu med Xofluza

The FDA approves Roche (OTCQX:RHHBY +2%) unit Genentech’s supplemental marketing application for Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza in people at least 12 years old who have been symptomatic for no more than 48 hours and are at high risk of developing flu-related complications.

The agency first approved the polymerase acidic endonuclease inhibitor a year ago for the acute treatment of uncomplicated flu in otherwise healthy people at least 12 years old who have been symptomatic for no more than 48 hours.

https://seekingalpha.com/news/3506585-fda-oks-expanded-use-roche-flu-med-xofluza

Unlock your dog’s genetic secrets with these DNA test kits

If you’re one of those people who treats your pup like a person, you probably want to learn as much about them as possible. And thanks to DNA testing, it’s easier than ever to unlock all your four-legged friend’s genetic secrets.
You’ve probably already tested your own DNA to learn about your personal ancestry, but now it’s time to put man’s best friend under the microscope. You’ll learn your dog’s actual breed, health concerns, potential allergies and diseases to look out for and more. Heck, you may even find out a relative of theirs is living near your home. Fur baby reunion, anyone?
Ready to gain a better understanding of your four-legged friend? Pick up one of these dog DNA test kits on sale for up to 30% off.

Allergy Test My Pet Kit

While it’s undeniably adorable when your pup sneezes, rubs its face, sniffles and snores, those could be signs of an allergy or sensitivity to something in or around your home. This Allergy Test My Pet Kit can help you identify exactly what it is that’s bothering them. Just swab the inside of your pet’s cheeks, just like you would for a human DNA test kit, and send it over to the lab for analysis. The experts will test the sample and report for more than 100 items that are potentially causing issues – from laundry and cleaning products to tobacco and even foods. You’ll even learn which foods are best for your doggo’s diet.
This test kit usually costs $99, but you can pick one up today for $69 – 30% off the retail value.

Embark Dog DNA Test Kit

The Embark Dog DNA Test Kit is a Cornell University College of Veterinary Medicine research partner and is regarded as the most accurate and highest reviewed dog DNA kit on the market. With just a simple cheek swab, you can gain a deeper understanding of your pup’s breed, ancestry and relatives. It uses a research-grade DNA genotyping platform and looks at 200,000 genetic markers to help you dive into who your dog truly is. You’ll uncover secrets of your pup’s family tree, tracing all the way back to their great grandparents, discover their relatives and connect with them and put together all the pieces of your dog’s puzzle.
Typically retailing for $199, you can unlock your dog’s genetic secrets with Embark for just $175 now.

DNA My Dog Breed Identification Test

Is Max really part lab? Or is he retriever? Or maybe part terrier? With the DNA My Dog Breed Identification Test, you can finally stop wondering. Like a human DNA test, you just swab the cheeks of your dog, ship it to the lab and receive a comprehensive report of the percentages of all the breeds found in your beloved friend. Beyond that, you’ll also get a breakdown of genetic health concerns for your dog’s specific breed mix and specific details about what diseases to be wary of.
The DNA My Dog Breed Identification Test is on sale for $59, down 25% from the regular cost of $79.
https://nypost.com/2019/10/16/unlock-your-dogs-genetic-secrets-with-these-dna-test-kits-on-sale/

After Failed Pancreatic Cancer Trial, Lilly to Continue Studies in Lung, Renal Cancer

Eli Lilly and Company announced that its Phase III SEQUOIA trial of pegilodecakin plus FOLOFX (folinic acid, 5-FU, oxaliplatin) in metastastic pancreatic cancer that had progressed during or after first-line gemcitabine-containing regimen did not meet its primary endpoint.
The SEQUOIA trial compared pegilodecakin and FOLFOX to FOLFOX alone. The primary endpoint was overall survival. The trial is a global, multi-center, randomized Phase III study. Key secondary endpoints are progression-free survival and objective response rate.
Lilly picked up pegilodecakin, an immunotherapy that stimulates the body’s immune system and expands tumor-attacking T-cells, when it acquired ARMO BioSciences in June 2018 for $1.6 billion. Pegilodecakin, a PEGylated IL-10, had shown clinical benefit as a monotherapy and in combination with chemotherapy and checkpoint inhibitors in several tumor types.
“Pancreatic cancer has proven to be one of the most difficult tumor types to treat and there have been very few recent treatment advancements in the later-line metastatic setting,” said Maura Dickler, vice president, late phase development, Lilly Oncology. “We are grateful to the patients, investigators and researchers who participated in the study. While we are disappointed by the outcome of the SEQUOIA study, we look forward to the upcoming results in lung cancer, learning from those results and increasing our understanding of pegilodecakin’s novel mechanism of action in cancer immunotherapy.”
The company is also conducting two Phase II trials, CYPRESS 1 and CYPRESS 2, of the drug in combination with checkpoint inhibitors in non-small cell lung cancer (NSCLC). The CYPRESS studies were launched by ARMO in March 2018, with results expected in early 2020. Lilly also indicates it is evaluating biomarkers and running studies in NSCLC and other cancers, including renal cell carcinoma, where pegilodecakin has shown promising activity.
Pancreatic cancer is a very difficult cancer to treat. Only about 3% of patients in the U.S. who are diagnosed live five years. It is the third leading cause of cancer death in the U.S. and barring more successful drug development, is expected to grow to the second leading cause of cancer-related death in the next decade. Worldwide, it is the seventh leading cause of cancer-related death.
Not many details about the trial were released, but Lilly did say the most common Grade 3/4 adverse events that occurred more than 5% were neutropenia, thrombocytopenia, fatigue and anemia. The company expects to present data at a future medical conference.
To be fair to Lilly, this was a particularly difficult clinical trial goal, with the patient population already not responding to gemcitabine-containing chemotherapy and looking for improvements in overall survival. The company is not giving up on the drug, with some analysts thinking that lung cancer in particular could be the biggest opportunity.
Earlier this week, Lilly announced it was closing its Erl Wood research center in Surrey, UK, which focuses on neuroscience research. The facility will close by the end of 2020, affecting 270 staffers with about 80 redundancies. About a third of the staff will move to a nearby location, but the company’s neuroscience research will move to the U.S.
At the beginning of the year, on January 8, Lilly announced it was cutting 250 jobs at its factory near Strasbourg in Eastern France. About 1,400 people worked at the site.
https://www.biospace.com/article/lilly-s-pancreatic-drug-flunks-phase-iii-trial/