Court sides with EU on decision to revoke Ocaliva's license

 Advanz Pharma's bid to keep its Ocaliva treatment for rare liver disease primary biliary cholangitis (PBC) on the EU market has ended in failure.

The European Commission revoked the conditional marketing authorisation for Ocaliva (obeticholic acid) earlier this year on the grounds that its benefits no longer outweighed its risks as a treatment for PBC, a rare and progressive autoimmune disease – mainly affecting women – that results from the destruction of the bile ducts in the liver.

Advanz won a temporary reprieve in September after the General Court of the European Union ordered a suspension of the EC's decision, allowing the FXR agonist to remain on sale, but the company confirmed this morning that the court had decided not to extend the suspension any further.

The new order means that Ocaliva can no longer be made available to PBC patients in EU member states, as well as EEA countries (Iceland, Liechtenstein, and Norway), with immediate effect.

That leaves patients with limited second-line options for treatment if they fail to respond to or cannot tolerate ursodeoxycholic acid (UDCA), the standard first-line therapy, according to the European Association for the Study of the Liver (EASL), which has been lobbying for Ocaliva to remain available for patients who cannot tolerate or do not respond to UDCA treatment.

Until very recently, there were no second-line options for patients with PBC other than Ocaliva in the EU, although, that changed in September when Ipsen's PPAR agonist Iqirvo was approved by the Commission in combination with UDCA in adults who don't respond to UDCA alone, and as a monotherapy for those who can't tolerate the drug.

Another potential option is Gilead Sciences PPAR agonist Livdelzi (seladelpar), which was filed in the EU earlier this year by Gilead's subsidiary CymaBay Therapeutics and is under review by the EMA. 

In a statement, Advanz's chief executive, Steffen Wagner, took issue with the court's new ruling, saying that it only gauged whether there were "serious" and "irreparable" or "irreversible" damages to the company by the EC decision, and did not assess the impact on patients or the validity of the Commission's interpretation.

"Ocaliva is a much-needed treatment option for thousands of patients with PBC in Europe," he remarked. 

"As an FXR agonist, [it] has a different mechanism of action from other treatments and is backed by a wealth of positive real-world evidence, gathered from more than seven years of clinical use. Without Ocaliva, patients could be at increased risk of disease progression, including serious liver harm, liver transplantation, or death."

The only option open for existing patients seeking continued access to Ocaliva now is to get it via a compassionate-use or named-patient programme, and Advanz said it is looking into how this avenue may be kept open.

Meanwhile, Ocaliva is also facing difficulty on the other side of the Atlantic, with the FDA declining to grant full approval to the drug in PBN earlier this month. It will however continue to be available to patients under its accelerated approval status, which was granted in 2016, according to Intercept Pharma, which holds US rights.

https://pharmaphorum.com/news/court-sides-eu-decision-revoke-ocalivas-license

Study finds AZ's benralizumab a 'game-changer' in asthma

 Researchers in the UK say that AstraZeneca's benralizumab can have a dramatic impact if used to treat acute asthma attacks, calling it the first major advance for this aspect of the disease in 50 years.

The IL-5 inhibitor is already available under the Fasenra brand name for maintenance use in severe eosinophilic asthma, but a new study conducted by researchers at King's College London (KCL) suggests it could be a "game changer" if used routinely to treat acute attacks as they occur.

Nearly four million patients with asthma or chronic obstructive pulmonary disease (COPD) die each year, mostly from severe acute exacerbations that are currently treated with corticosteroids like prednisolone.

Around 50% of asthma attacks and 30% of COPD attacks are "eosinophilic exacerbations" – which means they should respond to IL-5 inhibitors like Fasenra that specifically target this type of inflammation.

In the investigator-led phase 2 ABRA trial, published in The Lancet Respiratory Medicine – researchers led by KCL's Professor Mona Bafadhel enrolled 158 patients presenting with acute asthma or COPD exacerbations associated with high levels of eosinophils in the blood.

They compared a higher dose of benralizumab than is currently approved in Fasenra (a 100mg subcutaneous injection plus the current standard therapy of 30mg prednisolone orally over five days) to the same prednisolone and benralizumab dosing regimens given with placebo.

The group taking prednisolone alone had a 74% treatment failure rate at 30 days, reducing to 45% in a pooled group of patients who received benralizumab, either with placebo or in combination with the steroid. Treatment failure was defined as a composite of death, admission to hospital, and any need for re-treatment requiring systemic glucocorticoids or antibiotics.

The time to first treatment failure event within 90 days was also significantly longer in the benralizumab group, according to the paper. After 28 days, respiratory symptoms like cough, wheezing, and breathlessness were found to be less common in the group that received the antibody, and patients also reported improved quality-of-life scores with the drug.

Bafadhel said the findings are potentially revolutionary, considering there are around two million asthma and COPD attacks in the UK alone each year.

"Benralizumab is a safe and effective drug already used to manage severe asthma," she said. "We've used the drug in a different way – at the point of an exacerbation – to show that it's more effective than steroid tablets, which is the only treatment currently available."

AZ provided benralizumab and funding for the ABRA study, but was not directly involved in the research. The researchers now hope to start a larger, phase 3 trial next year to try to generate further evidence of benralizumab's benefit in treating acute exacerbations.

Last year, KCL researchers also published the results of another trial called SHAMAL that showed benralizumab could allow people with asthma to reduce or even stop their use of inhaled steroids.

https://pharmaphorum.com/news/study-finds-azs-benralizumab-game-changer-asthma

Vietnam PM Aims for About 8% Economic Growth in 2025

Vietnam’s Prime Minister Pham Minh Chinh said the government will strive for economic growth of about 8% next year, significantly higher than the parliament’s goal for 2025.

While the National Assembly set a gross domestic product growth target of 6.5%-7% for next year, Chinh said the government sees 2025 as “the year of acceleration” and will strive for about 8% growth, according to a statement on the government’s website. It will prioritize promoting economic growth while controlling inflation and ensuring the budget deficit and public debt are within reasonable limits, the statement said.

Chinh forecasts 2024 GDP growth at above 7%, more than the government’s official target of 6.5% expansion, with inflation of less than 4%, according to the statement. The government forecasts the value of total imports and exports of goods and services to reach $807.7 billion this year, a record high.

Next year will create momentum for double-digit growth levels in the 2026-2030 period, according to the statement. The country will also strive to complete big infrastructure projects, including a 3,000 kilometer expressway and “basic” completion of Long Thanh International Airport’s initial phase, it said.

The government earlier said it will “drastically” push for 7% growth in 2024 and vowed to speed up the disbursement of public investment, which is far behind the year’s target. Spending for the first ten months of 2024 stood at just 52.29% of this year’s planned investment, according to a separate government statement on Friday. Chinh previously said that this is due to a combination of factors, including a lack of coordination among government agencies, and officials being afraid to take responsibility for their actions.

https://www.yahoo.com/news/vietnam-pm-aims-8-economic-020522841.html

Carrageenan Food Additive Associated With Increased Insulin Resistance

 by George Citroner via The Epoch Times (emphasis ours),

A new study suggests potential health risks associated with carrageenan (derived from red seaweed), a common food additive used as a thickener and found in everything from ice cream to plant-based milk.

Hanna Lepisto/Shutterstock

Researchers found that overweight people who ate foods with the additive became more insulin resistant and had more inflammation.

“In overweight participants, carrageenan exposure resulted in lower whole body and hepatic insulin sensitivity,” the study authors wrote, highlighting the need for further investigation into food additives that consumers might consider harmless.

Carrageenan Linked to Reduced Insulin Sensitivity, Inflammation

The research, published in BMC Medicine on Tuesday, was a randomized, double-blind, placebo-controlled trial involving 20 young, healthy male participants who received either 250 milligrams of carrageenan or a placebo twice daily over two weeks.

Key outcomes of the study included the measurement of insulin sensitivity through various tests, including the oral glucose tolerance test. Although no significant differences in overall insulin sensitivity were observed among all participants, interactions between participants’ body mass index (BMI) and their exposure to carrageenan or the placebo were notable.

In overweight people, carrageenan led to lower insulin sensitivity, increased brain inflammation, and higher levels of inflammatory markers (C-reactive protein and interleukin-6).

Additionally, carrageenan was linked to increased intestinal permeability, suggesting the participants’ digestive systems might allow substances to enter the bloodstream more easily. The study also showed immune cell activation and increased pro-inflammatory proteins released from white blood cells after carrageenan exposure. This supports the theory that the additive may influence insulin sensitivity by fostering inflammation.

While existing research demonstrates carrageenan’s correlation with heightened metabolic risks, inflammation, and gut disruption, the precise molecular mechanisms driving these adverse effects remain unclear.

While previous animal studies had suggested that carrageenan could induce glucose intolerance and worsen the adverse effects of high-fat diets, the new study represents one of the first clinical investigations into the additive’s effects on human glycemic response.

The researchers called for further research into the long-term health impacts of carrageenan and similar food additives, particularly in populations at higher risk for developing Type 2 diabetes.

Cutting Out Carrageenan

Carrageenan is fairly common in highly processed foods, dairy products such as chocolate milk and ice cream, and plant milks, Stephanie Schiff, a registered dietician and certified diabetes care and education specialist at Huntingdon Hospital, a part of Northwell Health in New York, told The Epoch Times.

The additive can be easily avoided if you’re eating a diet based on whole foods that are as close to their natural state as possible, she noted.

“If a food is made in a factory and has ingredients that are not familiar or are difficult to pronounce, it is likely highly processed and may contain carrageenan,” Schiff said. “If you’re eating a packaged good that is creamy or thick, check the label; it may contain carrageenan.” Although carrageenan is approved by the U.S. Food and Drug Administration (FDA), Schiff noted that it has no nutritional value.

Schiff also recommended a whole-food, plant-focused diet to circumvent carrageenan and other unhealthy additives. Alternatives such as gellan, locust bean, guar, and xanthan gums can be used in place of carrageenan without the associated health risks. However, she cautioned that buying organic does not guarantee a product is free from carrageenan.

The amount of carrageenan in a typical Western diet can range from 250 milligrams to 2 to 4 grams per person per day. Carrageenan is the fourth-most commonly consumed food additive in pediatric patients with Crohn’s disease, according to research.

The U.S. Department of Agriculture (USDA) currently allows carrageenan in organic food, despite opposition from the National Organic Standards Board (NOSB), a federal advisory board that makes recommendations on organic food and products.

Carrageenan Isn’t the Only Additive of Concern

According to Schiff, people should be aware of other additives commonly found in processed foods, including:

• Sodium Nitrite: Found in processed meats, nitrites have been linked to a higher risk of several types of cancer when heated.
• High-Fructose Corn Syrup: This sweetener is associated with weight gain, diabetes, and inflammation.
• Trans Fats: Present in hydrogenated and partially hydrogenated oils, these fats can increase the risk of heart disease, stroke, and diabetes.
• Monosodium Glutamate (MSG): MSG can cause sweating, flushing, numbness, palpitations, and tingling in sensitive individuals.

https://www.zerohedge.com/medical/study-finds-plant-based-food-additive-associated-increased-insulin-resistance

Zelenskiy urges Biden to rally support for Ukraine's NATO membership

 Ukrainian President Volodymyr Zelenskiy called on the outgoing U.S. administration of President Joe Biden on Sunday to help convince NATO members to invite Ukraine to join the alliance, as Ukraine's war with Russia enters an unpredictable new phase.

Kyiv wants NATO members to issue an invitation at an alliance meeting in Brussels this week as the invasion grinds toward its three-year mark and Russia makes battlefield gains.

Zelenskiy spoke to reporters in Kyiv alongside the new president of the European Union's council of member states, Antonio Costa, who travelled to Ukraine on his first day in office to show support for Kyiv in its war with Russia.

The Ukrainian leader, who has been calibrating Ukraine's positions before Donald Trump succeeds Biden in January, acknowledged that some NATO allies were still wary of inviting Kyiv to join the alliance, which obliges all members to aid each other if attacked.

"There are two months left in the current administration in the United States," he said. "They have influence on those few European sceptics of our future (in NATO)."

Trump has criticised the scale of U.S. support for Ukraine and has promised to end the war quickly, without saying how.

Russia and Ukraine have both interpreted this as increasing the likelihood of peace talks, which are not known to have been held since the first months after Russia's full-scale invasion in 2022. Both foes have tried to improve their positions on the battlefield and among diplomatic allies.

RUSSIAN ADVANCE

Moscow's troops have been capturing village after village in Ukraine's east, part of a drive to seize the industrial Donbas region, while Russian airstrikes are targeting a hobbled Ukrainian energy grid as winter sets in.

In November, the Biden administration granted Ukraine permission to use Western weapons to strike further into Russian territory. Moscow responded by attacking Ukraine with a new intermediate-range ballistic missile and has threatened further strikes on government sites in Kyiv.

Kyiv has long demanded Moscow withdraw all troops from its territory, and said Ukraine must be granted guarantees for its security comparable to NATO membership to prevent Russia from attacking again. Moscow, which controls nearly a fifth of Ukrainian territory, demands recognition of its annexation of Ukrainian land and permanent neutrality for Ukraine.

In an interview last week, Zelenskiy floated the idea of his country being granted NATO membership even while Russia occupies some captured territory, a solution he said could end the "hot stage" of the war.

In his remarks on Sunday Zelenskiy clarified that any invitation to join the alliance must extend to all Ukrainian territory, even if the alliance's collective defence agreement might not operate in areas occupied by Russian forces.

"There can be no NATO invitation to (only) a part of Ukrainian territory," he said, saying an invitation extended only to parts of Ukraine would amount to recognising that other parts were no longer Ukrainian.

Costa, who visited Ukraine along with the new EU foreign policy chief and the bloc's head of enlargement on the day they all took office, said the EU had "stood with you since the very first day of this war of aggression, and you can count on us to continue to stand with you."

"These are not just words," added Costa, a Portuguese former prime minister who replaced Charles Michel as president of the European Council and chair of EU summits.

Costa said Ukraine's process of joining the EU was marked by "a sense of urgency" and the bloc could take steps to integrate Ukraine before its entry, such as coordinating mobile phone roaming rules and letting some goods into the single market.

"We cannot manage this process as business as usual because it is a geopolitical choice," he said.

https://www.yahoo.com/news/eus-top-foreign-policy-officials-075335502.html

Russia Removes General in Charge of Syrian Operations: Military Bloggers

 Russian war bloggers reported on Sunday that Moscow has dismissed Sergei Kisel, the general in charge of its forces in Syria, after insurgents swept into the city of Aleppo in the biggest challenge to President Bashar al-Assad in years.

Russia is a key Assad ally. The removal of Kisel, 53, was reported by the Rybar Telegram channel, which is close to the Russian defence ministry, and by the Voenny Osvedomitel (Military Informant) blog.

Reuters has requested comment from the Russian defence ministry. Since the start of the Ukraine war, Russia has made a number of military reshuffles that were not publicly announced.

Unconfirmed reports said Kisel was being replaced by Colonel General Alexander Chaiko.

The military blogs were scathing about the performance of Kisel, who previously commanded Russia's 1st Guards Tank Army in the Kharkiv region of Ukraine, where Moscow's forces were driven back in a lightning counter-attack by Ukrainian troops in late 2022.

"Apparently he was supposed to reveal his hidden talents in Syria, but something got in the way again," Voenny Osvedomitel wrote.

Rybar commented: "The approach needs to change. The Syrian sandbox has long been a place for laundering the reputations of unsuccessful generals who turned out to be incompetent in the zone of the special military operation" - Russia's term for the war in Ukraine.

Rybar speculated that Russia might even turn to Sergei Surovikin, a general who earned the nickname "General Armageddon" for his ruthlessness in Syria and was briefly in charge of the Ukrainian war effort. Surovikin was demoted last year, when unconfirmed reports said he had been investigated for possible complicity in a mutiny by Russia's Wagner mercenary group.

The insurgent advance in Syria was the first since March 2020 when Russia and Turkey, which supports the rebels, agreed to a ceasefire that led to the halting of military action in northwest Syria.

On Sunday, the Syrian army said it had recaptured several towns that had been overrun by rebels in recent days. The insurgents are a coalition of Turkish-backed mainstream secular armed groups, along with Hayat Tahrir al-Sham, an Islamist group that is the opposition's most formidable military force.

Aleppo had been held by the government since a 2016 victory there, one of the war's major turning points, when Russian-backed Syrian forces besieged and laid waste to rebel-held eastern areas of what had been the country's largest city.

https://www.usnews.com/news/world/articles/2024-12-01/russia-removes-general-in-charge-of-syrian-operations-military-bloggers-say

Trudeau promised Trump tougher border controls, says top Canada official

 Canadian Prime Minister Justin Trudeau promised President-elect Donald Trump that Canada would toughen controls over the long undefended joint border, a senior Canadian official said on Sunday.

Trudeau flew to Florida on Friday to have dinner with Trump, who has promised to slap tariffs on Canadian imports unless Ottawa prevents migrants and drugs from crossing the frontier.

Canada sends 75% of all goods and services exports to the United States and tariffs would badly hurt the economy.

Public Safety Minister Dominic LeBlanc, who sat at the head table with Trudeau and Trump, said the two men discussed additional security measures Canada would be introducing.

"We're going to look to procure, for example, additional drones, additional police helicopters, we're going to redeploy personnel ... we believe that the border is secure," he told the Canadian Broadcasting Corp.

"It's important, I think, to show Canadians and the Americans that we're stepping up in a visible and muscular way, and that's exactly what we're going to do," he added, promising more details in the days and weeks to come.

Canada, he said, would continue to make the case that tariffs would damage both nations, given how interconnected the two economies are.

"I'm confident that the Americans will understand that it's not in their interest ... to proceed in this way," he said, describing the dinner meeting as very warm and cordial.

Trump said on Saturday he discussed the border, trade and energy in a "very productive" meeting with Trudeau.

The friendly nature of the dinner contrasts with previous exchanges between the two men.

Trump called Trudeau "a far left lunatic" in 2022 for requiring truck drivers crossing the border to be vaccinated against COVID. In June 2018, Trump walked out of a G7 summit in Quebec and blasted Trudeau for being "very dishonest and weak."

At the end of the dinner, LeBlanc said, Trump walked Trudeau to his car and said, "Keep in touch. Call me anytime. Talk soon."

https://www.ksl.com/article/51201744/trudeau-promised-trump-tougher-border-controls-says-top-canada-official