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Svilar expected to be back against Sassuolo on 7 November
Mile Svilar wants to return to Roma’s goal. The Giallorossi goalkeeper has begun the countdown to his return, even anticipating his recovery time: he could be available for Gian Piero Gasperini by e...
Bobby Pulido’s Grand Old Democratic Party
The tejano musician who fashions himself as an old-school politician is fighting to win back South Texas—one wedding or quinceñera at a time.
Dallas Cowboys vs. Philadelphia Eagles: How to watch Monday Night Football tonight, start time and where to stream
Are these NFL teams actually good? Plus, a gruesome NBA injury
The Pulse Newsletter 📣 | This is The Athletic’s daily sports newsletter. Sign up here to receive The Pulse directly in your inbox. Good morning! Score 50 points today. Coming up: 🏈 A wild Week 7 💔 Williams carted off 🎠 Coaching carousel in full swing There is still so, so much time left in the NFL season. But after another baffling batch of games yesterday, I could not resist simply looking at the division standings and cackling at our current reality. Are some of these teams actually good? Are the teams we thought were good actually just OK? Do we know anything? ...
Did Elizabeth Holmes and Billy Evans get paid for their documentary?
Nathan Fielder’s documentary turns a dispute over paying its subjects into a central source of tension. Here’s what we know about the proposed deal.
Olivia Colman, Alexander Skarsgård on 'Wicker' sex scenes, big themes
Colman and co-star Alexander Skarsgård sat down with The Envelope to discuss the unusual (and unusually bawdy) fable of a medieval fisherwoman and the man of her wishes.
Shake-ups and layoffs reveal a culture clash inside Netflix
Increasingly, tensions have flared between the L.A.-based executives dedicated to movies and TV shows and its engineers and technicians in Silicon Valley over how best to expand the business and promote content on Netflix.
A night in the life of a scare actor at Dark Harbor in Long Beach
October unleashes a wave of spooky seasonal work for local actors, but all that creeping and crawling isn't easy.
Bass and Raman skirmish over treatment of small business. The Valley is a battleground
L.A. mayoral candidates Bass and Raman skirmish over their support for small businesses. The San Fernando Valley is a battleground
Bass and Raman skirmish over treatment of small business. The Valley is a battleground
L.A. mayoral candidates Bass and Raman skirmish over their support for small businesses. The San Fernando Valley is a battleground
Need help deciding on the state ballot measures? Here are my recommendations
You haven’t voted yet because the state propositions are too bewildering? I’m with you.
News Analysis: Trump says he's trying to entice Russia to negotiate. It doesn't appear to be working
Trump's break from long-standing tradition in U.S.-Russia relations was real, but it should not have been entirely surprising.
Bass and Raman skirmish over treatment of small business. The Valley is a battleground
L.A. mayoral candidates Bass and Raman skirmish over their support for small businesses. The San Fernando Valley is a battleground
Health reports - The Daily Reporter
Hancock County Health Department inspects restaurants and public food establishments four times annually. The following inspections are based on information obtained from Retail Food Inspection reports and are routine inspections, unless otherwise noted. “R” denotes violations repeated from a previous inspection.
Analysis | Saddam’s Cheesecake Factory: Trump’s predecessors go after him in ways only they can
In today’s edition … Voters are changing their minds … You tell me about your first time voting … but first …
Women’s heart health gets a new playbook, starting in childhood
For the first time, four leading medical societies have banded together to create a shared framework for assessing and improving women’s heart health across the lifespan, starting in childhood.
Trump dangles rural health dollars to push states to change hospital laws
The Trump administration has hinged federal funding for states on whether they end or loosen powerful but controversial laws that regulate the construction of new hospitals.
Wichitan remembered as a champion of local business, Wichita State and North High
Longtime advertising executive Don Stephan impacted a lot of Wichita businesses through the years with his career.
Americans for Prosperity dropped its support for Martina White and other GOP lawmakers over their prevailing-wage vote
The right-leaning group has pulled its endorsements at a time when Republicans in swing districts may need all the help they can get.
A New Way to Think About Women’s Heart Health
"We now know that unique signals of cardiovascular risk in women can be identified years and decades before heart disease develops," writes preventive cardiologist and epidemiologist Sadiya S. Khan.
Sight & Sound\'s \'Joshua\' coming to movie theaters this weekend; here are showtimes
Following a yearslong tradition that puts Sight & Sound's theater productions on movie theater screens nationwide, "Joshua — Live!" will soon make its premiere.
Trump’s name was everywhere in earlier Louisiana elections. What about this time?
Both Republican and Democratic candidates in Louisiana seem to avoid mentioning the president.
Bipartisan bankruptcy bill will help struggling small businesses
It’s good for for creditors and landlords, too.
How to watch the Tennessee governor's forum, and who's attending
“This is the first time in eight years Tennessee voters will elect a new governor and it’s important the public hear from the major candidates.\
Vote now for The Thibodaux Regional Health System Athletes of the Week (Oct. 19-25)
It's time to vote for the next Houma Today/Daily Comet Athlete of the Week sponsored by Vote now for The Thibodaux Regional Health System.
Ecumenical Patriarch: Church and Medical Science are "partners" in serving life
Ecumenical Patriarch Bartholomew emphasized the importance of cooperation between the Church and medical science during his address at the Church of St. Theodore Tiron in Rome on Sunday, October 25, 2026, paying tribute to healthcare professionals for their service during the COVID-19 pandemic. The Ecumenical Patriarch presided over the Divine…
Business News: Audemars Piguet Unveils 'The Watch Keepers' - A Digital Platform Offering Certified Pre-Owned Watches
The Le Brassus watchmaker will facilitate sales and auctions of brand-certified timepieces on a digital platform launching in Switzerland and Europe, with plans for expansion to other markets, including the U.S.
‘Been a Problem for a Very, Very Long Time’ — Revisiting the Time Fox’s Pam Oliver Revealed the Health Battle That Impacts Her Sideline Reporting
NFL sideline reporter Pam Oliver has been a fixture in the business for more than 30 years, covering the league for Fox. At 65, she’s also one of the most experienced voices on the sidelines, most recently covering the San Francisco 49ers’ Week 7 matchup against the Atlanta Falcons.
Singer Chris Brown to be sentenced over bottle attack at a London nightclub
Grammy-winning singer Chris Brown is to be sentenced Monday over brawling at a London nightclub in 2003.
Getting health insurance from your job will be extra pricey for 2027
Workers might start feeling faint when they sign up for work-based health coverage for 2027. Premiums are expected to skyrocket for the fourth year in a ...
Will Apple's overhauled MacBook Pro finally offer 5G cellular support?
This week, Apple will be overhauling the MacBook Pro for the first time since 2021. OLED, touch support, and a...
How to Manage Symptoms of Heart Failure
(Feature Impact) Americans are facing a growing health challenge, with 1 in 4 adults at risk of heart failure, according to the Heart Failure Society of America. Additionally, approximately 6.7 million U.S. adults who are 20 years old or older are currently living with heart failure, and that number is projected to reach 8.7 million by 2030. googletag.cmd.push(function() { googletag.display('JGFI_Article_300x250'); }); Managing heart failure is a significant expense to the U.S. healthcare system, costing the nation approximately $40 billion in 2020 and expected to increase to approximately $142 billion a year by 2050.If you (or a loved one) are living with the condition, consider these tips to help manage it.Adhere to the Treatment and Follow-Up PlanOngoing outpatient care is important when managing heart failure. Understand the treatment plan provided by your healthcare team, make diet and lifestyle changes, take medications as directed and keep recommended follow-up appointments.Pay attention to changes in symptoms and communicate with your healthcare provider if treatment does not seem to be working as expected. If their conditions are left unmanaged, patients can experience a range of heart-failure-related symptoms such as shortness of breath, fatigue, buildup of fluid and more.Understand Challenges with Diuretic TreatmentDiuretics help the body remove excess fluid and are commonly used to treat swelling, or edema, associated with heart failure. Your provider may try different diuretics, sometimes referred to as “water pills,” to manage your heart failure symptoms. However, intravenous (IV) diuretic therapy may be required for some patients if symptoms continue.Ask About Treatment Options Before IV Care Is NeededFor some adults, a healthcare provider may consider recommending an at-home, non-oral diuretic option prior to escalating to IV therapy.For example, ENBUMYST™ (bumetanide nasal spray) is a prescription diuretic used in adults to treat edema associated with congestive heart failure. It’s administered as a nasal spray for short-term use to manage excess fluid with the goal of transitioning to oral diuretic therapy when appropriate.Talk with your healthcare provider to learn more and visit enbumyst.com. Read the full Prescribing Information and Patient Information.Photo courtesy of Shutterstock googletag.cmd.push(function() { googletag.display('JGFI_Article2_300x250'); }); Important Safety InformationWhat is ENBUMYST?ENBUMYST is a prescription medicine used in adults to treat swelling caused by excess fluid in the body (edema) from congestive heart failure, liver disease, and kidney disease.What is the most important information I should know about ENBUMYST?ENBUMYST is a diuretic that helps your body remove fluid. Losing too much fluid can cause dehydration, low blood volume, and increase the risk of blood clots. Blood abnormalities may include decreased salts (electrolytes), and increased nitrogen, glucose and uric acid. The risk of these abnormalities is higher in elderly people, those using higher doses, or those who do not get enough electrolytes by mouth.You should not use ENBUMYST if you have severe electrolyte loss. Tell your healthcare provider if you experience unusual thirst; dizziness or lightheadedness; weakness or tiredness; fast heart rate; dry mouth or tongue; sudden pain; redness or swelling in your joints; pain, swelling, redness, or warmth in your leg; shortness of breath or fast breathing; high blood sugar; dark urine; pale, tight, cool or clammy skin; muscle cramps; confusion.Do not use ENBUMYST if you have low or no urine production or are allergic to bumetanide or to any of the ingredients in ENBUMYST.Before using ENBUMYST, tell your healthcare provider if you have low electrolytes, are on a low-salt diet, have diarrhea, diabetes, nasal problems such as a runny or stuffy nose or polyps, a history of nasal injury or surgery, are or plan to become pregnant, are or plan to breastfeed.Tell your healthcare provider about all the medicines you take, including prescriptions, over-the-counter medicines, vitamins, and herbal supplements.ENBUMYST may cause serious side effects, such as worsening kidney function and ringing in the ears or hearing loss.The most common side effects of ENBUMYST include dehydration, headache, muscle cramps, dizziness, low blood pressure, nausea, and abnormal brain functioning with certain liver problems.These are not all the possible side effects of ENBUMYST. Talk to your healthcare provider for more information.Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.US-ENBU-2600110 googletag.cmd.push(function() { googletag.display('JGFI_Article3_300x250'); });
High school sports roundup for Oct. 23-24, 2026
Friday, Oct. 23 Football Meadowdale defeated Lynnwood 48-0 The Meadowdale Mavericks jumped out to a 41-0 halftime lead en route to a 48-0 shutout win over the Lynnwood Royals. The […]
LLMs Recommend Far More Care Than Doctors
Sometimes a serendipitous study is just what the doctor ordered, especially when you need evidence to support your case on AI alignment.
Bears vs. Seahawks odds: Opening lines for Week 8 matchup
The Chicago Bears and the Seattle Seahawks are both coming off prime-time Week 7 wins, and they’ll face each other under the lights in Week 8 on Monday Night Football. The (5-2) Bears knocked off the New England Patriots 30 to 24 on Thursday Night Football, while the (4-3) Seahawks just won 20 to 3 […]
What to Stream: ‘Minions & Monsters,’ Matthew Perry, Daddy Yankee and ‘The Gilded Age’
A docuseries about Matthew Perry and the latest “Minions” movie are some of the new television, films, music and games headed to a device near you. Also among the streaming offerings worth your time this week, as selected by The Associated Press’ entertainment journalists: Daddy Yankee's new album, the fourth season of “The Gilded Age”
J.K. Dobbins scores rushing TD in Week 7
Denver Broncos running back J.K. Dobbins rushed six times for 23 yards and a touchdown in Week 7
Jack White Mourns Brother Eddie Gillis, Longtime Manager of Third Man Pressing
"The world lost a beautiful soul today,” White wrote of his older brother.
Everything Evanston: Fall flavors ramp up spirit, business in Evanston coffee shops
Autumn in Evanston brings seasonal menus and seasonal rushes as coffee shops fill with fall customers. SAMI HELLER: With the weather beginning to fall below 60 degrees, it’s time to ‘fall’ into the season of spooky movies, light sweaters and pumpkin spice. The Daily went into Evanston to see what the season of color-changing foliage...
Holland Taylor says ‘Two and a Half Men’ ‘never paid me very well,’ even after 4 Emmy noms
Holland Taylor is looking back on her 12-season run on ‘Two and a Half Men,’ during which time, she claims she never got a raise: ‘I loved a lot about that show, but they were not full of courtesies.’
TWICE's Nayeon to make solo comeback with 'NA-sty' on Nov. 20
Na-yeon of K-pop girl group TWICE will release her new solo project, “NA-sty,” on Nov. 20, marking her first solo comeback in about two years and f...
Deshaun Watson does just enough to guide Browns past Titans
Deshaun Watson threw for over 300 yards for the first time since the 2020 season in Week 7 against the Titans.
What's fair game in politics?
Jim Lokay discusses the controversy over Vivek Ramaswamy's attack ad involving his opponent Amy Acton's estranged mother, plus how affordability arguments are shaping the last week of the midterm campaign with Andrew Donaldson of Ordinary Times.
IN GOOD HEALTH: Preparing for respiratory illness season
By Leanna Coy, FNP-BC As temperatures begin to cool and the holiday season gets underway with Halloween this month, it’s time to prepare for fall and winter respiratory illnesses. As we…
13 Practical Tools You Should Carry For Fall Camping
Autumn is a glorious time to get the max use out of your camping gear. These tools will supplement your summer kit for an enhanced fall experience.
Clemson at Florida State 2014: QB Jameis Winston Suspended
2014 Clemson at Florida State was an overtime thriller, with QB Jameis Winston reduced to a cheerleader.
Rams Return to Winning Ways With Statement Win Over Raiders
The Los Angeles Rams beat the Las Vegas Raiders, 35-21, on Sunday, winning a game for the first time since Week 4. The post Rams Return to Winning Ways With Statement Win Over Raiders appeared first on LA Sports Report.
Peyton Manning’s Role in Colts GM Search Clarified After Chris Ballard Firing
Peyton Manning is one of the greatest players, if not the greatest, to ever play for the Indianapolis Colts. The former quarterback is one of the most decorated players in American football history. He has won the Super Bowl two times, and is a five-time NFL Most Valuable Player. The Colts have not found the […] The post Peyton Manning’s Role in Colts GM Search Clarified After Chris Ballard Firing appeared first on Gridiron Heroics.
Attackers kill nurse, severely injure health worker responding to Ebola case in eastern Congo
The World Health Organization reports that a nurse has been killed and a health worker severely injured in an attack while responding to an Ebola alert in Congo.
Supercomputer reveals first two billion years of ‘cosmic web’
The Center for Astrophysics’s simulation offers the most detailed look yet at the infancy of the universe after the Big Bang
Tiny magnetic vortices could help computers work more like your brain
Scientists have filmed tiny magnetic vortices called skyrmions melting out of an organized lattice for the first time, revealing new ways to manipulate these unusual structures. The breakthrough could help make brain-like computers a reality, potentially enabling dramatically smaller and more energy-efficient technology.
Business is booming for Giacinta’s at the Bridge
BRIDGEPORT – Since welcoming Giacinta’s Gelato & Caffe to their new location in the multipurpose Bridge at Bridgeport Exempted Village School District, the place has been a go-to spot for students and community members looking for that morning pick-me-up. Owner Audrey Brahler made some time between morning rushes of buyers to talk about the success […]
How Obama and Trump Made their Cases in Dueling Midterm Speeches
At rallies this weekend, Mr. Obama and Mr. Trump delivered two starkly contrasting pitches, differing in style and substance.
Quinshon Judkins flirts with century mark in Week 7 return
Cleveland Browns running back Quinshon Judkins (ankle) rushed 17 times for 96 yards and two touchdowns in Week 7
Chiefs vs. Seahawks live updates, inactives, where to watch: Kenneth Walker III faces Seattle for first time since Super Bowl MVP run
9th Circuit panel questions basis for feds' request to block 20,000 California ballots
Two judges questioned the Justice Department's lawyer about how the Trump administration's position squared with the law.
Serbia’s Vucic concedes defeat in seismic political shift
The long-serving strongman leader of Serbia, Aleksandar Vucic, has conceded defeat in an election that pitted him and his right-wing party against a diverse student-led opposition movement that spent two years protesting his government
Cam Skattebo confirms injury after Giants beat Texans in overtime
Cam Skattebo confirmed he did suffer an injury on his 42-yard overtime run.
Everton’s five-game winning home run ended by Aston Villa
Everton’s five-match winning run at Goodison Park has come to an end with Aston Villa running out 3-2 winners on Merseyside this afternoon.Brian Sørensen enjoyed a successful return to his former c...
British Columbia's new premier lucks into the job in unexpected political turn
An electoral gamble by the Canadian province's outgoing premier, David Eby, backfired as the provincial Conservatives take power for the first time since 1928.
BC's new premier lucked into the job in an unexpected political turn
An electoral gamble by the Canadian province's outgoing premier, David Eby, backfired as the provincial Conservatives take power for the first time since 1928.
Ravens surrender 35 unanswered points in stunning loss to Bengals
Baltimore squandered a 13-0 halftime lead as Joe Burrow threw four touchdown passes and Cincinnati handed the Ravens a 35-13 defeat
Sharpen memory and fight brain fog with simple 60-second trick from a neurologist
Dr. Rhonda Voskuhl explains why crosswords and sudoku miss the mark for brain fog and which timed word games actually target verbal memory loss.
Germaphobe primates want to avoid getting sick, too
Some monkeys become significantly more cautious about food sources that appear contaminated after experiencing deadly outbreaks of disease.
Big Las Vegas show closures mark a transitional time for Strip entertainment
The culture of Las Vegas is inextricably linked to the artists and technicians behind the Strip’s vibrant live entertainment industry, so any time a show closes
Kaine, Randall tour county's new Crisis Receiving and Stabilization Center
The Loudoun County Crisis Receiving and Stabilization Center's first day of operations on Oct. 22 included a tour by Sen. Tim Kaine, D-Va., and county Board of Supervisors Phyllis J.
Christian McCaffrey able to return to Week 7 game
49ers RB Christian McCaffrey returns to Week 7 game after missing time with thigh issue
How to watch the 2026 WNBA Finals: Golden State Valkyries vs. Atlanta Dream Game 5 time, schedule, where to stream and more
Trump’s Election Attacks Enter New Pre-emptive Phase
A lawsuit by the Justice Department challenging a potential narrow loss by the GOP Senate incumbent in Alaska reflects a new tactic by the president to try to shape the election results.
‘I love spending time with them’: Lewis Hamilton opens up about Kim Kardashian’s kids
Lewis Hamilton and Kim Kardashian have been one of the most talked-about couples in sports and entertainment this year, but the seven-time Formula 1 world champion has rarely said much about the relat...
Phantom Blade Zero Preload Time & Date Revealed; Clocks in at 145 GB as PC Requirements Listed
While a lot of PS5 gamers are eagerly awaiting Phantom Blade Zero, some might not know that the game is also releasing day and date on PC. If you're one…
The Times' top 25 high school football rankings
A look at the top 25 high school football teams in the Southland after Week 9.
Uganda tightens Ebola border controls and requires returnees from Congo to pay for quarantine
Uganda is reinforcing existing border controls requiring citizens returning from Congo to undergo 21 days of quarantine at their own expense, the Health Ministry said Sunday, as investigators examine how a woman who traveled from Uganda to Nigeria contracted Ebola.
Chris Olave targeted 10 times in Week 7
New Orleans wide receiver Chris Olave went for six receptions for 56 yards on 10 targets in Week 7
My husband and I moved abroad in our 50s, didn't want to waste time
Leslie Hodgin and her husband decided to stop waiting to move abroad, selling most of their belongings and relocating to the Netherlands.
‘You Can See Everything’ surges with $19.5M at box office; ‘Clayface’ takes No. 1
DC Studios scored a modest, R-rated win with “Clayface,” landing a $24 million opening weekend, according to studio estimates Sunday.
Senate rivals seek support from Alaska Native voters
The major candidates in Alaska’s U.S. Senate race are both casting themselves as strong voices on Alaska Native issues as they seek support from the key constituency ahead of the Nov. 3 election
The Making Of: Addams Family Values, Ocean Software's Attempt to Mix Hollywood & the Legend of Zelda
"Management didn't really understand development or the creative process"
Jaylen Warren surpasses 100-yard mark in Week 7
Steelers RB Jaylen Warren rushes for at least 100 yards for third time this season
Clayface Takes First Place While Holmes Documentary Grows in Week Two
Clayface opened with $24.5M, while A24's three-hour Elizabeth Holmes documentary You Can See Everything grew 25% in its second weekend.
Warriors honor Bay Area sports reporter Michael Wagaman
After Michael Wagaman passed away in early August, Dallas Braden took time to tribute him during his call of the Athletics’ game on NBC Sports Bay Area and California. Wagaman had covered Bay Area sports teams since 1996, including for the Associated Press, and freelanced for NBC Sports Bay Area and California at the time…
Lakers 1st-Round Draft Pick Floated as Trade Piece
The Los Angeles Lakers are off to a fast start. Could it be time to weigh trading away some young pieces to boost the rotation? The post Lakers 1st-Round Draft Pick Floated as Trade Piece appeared first on HEAVY.
Kansas at Duke: Exhibition OGT
Kansas basketball hopes to follow the football team with a win today. Yeah, this game doesn’t count, but any time you’re playing Duke you want to win. Plus, this exhibition game is a big enough deal that ESPN is broadcasting it live (probably because they know everyone else will be watching football. I’m probably going […]
Bloomington business continues to blossom
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In West Maui, Democrat-turned-Republican defends House seat against Lahaina Strong organizer, local business advocate
Incumbent Rep. Elle Cochran, Green Party candidate Pā’ele Kiakona and Democratic nominee Sne Patel are battling to represent West Maui at a pivotal time in the fire recovery.
Browns Week 7 inactives: Who's in, who's out?
The Browns are the healthiest they have been in some time as they take on the Titans in Week 7.
Game Time Thread: Juventus vs. Lecce
MATCH INFO When: Sunday, Oct. 25, 2026. Where: Stadio Via del Mare, Lecce, Italy. Official kickoff time: 6 p.m. local time in Italy and across Europe, 8 p.m. in the United Kingdom, 1 p.m. Eastern time, 12 p.m. Central time, 10 a.m. Pacific time. (Please note that the fall time change in Italy goes into effect on Sunday, […]
ESMO: Roche touts ‘convincing’ phase 3 KRAS data after win over rivals
Roche has shed more light on its investigational KRAS G12C inhibitor's phase 3 victory over Amgen’s Lumakras and Bristol Myers Squibb’s Krazati. The open-label Krascendo 1 trial enrolled 338 people with previously treated KRAS G12C-mutated non-small cell lung cancer (NSCLC). Patients who had already received a KRAS G12C inhibitor or pan-KRAS/RAS inhibitor were excluded from the trial. Participants received either divarasib once daily, Lumakras once daily or Krazati twice daily. Roche announced back in July that divarasib had demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS), meeting the trial’s primary and key secondary endpoints. But the Swiss pharma had been holding back the detailed data until now. At the European Society for Medical Oncology (ESMO) Congress in Madrid, Roche revealed that median OS for the 167 patients who received divarasib was 17.7 months, compared to 12 months for the 171 patients who received Lumakras or Krazati. The benefit was similarly clear when it came to median PFS, which stood at 9.8 months versus 5.7 months, respectively. A total of 44% of patients receiving divarasib were alive without disease progression at one year, compared to 24% of the control group, according to Roche’s presentation. It was a similar story for the objective response rate, which came in at 58% for divarasib versus 32% for the control group, while median duration of response was 11.9 months versus 6.9 months. Stefan Frings, M.D., Ph.D., deputy chief medical officer at Roche Pharma, told Fierce that the data made for a “very comprehensive, strong package, which should be convincing to health authorities.” “It’s an important advance for patients with lung cancer,” Frings said in an interview at a Madrid hotel during the conference. “It's a second-line setting, and patients who receive divarasib benefit compared to the current first-generation KRAS G12C inhibitors by having far longer overall survival,” he continued. “They live longer. They have better progression-free survival, better response rates, and with a safety profile which is—if [anything]—even better,” he said. According to Roche, 4.8% of patients receiving divarasib discontinued treatment due to treatment-related adverse events, compared to 11.7% in the control group. Serious treatment-related adverse events were also less common with divarasib, at 7.8% versus 15.2%. Roche’s confidence in divarasib had been building even before this phase 3 success. The candidate had already shown better potency and selectivity than the incumbent KRAS G12C inhibitors Krazati and Lumakras in preclinical tests. After cross-trial comparisons suggested that the edge translated into better clinical outcomes, Roche axed a study comparing divarasib to the chemotherapy docetaxel and went toe-to-toe with Lumakras and Krazati. “We designed the drug on purpose with higher potency and better selectivity,” Frings explained. “So, based on preclinical models, we clearly knew it would be superior to the first generation.” “It’s honestly not so frequent that pharma companies go head-to-head,” he added. “But if you want to make a point, if you want to convince payers, prescribers and patients … then a head-to-head win is rather rewarding.” While Amgen and BMS reached the regulatory finish line first for KRAS G12C-mutated, locally advanced or metastatic NSCLC in 2021 and 2022, respectively, they have struggled to capitalize on their head start. Krazati brought in $55 million for BMS in the second quarter, while Lumakras delivered $111 million to Amgen. For its part, Roche is aiming for peak divarasib sales of 1 billion to 2 billion Swiss francs ($1.2 billion to $2.5 billion), according to Frings. The Big Pharma is currently recruiting patients into a phase 3 trial comparing divarasib plus Keytruda against Keytruda plus chemotherapy in previously untreated advanced or metastatic nonsquamous KRAS G12C-mutated NSCLC. Roche has previously suggested that sales in metastatic disease would account for most of the forecast. Frings was tight-lipped on the exact timeline for a regulatory filing but said the Swiss pharma is “certainly keen to get this to as many patients as possible around the world.” Roche has more RAS drugs coming up behind divarasib. The pharma has already launched phase 1 trials of a pan-RAS inhibitor called RG6505 and a KRAS G12D inhibitor dubbed RG6620 in solid tumors. Roche’s partner Chugai Pharmaceutical is also testing a pan-KRAS inhibitor called AUBE00. Roche has made a “deliberate effort” to test a range of RAS drugs, Frings said. “If you have many rare mutations and you are scrambling to find sufficient patients, a pan-RAS inhibitor makes a lot of sense,” he explained.
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Preview
The Men's First Team are back in Serie A action, this time heading south to face Lecce in Puglia.The Serie A Matchday 8 clash is set to take place at the Stadio Via del Mare at 18:00 CET on Sunday, Oc...
LETTER TO THE EDITOR: Misleading political mailer is a smear campaign
The recent misleading smear mailer by the opponents of Denise Krause in the Oregon Senate campaign is the most disgusting exhibit of money and indecency used to capture uninformed voters’ […]