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Sunday, June 9, 2019

PG&E Shuts Power to California Resort Area to Prevent Wildfires

PG&E Corp. turned off power to more than 17,000 customers in Northern California this weekend as part of the first wave of what the utility has said will likely be numerous pre-emptive shutdowns this year to help prevent deadly wildfires.
It came after the National Weather Service issued its first red-flag warning, which signals high fire danger, of 2019 for a region that has until now been mostly cool and moist.
About 1,600 businesses and homes in parts of Napa, Yolo and Solano counties, located about 75 miles northeast of San Francisco lost power from 6 a.m. Saturday morning until late that night.
Also Saturday night, PG&E shut off power to an additional 16,000 customers in Butte and Yuba counties, including the town of Paradise, which was destroyed by the Camp Fire last year. That blackout was still ongoing Sunday.
Paradise resident Robert Broome, who weathered the Camp Fire inside his home after unsuccessfully trying to evacuate, said Saturday night’s outage was inconvenient but better than another deadly blaze. “It’s what they should have done last time and they didn’t,” the online radio host said Sunday from his house, where the power went out at about 9 p.m. the previous evening.
The San Francisco-based company earlier this year announced its plan to become the first utility in the U.S. to intentionally shut off power to help prevent its transmission equipment from igniting a fire. PG&E owns and operates thousands of miles of power lines that snake through tinder-dry forests and brush and has said its equipment likely sparked the 153,000-acre Camp Fire last November, killing 85 people. California officials have since verified PG&E’s culpability.
State records show PG&E equipment has caused hundreds of other fires in recent years. The company filed for bankruptcy protection in January to protect itself from wildfire-related liability.
PG&E warned Friday afternoon that the Napa County resort town of Lake Berryessa might be among the areas to face blackouts this weekend. Nonetheless, Saturday morning’s shutdown came as an unpleasant wake-up call to the boat shops and other businesses that cater to crowds of people visiting the 16-mile-long reservoir perched in a rugged mountain.
“This is better than having a fire, but it definitely makes it difficult, ” Josh Grimstad, manager of Lake Berryessa Boat & Jet Ski Rentals, said that morning in a dark office with no working phones and a long line of customers.
An office assistant retrieved reservations from a desktop computer powered by a portable generator too weak to provide energy to much else. Most customers took the inconvenience in stride, although 45-year-old Gabriel Garcia grumbled that PG&E was doing too little too late.
“Now they’re taking all these precautions,” said Mr. Garcia, a carpenter from Napa who was renting a WaveRunner boat to ride with his 8-year-old son. “They didn’t before all of these fires.”
Other people praised PG&E for taking precautionary steps.
“If we can get adjusted to these outages, it’s worth it, because these fires just kill business,” said Mike Medina, co-owner of the 55-site Spanish Flat Campground along Lake Berryessa.
Mr. Medina and two partners struggled Saturday to load about a dozen empty gasoline containers onto a pickup truck so they could get fuel to keep a generator running. The campground needs power in part to keep 200 bags of ice worth about $1,000 from melting, they said.
PG&E previously warned that in such shutdowns, electricity wouldn’t be restored for at least 24 hours and possibly days longer until crews can inspect power lines for any damage.
“We understand people without power is an inconvenience, but we are doing this for the safety of the communities,” said Paul Moreno, a spokesman for the utility.
The Turtle Rock Bar & Cafe — a popular biker haunt with dollar bills festooning to the ceiling — sat just outside the blackout area. Owner Pete Leung said he invested in a $20,000 generator last December, believing that power outages would become more commonplace in the region. Two years ago, the business barely escaped the flames of a wildfire, which left a trail of dead trees on all sides.
“They’re going to cut your power now, that’s the new norm,” Mr. Leung said.
His home atop a nearby ridge did have its electricity turned off on Saturday, prompting Mr. Leung to do what more residents are doing: fire up an emergency generator. But with the 8,000-watt generator consuming five gallons of gasoline every eight hours, he said it could get expensive if the shutdown lasts too long.
“They don’t tell you when they’re going to turn the power back on, and that’s the hard part,” Mr. Leung, 42, said Saturday afternoon as he tossed a ball in his backyard for his Labrador retriever, Sammy.

Tandem Diabetes Care Reports Positive Results of 2 Insulin Pump Studies

Significant Time-in-Range Improvements Demonstrated in Adult and Pediatric Age Groups
Tandem Diabetes Care, Inc. (TNDM), a leading insulin delivery and diabetes technology company, today announced positive results from two studies of the t:slim X2™ insulin pump with Control-IQ™ advanced hybrid closed-loop technology. Data from both studies demonstrated that the system achieved the primary outcome of increasing time in range (70-180 mg/dL) without any severe hypoglycemic events. The t:slim X2 insulin pump with Control-IQ technology utilizes Dexcom G6 continuous glucose monitoring (CGM) sensor values to predict glucose levels and adjust insulin delivery to prevent highs and lows, while still allowing the user to manually bolus for meals. The system also automates correction boluses, which is a feature not commercially available today on automated insulin delivery devices.

MannKind Presents Positive Afrezza Data of 3 Studies at American Diabetes Assn

MannKind Corporation (Nasdaq: MNKD) announced that new data from three different studies of Afrezza® (insulin human) Inhalation Powder were released at the American Diabetes Association’s 79th Scientific Sessions, being held June 7-11, in San Francisco, California.
Poster 1350-P:   Safety and Pharmacokinetics of Technosphere Insulin in Pediatric Patients
MannKind will present a poster with initial information from its ongoing study of Safety and Pharmacokinetics of Technosphere Insulin (Afrezza) in Pediatric Patients ¹ on Monday, June 10.  This study is the first step in preparation for a phase 3 safety and efficacy study.
Poster Highlights:                         
  • In pediatric patients, the rapid rise in insulin concentrations corresponded with early postprandial glucose control within the first hour post-dose. The profile is similar to that previously observed in adults.
  • Consistent with its safety profile in adults, Afrezza was generally well-tolerated in pediatric patients; most treatment emergent adverse events were of mild severity, and no severe hypoglycemia was observed.
  • These data will help guide the finalization of the protocol for a phase 3 safety and efficacy study.
“We are excited to share the progress of the ongoing pediatric study program,” said David Kendall, M.D., Chief Medical Officer of MannKind. “As is well known, type 1 diabetes is often diagnosed in children and adolescents, and these individuals will continue to require insulin therapy throughout their lives. Evaluating as quickly as possible the potential use of Afrezza in children and adolescents as an option for mealtime insulin therapy is a top priority for MannKind.”
Poster 136-LB:   Effective Treatment of T2D Patients Uncontrolled on Multiple Diabetes Medications by Adding Afrezza® Mealtime Ultra-Rapid Insulin
Dr. Philip Levin and colleagues presented data from an independent study supported and funded by MannKind. Dr. Levin presented late-breaking clinical data on interim results of a study² showing how a fixed titration schedule can be implemented to achieve better time in range and reduction of overall A1c.
Late Breaking Poster Highlights:
  • Enrolled adult patients with uncontrolled type 2 diabetes on two or more therapies (orals/ basal/ GLPs) – with the addition of Afrezza at all meals by means of a rapid and ongoing titration protocol
  • Observed a mean decrease in A1c of ~1.6% (all subjects with A1c reduction over 12 weeks of study)
  • 93% (13 of 14 subjects) achieved A1c below 8% (mean baseline A1c 9.1%)
  • Reduced hyperglycemia (>250mg/dL) by 74%
  • Increased time in range more than 75%; daily glucose decreased by ~50 mg/dL as measured by blinded continuous glucose monitoring
  • No significant difference in rates of hypoglycemia with the addition of Afrezza
“We are pleased to share the interim analysis from our independent investigator-initiated trial of Afrezza therapy. These preliminary data significantly advance our understanding of the potential clinical benefits and practical use of Afrezza therapy for those living with type 2 diabetes,” stated Philip Levin, M.D. of Bay West Endocrinology Associates and MODEL Clinical Research in Baltimore, MD. “Data generated to this point are encouraging and support the use of Afrezza as prandial therapy earlier in the treatment of type 2 diabetes.”
Oral Abstract 
151-OR: Technosphere Insulin Provides Better Early Postprandial Glucose Control than Subcutaneous Rapid-Acting Analog
MannKind investigators also shared data at an oral presentation³ using mixed meal tolerance testing to assess glucose control, Afrezza dosing and overall safety in a cohort of individuals with type 1 diabetes.
Oral Presentation Highlights:
  • When compared to rapid acting injected insulin, Afrezza provided significantly better glucose control in the first two hours following the meal.
  • Even when adjusting the dose of Afrezza using up to two times the dose of injected insulin aspart, Afrezza treatment was associated with lower rates of overall and level 2 hypoglycemia – an observation that was particularly evident in the late (>2 hour) post-meal period.

Single Course of Provention PRV-031 Delays Type 1 Diabetes Onset in High-Risk

Provention Bio, Inc. (Nasdaq:PRVB), a clinical stage biopharmaceutical company dedicated to intercepting and preventing immune-mediated disease, today announced that results from the National Institutes of Health (NIH)-sponsored “At-Risk” Study were published on-line in The New England Journal of Medicine and presented at the Scientific Sessions of the 79th Annual American Diabetes Association (ADA) meeting.  The “At-Risk” Study was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), with additional support from JDRF. The study was conducted by the Type 1 Diabetes TrialNet, an international collaboration aimed at discovering ways to delay or prevent type 1 diabetes (T1D), and evaluated Provention’s PRV-031 (teplizumab) for the prevention or delay of clinical T1D in relatives of type 1 diabetics at high-risk of developing the disease.  PRV-031 (teplizumab) is an anti-CD3 monoclonal antibody in development for the interception and prevention of clinical T1D.
The “At Risk” Study enrolled 76 participants ages 8 to 49 who were “At-Risk” because they had two or more T1D autoantibodies and abnormal glucose metabolism (dysglycemia); 72% of participants were under the age of 18.  Subjects were randomized to receive either PRV-031 (teplizumab) or placebo.
Results from the study showed that a single 14-day course of PRV-031 (teplizumab) significantly delayed the onset and diagnosis of clinical T1D, as compared to placebo, by a median of 2 years in children and adults considered to be at high risk. The median time to clinical diagnosis of T1D for placebo participants was just over 24 months.  In comparison, the median time for PRV-031 (teplizumab)-treated participants to clinical diagnosis of T1D was just over 48 months (p=0.006). During the trial, 72% in the placebo group developed clinical diabetes compared to only 43% of the PRV-031 (teplizumab) group. PRV-031 (teplizumab) was well tolerated and the safety data were consistent with prior studies in newly diagnosed patients.
“This groundbreaking study demonstrates that we can use immunotherapy, specifically PRV-031 (teplizumab), to prevent or significantly delay the onset of clinical type 1 diabetes by at least two years in individuals who will almost certainly progress to clinical disease,” said Dr. Eleanor Ramos, Provention’s Chief Medical Officer and Chief Operating Officer.  “More importantly, approximately 60% of subjects in the study did not develop T1D following only one course of PRV-031 therapy, double the placebo group. Teplizumab is the first immune modulator to show a delay in the clinical onset of type 1 diabetes.”
Dr. Kevan Herold, M.D., Professor of Immunobiology and Medicine at Yale University, lead author of the study, stated, “These results have real clinical meaning for individuals at-risk of developing clinical type 1 diabetes such as family members of patients. Delaying the onset of clinical T1D may mean the disease burden could be postponed to a point at which patients are better able to manage their disease such as after infancy, elementary school, high school or even college. With PRV-031 (teplizumab), we may now be able to intervene and fundamentally change the progression of T1D for these at-risk subjects. In addition, we look forward to learning more as we observe patients during the study’s follow-up period, which will also evaluate the long-term outcomes for those in whom the diagnosis of disease has been delayed to see if they will be diagnosed with T1D or are protected.”
Conference Call and Webcast Information
Provention Bio will discuss these results via conference call on Monday, June 10, 2019 at 8:30 AM ET. A webcast presentation will also be available on the Investors page of the Company’s website, www.proventionbio.com.  To access the call, please dial 1-877-870-4263 (domestic) or 1-412-317-0790 (international) five minutes prior to the start time and ask to be connected to the “Provention Bio Call”. A webcast replay of the call will be available beginning at 11:00 AM ET on the day of the call.

Health paradox: New US diabetes cases fall as obesity rises

The number of new diabetes cases among U.S. adults keeps falling, even as obesity rates climb, and health officials aren’t sure why.
New federal data released Tuesday found the number of new diabetes diagnoses fell to about 1.3 million in 2017, down from 1.7 million in 2009.
Earlier research had spotted a decline, and the new report shows it’s been going on for close to a decade. But health officials are not celebrating.
“The bottom line is we don’t know for sure what’s driving these trends,” said the lead author of the new report, Dr. Stephen Benoit of the Centers for Disease Control and Prevention. Among the possibilities: Changes in testing and getting people to improve their health before becoming diabetic.
The report was published by the journal BMJ Open Diabetes Research & Care. The statistics run through 2017. Last year’s numbers are not yet available, Benoit said.
Diabetes is a disease in which sugar builds up in the blood. The most common form is tied to obesity, and the number of diabetics ballooned as U.S. obesity rates increased.
But other factors also might have pushed up annual diabetes diagnoses from 2000 to 2010, and they may partly explain why the numbers have been going down since, some experts said.
First, the diagnostic threshold was lowered in the late 1990s. That caused more people to be counted as diabetics, but the impact of that may have played out.
“We might have mined out a lot of the previously unrecognized cases” and so new diagnoses in the last several years are more likely to be actual new illnesses, said Dr. John Buse, a University of North Carolina diabetes expert.
Meanwhile, doctors have increasingly used a newer blood test to diagnoses diabetes. It’s much easier than tests that required patients to fast for 12 hours or to undergo repeated blood draws over two hours.
The American Diabetes Association recommended the new test, known as the hemoglobin A1C blood test, for routine screening in 2010. Because it’s easier to do, it would be expected to lead to more diagnoses. But some experts say it may miss a large proportion of early cases in which people aren’t showing symptoms. “You may be missing people that would have been diagnosed” with older tests, Benoit said.
Another possibility: Increasingly, more doctors have been diagnosing “prediabetes,” a health condition in which blood sugar levels are high but not high enough to hit the diabetes threshold. Physicians typically push such patients into exercise programs and urge them to change their diet.
“Prediabetes is becoming a more accepted diagnosis” and may be causing an increasing number of patients to improve their health before becoming diabetic, said Dr. Tannaz Moin, a UCLA expert.
The new report is based on a large national survey conducted by the government every year. Participants were asked if they had been diagnosed with diabetes, and also if the diagnosis was made in the previous year.
It found the rate of new diabetes cases fell to 6 per 1,000 U.S. adults in 2017, from 9.2 per 1,000 in 2009. That’s a 35 percent drop, and marks the longest decline since the government started tracking the statistic nearly 40 years ago, according to the CDC.
The decrease was mainly seen among white adults, the researchers said.
Meanwhile, the overall estimate of how many Americans have diabetes — whether the diagnosis is recent or not — has been holding steady at 80 per 1,000 U.S. adults. That translates to about 21 million Americans.

‘Mix and Match’ Options Emerging in Automated Insulin Delivery

As automated insulin delivery is rapidly evolving, interchangeability between insulin pumps and sensors on the various platforms is emerging as a key component to moving the field forward.
Here at the American Diabetes Association (ADA) 2019 Scientific Sessions, many attendees who follow the technology were surprised by the announcement that Medtronic will be working with the nonprofit Tidepool to create an interoperable automated insulin pump system, a category the US Food and Drug Administration (FDA) now calls “alternate controller enabled (ACE)” pumps.
Currently, Medtronic manufactures the only commercially available hybrid closed-loop system (previously known as the artificial pancreas) and is the only company to manufacture both the insulin pump and continuous glucose monitor (CGM) components of such automated insulin delivery systems.
Tidepool is a data hub for patients and clinicians to combine and view data from insulin pumps, CGMs, and blood glucose meters. It also stores information about meals, exercise, and other daily events. As a next step, the organization is now developing the Tidepool Loop app, which would serve as a platform allowing interoperability between various diabetes devices.
“Pairing our future Bluetooth-enabled MiniMed ACE pump with Tidepool Loop would enable an FDA-approved interoperable system — with pump and CGM components — that may be mixed and matched with the Tidepool Loop app as the person with diabetes chooses,” Medtronic announced on June 6, the day before the conference.

It’s Tough Being First…

Here at the meeting, an oral abstract session on automated insulin delivery held on June 8 included a presentation from Stanford University on real-world clinical experience with Medtronic’s hybrid MiniMed 670G system in which — similar to a report at ENDO 2019: The Endocrine Society Annual Meeting in March — clinical experience with this first commercially available artificial pancreas has been less than ideal, with many patients abandoning the system and frequently citing difficulties with the sensor as the reason.
“It’s always tough being first, from the standpoint of the 670G, and this cooperation [with Tidepool] is going to give folks all sorts of other options,” Rayhan Lal, MD, of Stanford University, California, told Medscape Medical News. “Other companies are starting to collaborate, and I think to stay in the space you have to cooperate with others in the field,” he added.
Indeed, session moderator Alanna Weisman, MD, University of Toronto, Ontario, Canada, told Medscape Medical News, “Interchangeability is a big issue…I think patients would like to be able to mix and match and choose the devices that work best for them.”
Weisman said she was surprised by the Medtronic announcement, but that “it’s very exciting.”
Also presented during the same abstract session were new data on the third generation of Beta Bionics’ investigational iLet system, including its use with two different sensors — the Dexcom G5 and implantable Eversense(Senseonics).

Real-World Results Differ From Research

Lal presented data from a 1-year prospective observational study of 79 adult and pediatric patients (aged 9-61 years) who started using the 670G system at Stanford between May 2017 and May 2018. Most (72%) had previously used a Medtronic pump, 51% had previously used a Dexcom sensor, and 33% had previously used a Medtronic CGM.
The proportions discontinuing the “auto mode” function of the 670G rose over time, from just 1% at week 1 to 40% at 6 months to 46% at 1 year. Compared to those who continued using auto mode, those who discontinued were significantly younger (22.3 vs 31.5 years; P = .02) and had been using the Medtronic Guardian 3 sensor for less time prior to entering auto mode (P = .001).
Of note, although it wasn’t significant due to low numbers, participants who were using a Dexcom along with the 670G – and feeding the numbers from the Dexcom into the 670G system – were also more likely to discontinue auto mode (31% vs 13%; 8 vs 4 patients; P = 0.11).
“Sensor issues” accounted for 60% of the reasons listed for abandoning auto mode at 1 year, including need for multiple daily calibrations, sensor alerts, and systems automatically exiting auto mode and requiring additional fingersticks. Other cited reasons, such as problems obtaining supplies and fear of hypoglycemia, were less common (17% and 10%, respectively).
“Education and adequate preparation are crucial in setting realistic expectations for closed-loop systems. A focus on usability and human factors is necessary to ensure patients stay on treatment,” Lal concluded.
In separate press releases issued on June 8, Medtronic announced enrolment of the first study participants in a pivotal trial of its Bluetooth-enabled 780G advanced hybrid closed-loop system, designed to automate the delivery of correction boluses to address current or anticipated high blood glucose levels based on sensor readings, and a next-generation Guardian CGM, designed to improve accuracy and system performance and reduce the number of calibrations.

iLet Works With Different Sensors, Ultimately to Include Glucagon

Rabab Z. Jafri, MD, a pediatric endocrinologist at Massachusetts General Hospital, Boston, presented the iLet data, the first on safety and efficacy of the Gen3 iLet, “a purpose-built bionic pancreas platform” designed to administer both insulin and glucagon, although the current data are for use with insulin alone.
The iLet uses only body weight to initialize and uses autonomous machine learning to adapt to the individual user. Unlike other closed-loop systems, it doesn’t require the user to enter carbohydrate counts, basal rates, or correction factors. It responds to input from the Dexcom G5 or Eversense CGM.
In the current study, 34 adult outpatients were enrolled who had type 1 diabetes. A random-order cross-over was used to compare the insulin-only mode of the iLet to usual care for 7 days each. Mean CGM glucose values were 155 mg/dL while wearing the insulin-only iLet versus 162 mg/dL with usual care (P = .09). Time spent with blood glucose < 54 mg/dL didn’t differ significantly (P = .64), but iLet did improve time spent in the 70-180 mg/dL range compared with usual care (70% vs 62%; P = .01).
Results didn’t differ between the 17 patients using the Dexcom G5 and the 17 patients using the Eversense.
Findings from this study have led to improvements in the design of the Gen4 iLet, Jafri noted.
Separately on June 6, Beta Bionics and Zealand Pharma announced resultsfrom the first home-use study of the Gen3 bihormonal configuration of iLet, using Zealand’s stable aqueous glucagon analog dasiglucagon.
Ten adults with type 1 diabetes wore the bihormonal and insulin-only iLet configurations for 1 week each. During the bihormonal period, they achieved a mean CGM glucose level of 139 mg/dL on days 2-7 of use compared with 149 mg/dL during the insulin-only period (P < .01).
During the bihormonal period, participants spent 79% of the time with CGM glucose levels in the range of 70-180 mg/dL on days 2-7 of use compared with 71% during the insulin-only period (P < .01).

iLet Available Soon; Patients Want Choices

Principal investigator Steven Russell, MD, Massachusetts General Hospital, Boston, told Medscape Medical News that Beta Bionics plans to start a pivotal study with the Gen4 version — the one they hope to bring to market — next year.
The company anticipates that the insulin-only configuration could be commercially available within 2 years, while the bihormonal version will take longer since it will involve a new drug approval.
Weisman, who published a meta-analysis of closed-loop systems in 2017, told Medscape Medical News that although her data show the dual-hormone version of iLet has some benefits over the single-hormone version, they also add complexity, so “it’s a trade-off.”
That’s part of the decision-making clinicians will need to help patients within the very near future as these systems reach the market, she noted.
Regarding interchangeability of devices in these systems, Weisman observed: “Patients want choices. I think being able to combine systems to fit their needs makes sense.”
Jafri and Weisman have reported no relevant financial relationships. Lal has reported being a consultant for Abbott Diabetes Care and receives research funding from Medtronic. Russell has reported being on advisory panels for Companion Medical and Unomedical, is a consultant for Flexion Therapeutics, and receives research support from Beta Bionics, MITRE Corporation, Novo Nordisk, and Zealand Pharma. He also has other relationships with ADOCIA, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, and Senseonics.
ADA 2019 Scientific Sessions. Presented June 8, 2019. Abstract 80-OR

Sanofi Soliqua Phase 3 meets primary objective: American Diabetes Assn

Soliqua® Phase 3 results significantly lowered blood sugar levels compared to GLP-1 receptor agonist treatments
  • Patients switched to Soliqua reached an average blood sugar below the American Diabetes Association recommended level of 7%
  • Full Phase 3 data presented today at the American Diabetes Association (ADA) 79th Scientific Sessions

In a Phase 3 study[1] evaluating adults with type 2 diabetes inadequately controlled by GLP-1 receptor agonist (GLP-1 RA) treatments, Soliqua®/Suliqua®[2] (insulin glargine 100 Units/mL and lixisenatide) met the primary study objective by demonstrating a statistically superior reduction of average blood sugar level (HbA1c) after 26 weeks, compared with continuing GLP-1 RA treatment.
The LixiLan-G study included either a daily or once-weekly GLP-1 RA treatment as comparator. More patients who switched to Soliqua achieved HbA1c levels below 7%, a target recommended by the ADA, compared with those who stayed on previous GLP-1 RA therapy. More patients who switched to Soliqua also achieved the composite endpoint of HbA1c below 7% without documented symptomatic hypoglycemia (low blood sugar levels).
The study showed a safety profile consistent with the established profiles of the treatments studied: the most common classes of adverse event were gastrointestinal events (i.e., nausea, diarrhea and or vomiting) and hypoglycemia.
The full Phase 3 data results were presented today for the first time as an oral presentation at the 79th Scientific Sessions of the ADA in San Francisco.