IO Bio plans cancer vaccine filing despite trial miss

 IO Biotech's cancer vaccine Cylembio failed to hit the mark in a phase 3 melanoma trial – but the company hopes to file for approval regardless.

The company said that the study "narrowly missed" the primary endpoint of an improvement in progression-free survival (PFS) when Cylembio (imsapepimut and etimupepimut) was added to MSD's PD-1 inhibitor Keytruda (pembrolizumab) in previously untreated advanced melanoma patients.

Despite that, it plans to have discussions with the FDA in the coming months in the hope of proceeding with a marketing application before the end of the year. Investors seemed unimpressed with the idea, however, and shares in IO closed down 42% after the announcement.

Cylembio is an 'off-the-shelf' therapeutic cancer vaccine based on engineered peptides designed to invoke an immune response against melanoma cells. It is intended for use alongside checkpoint inhibitors like Keytruda, which remove a molecular brake on immune responses to tumours.

Topline results from the study showed what IO said is the longest median PFS observed in a phase 3 advanced melanoma trial, coming in at 19.4 months for the combination versus 11.0 months for Keytruda given as a monotherapy, despite missing statistical significance with a p-value of 0.056, with a trend towards improved overall survival (OS).

The New York biotech also pointed to what it said were impressive data in specific patient subgroups, such as a fivefold improvement in median PFS among melanoma patients with PD-L1-negative tumours. A post-hoc analysis of patients who were checkpoint inhibitor-naïve at enrolment also showed a PFS improvement from 19.4 months with Keytruda to 24.8 months, which just crossed the significance threshold (p=0.037).

"The magnitude and durability of clinical effect observed consistently across subgroups supports our confidence in Cylembio and its potential as a treatment for advanced melanoma patients," said Mai-Britt Zocca, IO's chief executive.

"We look forward to engaging with the FDA to determine a potential path to approval based on these data," she added. One issue facing the company could be the low number of US patients included in its phase 3 trial, at just 17 out of a total enrolment of more than 400, although most of the remainder were from Europe.

There are a lot of personalised cancer vaccines coming through the industry pipeline for melanoma, including mRNA-based candidates from Moderna (mRNA-4157/V940), BioNTech (BNT111), and Strand Therapeutics (STX-001), but IO's candidate has the advantage of being usable by all patients without the need for it to be customised to each patient. Another potential all-comer candidate is Scancell's SCIB1/SCIB1+, which recently performed well in a phase 2 trial.

Meanwhile, there is one vaccine-like product approved to treat melanoma in the US – Amgen's Imlygic (talimogene laherparepvec), although, that is an engineered oncolytic virus administered locally to melanomas that is designed to kill and break open the cancer cells, releasing material that can stimulate the immune system. First approved in 2015, Imlygic is a niche product and has never been a big earner, but it has shown dramatic benefits in some patients.

GlobalData has suggested that, if approved, Cylembio could make annual sales of around $495 million in 2031.

https://pharmaphorum.com/news/io-bio-plans-cancer-vaccine-filing-despite-trial-miss

Apple partners with FuturHealth on weight loss

 Apple has made it possible to bundle a weight-loss therapy programme into its Fitness+ subscription, thanks to a partnership with telehealth company FuturHealth.

The partnership means that Apple's fitness and wellness service will be made available to all members who enrol onto FuturHealth's prescription weight-loss programme, which revolves around prescriptions for GLP-1 agonist-based drugs like Novo Nordisk's Wegovy (semaglutide) and Eli Lilly's Zepbound (tirzepatide).

The move suggests that tech giants like Apple are starting to respond to the massive industry building around GLP-1 weight-loss therapies, which are being mainly paid for out-of-pocket in the US, and could serve as a model for parallel programmes involving other chronic, lifestyle-related disorders.

FuturHealth provides 'personalised' GLP-1 drug therapies alongside other weight-loss offerings like meal kits and lifestyle support and advice, mainly through a smartphone app, and has hundreds of thousands of users in the US backed by a network of thousands of healthcare professionals. It delivers compounded medication directly to customer homes through a partnership with Alto Pharmacy.

Now, its customers – who pay between $130 and $1,300 per month, depending on the level of service – will get a Fitness+ subscription at no additional cost. It marks the first time that Apple's $11-per-month service has been integrated with a weight-loss drug offering.

"Our top priority has always been to help people on a weight loss journey experience real, long-lasting results through holistic lifestyle changes and personalised support," said Luke Mahoney, co-founder and chief executive of FuturHealth.

"With this Fitness+ offer, users can tap into thousands of workouts and meditations – wherever and whenever they choose – at no extra cost," he added.

A recent report from health insurance data non-profit organisation FAIR Health suggested that more than 2% of adult Americans are using GLP-1 therapies for obesity or those who are overweight, approximately 5 million people. However, studies suggest that individuals who stop taking the drugs often experience a regain in appetite and weight, and it is becoming well recognised that the key to maintaining the benefit is better after-treatment support.

Recent guidance from UK reimbursement authority NICE called for regular check-ins and practical strategies to support with sustainable routines, social support, and accessing community help, and the Fitness+ programme – with its trainer-led physical training, yoga, Pilates, dance, cycling, treadmill, rowing, and guided meditations – falls into that category.

The announcement comes as compounded semaglutide faces mounting legal restrictions, after semaglutide and tirzepatide were both removed from the official FDA shortages list. Companies are attempting to get around restrictions under loopholes in the law that allow compounders to make GLP-1 drugs in small quantities for patients whose needs are not met by a standard formulation.

Novo Nordisk and Lilly are both pursuing legal actions attempting to close that loophole.

https://pharmaphorum.com/news/apple-partners-futurhealth-weight-loss

Novartis two for two as ianalumab scores again

 A mere 24 hours after Novartis' ianalumab hit the mark in two phase 3 trials in Sjogren's syndrome, the drug has delivered another win in primary immune thrombocytopenia (ITP), another autoimmune disorder.

In the VAYHIT2 trial, the anti-BLyS/BAFF antibody was compared to placebo, both given on top of Novartis' established ITP therapy Promacta (eltrombopag), which made more than $2.2 billion in sales last year. Subjects in the study had previously been treated with corticosteroids for ITP, in which the immune system mistakenly targets and destroys blood platelets.

The combination of ianalumab and Promacta significantly prolonged the time to treatment failure (TTF), the trial's primary endpoint, which gauges how long patients maintain safe platelet levels during and after the treatment period. There was also a significantly higher rate of sustained improvements in platelet count at six months, according to Novartis.

Many people living with ITP cycle through multiple therapies, unable to achieve long-term disease control, so there is a pressing need for new treatment options, the company added.

"While current treatments for ITP are generally effective in raising platelet counts, many patients require lifelong treatment to maintain safe levels, which can create a lasting treatment burden," said Adam Cuker, a haematologist at the University of Pennsylvania who is one of the VAYHIT2 investigators.

"The results from VAYHIT2 are encouraging, as they suggest that ianalumab may support longer periods of disease control and reduce the need for continuous treatment," he added.

Novartis acquired ianalumab when it bought MorphoSys for $2.9 billion last year, and the new data in ITP comes right after the drug showed efficacy in Sjögren's, a condition that affects millions of people worldwide and causes dryness in mucosal surfaces like the eyes and mouth, as well as organ damage and an increase in the risk of life-threatening cancers.

That was the time that a drug has been shown to address the underlying pathology of Sjögren's in phase 3 trials, and Novartis is now moving swiftly ahead with plans to file ianalumab for approval in Sjögren's as it continues to develop the antibody for ITP and other B cell-driven autoimmune diseases.

Along with a phase 3 trial of the drug as a first-line therapy for ITP, trials are also on the go in warm autoimmune haemolytic anaemia, with readouts from all those studies due next year.

The ITP data is due to be presented later this year, with a regulatory filing anticipated for 2027, after the readout of the first-line study (VAYHIT1).

https://pharmaphorum.com/news/novartis-two-two-ianalumab-scores-again

'Lilly-backed scheme aims to help UK improve obesity care'

 Tens of thousands of NHS patients living with obesity could get help to reduce their weight through a partnership between the UK government and pharma group Eli Lilly.

Up to £85 million ($114 million) is being made available by the government and drugmaker under the public-private partnership, which aims to deliver new models of care for obesity – helped by a competition in which NHS organisations from all four UK nations will be able to put forward projects for consideration.

Those found most compelling will get funding for pilot studies, to see if they should be delivered at scale across the health service. The hope is that they will make weight management care easier to provide, through "new routes like digital platforms, local community-based access, and pharmacies," according to the government.

That ties in with the recently published NHS 10-Year Plan, which revolves around shifting care from hospital to community, from analogue to digital, and from sickness to prevention.

"New ways of accessing support to tackle obesity, such as through pharmacies or with help from digital tools, could be transformational for people's quality of life, and for society – allowing individuals to more easily manage their weight and freeing them from ill-health that holds them back in daily life – while reducing the strain on our NHS," commented Science and Technology Secretary Peter Kyle.

Supporting people living with obesity and those who are overweight is estimated to cost the NHS around £11 billion directly every year, with a wider cost to society of £74 billion.

The UK government will contribute up to £50 million of new investment into the scheme, with Lilly contributing up to £35 million of grant funding. It is part of a commitment made by Lilly at the UK's international investment summit last October that could generate up to £279 million of investment.

Lilly said it has worked with the Department of Science, Innovation, and Technology (DSIT) and Innovate UK on the design and guidelines for the competition, encouraging submissions to "consider elements such as alignment with clinical standards, resource efficiency, accessibility, and scalability."

"At Lilly, we are deeply committed to addressing the complex health challenge of obesity, and we are pleased to collaborate with the UK government and NHS partners," said Prof Rachel Batterham, Lilly's head of international medical affairs.

"Together, we aim to build an evidence base that could transform health outcomes for people living with obesity," she added.

A central part of this programme will be finding new ways to deliver obesity care that are accessible to everyone who can benefit from them, regardless of their background, according to the partners.

https://pharmaphorum.com/news/lilly-backed-scheme-aims-help-uk-improve-obesity-care

Power Bill Crisis Sends Maryland Gov. Wes Moore's Approval Plummeting

 The Democratic Party is in trouble over their beloved Maryland Governor Westley Watende Omari Moore, who is being positioned for the party's 2028 presidential run, as his polling numbers crater amid a tsunami of mounting crises.

"Governing is hard. Just ask Governor Wes Moore — plummeting 14 points in a year, scraping a dismal 50% approval in deep-blue Maryland," Change Annapolis, a bipartisan group of taxpayers, wrote in a post on X. 

Change Annapolis continued, "Marylanders are tired of his presidential vanity tour, crushing tax hikes, and an energy crisis of his own making," adding, "He's polling worse than O'Malley and Glendening at this point in their terms." 

Gov. Moore and his team of leftist radicals are running Annapolis into the ground, fueling a series of crises: a fiscal disaster and massive deficit, crushing tax hikes (setting the stage for a continued resident exodus to GOP-led states), an open-door haven for criminal illegal aliens, crime-ridden streets across major metros, and, worst of all, what's now being formally acknowledged: a full-blown "manufactured" power crisis. 

This energy crisis, a direct byproduct of failed green policies (in combination with AI data centers), has ignited power bill hyperinflation, hammering both poor and wealthy households while financially crushing mom-and-pop businesses. 

The first sign of the Democratic Party's panic over Moore's sliding poll numbers was in June, after a network of dark-money-funded NGOs purchased ad space on local radio stations and launched a propaganda brainwashing campaign to quell the growing wave of dissent surfacing across the state. 

In recent weeks, Moore has played the blame game, telling constituents that power bill hyperinflation is the direct result of the regional grid operator, PJM. Yet it was Democrats in the state that championed failed globalist "green" policies that led to the premature retirement of reliable fossil fuel power generation for intermittent solar and wind, leaving the grid more fragile than ever. 

... and residents found out on Monday afternoon about just how fragile the grid has become with all that fossil fuel spare capacity taken offline after hours of blackout power threats across central Maryland. 

The Maryland Freedom Caucus described yesterday's blackout threat as "a direct result of radical, extremist energy policies from Maryland Democrats and Governor Wes Moore, which are driving reliable power plants toward closure and leaving our grid on the brink."

In recent weeks, the Trump administration threw Democrats in the state a massive political lifeline to prevent rolling blackouts by granting a 90-day emergency waiver allowing the H.A. Wagner power plant to exceed pollution limits during peak energy hours. 

The exploding power bill crisis in Maryland, in the era of AI data centers, should have never existed if responsible lawmakers in Annapolis hadn't enacted foolish energy policies that retired stable fossil fuel power generation over some alleged climate crisis.

The accountability monster has now been released in the state - and this has so far shown up in sliding poll numbers for Moore - that could get a whole lot worse if power bills continue marching higher.

We've got some bad news.

What a mess! And it will only get worse. 

https://www.zerohedge.com/commodities/maryland-governor-wes-moore-polling-data-plummets-amid-power-bill-hyperinflation

Macrons Secretly Hired Investigator To Dig Up Dirt On Candace Owens

 French President Emmanuel Macron and First Lady Brigitte Macron have been revealed to have hired a private investigation firm to research conservative commentator Candace Owens, according to a new report from the Financial Times. The investigation comes as the French presidential couple pursues a defamation lawsuit against Owens over repeated allegations across multiple platforms that Brigitte Macron was born male.

The cross-continental probe was conducted by New York-based firm Nardell & Co, which, according to the British business news outlet, attempted to uncover damaging information about Owens by scrutinizing her public statements and political connections. Investigators reportedly looked into whether the popular podcaster had any direct ties to Russian officials or business interests.

While the investigation failed to establish any direct Russian connections, researchers did document Owens' online interactions with Russian political theorist Alexander Dugin. The report noted that both figures have shared each other's content on social media platforms various times.

The 218-page lawsuit, filed in Delaware Superior Court last week, includes 22 separate counts against Owens, including defamation, false light invasion of privacy, and defamation by implication. The legal action centers on Owens' repeated allegations across multiple platforms that Brigitte Macron was born male.

Researchers also documented her connections to other prominent conservative figures, including conservative journalist Tucker Carlson and Reform UK leader Nigel Farage.

"When it comes to Brigitte Macron, abusing Emmanuel and then blaming it on Russia is an unfortunate and sinister pattern," Owens responded to the Financial Times report.

The Macrons' attorney Tom Clare has characterized the case as straightforward defamation, stating that Owens "both promoted and expanded on" what he called "discredited falsehoods originally presented by a self-proclaimed spiritual medium and so-called investigative journalist."

According to court documents, Owens has promoted these claims through social media posts and an eight-part YouTube series titled "Becoming Brigitte," which the Macrons' legal team argues has led to significant online harassment of the first lady.

Court filings indicate the Macrons' representatives made multiple requests for retractions before filing the lawsuit. The presidential couple said in a joint statement that legal action became "the only remaining avenue for remedy" after Owens allegedly continued to promote the claims.

Despite calls for retractions, Owens has stood firm in her position, declaring in a 2024 social media post that she would "stake my entire professional reputation on the fact that Brigitte Macron is in fact a man."

The U.S. lawsuit follows mixed results for the Macrons in French courts addressing similar allegations. In July, a Paris appeals court overturned lower court convictions against two French women who had made comparable claims about the first lady. The appellate court ruled that defendants Amandine Roy and Natacha Rey had acted in "good faith" despite making false claims, eliminating their financial liability for damages previously awarded to the Macrons.

https://www.zerohedge.com/political/macrons-secretly-hired-investigator-dig-dirt-candace-owens

Republicans Need to Avoid Voting to Expand Obamacare

 If Republicans in the House and Senate vote to extend Obamacare subsidies, this will break a promise they have made over the years to dial back that law that increased cost on American health care consumers. The so called “Affordable Care Act” (ACA) has proven not all that affordable over the years. Now is the time for a Republican controlled federal government to start the process of dialing back that law.

During the Covid panic, Congress passed the American Rescue Plan that expanded eligibility for Obamacare subsidies for people enrolled in health plans provided in the marketplace. Looking in the rear-view mirror, the laws passed during that crisis have proven problematic. The Coronavirus Aid, Relief, and Economic Security Act (CARES Act) had the support of almost all of Congress. The problem is that the legislation contained the Paycheck Protection Program that ended up paying people not to work resulting in more state power to shut down small businesses and enabling masking and vaccine mandates. Many of the small businesses shut down during the pandemic never recovered.

The American Rescue Plan (ARP) contained some similar unintended consequences. Before that plan, people at the 150% poverty level to contribute a percentage of household income and those making over 400% were deemed ineligible for marketplace premium subsidies. The ARP changed that and fully subsidized the benchmark plan for people earning up to 150% and allowed those over 400% for premium subsidies.

Fraud has become a real problem under these new guidelines. Brian Blaze wrote in the Paragon Health Institute Newsletter on June 18, 2025, “using the latest federal data, we conservatively estimate that there are 6.4 million ineligible enrollees in exchange coverage—a more than 25% increase from 2024. Fraud is heavily concentrated in federal exchange states, particularly those that have not expanded Medicaid.” Blaze estimates that the cost will hit $27 billion this year alone. The problem is weak eligibility verification and perverse incentives created by the enhanced subsidies. Continuing this program will burden the taxpayers with massive new federal debt.

The Covid era enhanced subsidies have grown the universe of people covered by over ten million and have cut premium payments by almost half. The initial goal was to get the U.S. through the Covid pandemic and were supposed to only last until 2022 but they were extended to the end of this year back during the (also misnamed) “Inflation Reduction Act (IRA). Republicans should allow these enhanced subsidies to expire mirroring the original plan for them to end back in 2022. If Republicans vote to extend them, the projected cost to the taxpayer is $383 billion over the next decade.

Republicans have repeatedly promised to end Obamacare. NBC News reported before the 2024 election that “House Speaker Mike Johnson took a dig at Obamacare at an event in Pennsylvania on Monday, telling a crowd there would be ‘massive’ health care changes in America if Donald Trump wins the election.” Speaker Johnson said at the event “health care reform’s going to be a big part of the agenda.” Extending the subsidies would break that campaign promise.

One of the first Executive Orders (EO) President Trump signed during his first administration was one to repeal Obamacare. President Trump’s EO read, “It is the policy of my Administration to seek the prompt repeal of the Patient Protection and Affordable Care Act (Public Law 111-148), as amended (the “Act”). In the meantime, pending such repeal, it is imperative for the executive branch to ensure that the law is being efficiently implemented, take all actions consistent with law to minimize the unwarranted economic and regulatory burdens of the Act, and prepare to afford the States more flexibility and control to create a more free and open healthcare market.” Republicans have never wavered in their push to restore market forces into health care and to target waste, fraud and abuse in the program.

With the pending expiration of enhanced subsidies, it is important that Republicans stand strong and do not vote to continue an expansion of Obamacare that imposes a massive cost on taxpayers while enabling fraud.

Brian Darling is former Counsel for Sen. Rand Paul (R-KY).

https://www.realclearhealth.com/articles/2025/08/11/republicans_need_to_avoid_voting_to_expand_obamacare_1128035.html