Senior clerics in Iran said the Strait of Hormuz is not open to negotiation and warned against engaging with the United States.
“The Persian Gulf and the Strait of Hormuz are no longer negotiable,” Mohammad Javad Haj Ali Akbari said on Friday, adding a new legal framework would be pursued with Oman.
“Negotiating with America means surrender,” Mashhad Friday Prayer Imam Ahmad Alamolhoda said, adding Iran could leverage control of Hormuz without talks.
Iran’s economy is undergoing one of the most brutal stress tests in its modern history. Official annual inflation has surged to 50% according to central bank figures released shortly after the ceasefire, while the year-on-year rate reached as high as 67% through mid-April, according to the Wall Street Journal. The rial has crashed to a record low of 1.8 million to the dollar, roughly two million workers have lost their jobs, and the US naval blockade of the Strait of Hormuz continues to throttle the country’s oil exports and critical imports. Reconstruction costs from bombed infrastructure are estimated near $270 billion - alarmingly close to the country’s entire annual GDP of roughly $341 billion last year. What was already a sanctions-battered, mismanaged economy now confronts a grinding “no war, no peace” stalemate. Tehran is wagering that it can hunker down and endure a protracted war - allowing it to outlast American pressure. The early data and on-the-ground reality suggest that wager is being tested to its limits.
The human impact is immediate and visible in everyday Tehran life. A 56-year-old housewife described to Najmeh Bozorgmehr of the Financial Times how a simple block of cheese rose from 5.2 million rials to 6.7 million rials (about $5.09) in a single week. Comparable jumps have struck rice, eggs, chicken, red meat, and other staples. A popular Peugeot 207 has climbed from 18 billion rials to 25 billion since the conflict began, while officials are preparing to authorize a 40 percent increase in government-mandated cement prices.
The cost of living has soared, with the annual inflation rate reaching 67% in the month through mid-April from the same period a year earlier, according to Iran’s central bank. The subsidized price of red meat, which was mostly imported through sea routes, has gone up to the equivalent of around $3.60 a pound, beyond the reach of most in a country where the minimum wage is around $130 a month. -WSJ
Business consultant Siamak Ghassemi publicly advised Iranians that anything short of a near-doubling of wages would fail to offset the cost-of-living explosion. One small petrochemical-dependent factory outside the capital has already dismissed nearly a third of its workforce. A clothing business owner reported recent costs running 150 percent above sales, bluntly concluding, “This is not sustainable.”
Macro indicators reveal the depth of the damage. The Journal’s reporting, informed by Iranian officials and international analysts, estimates around one million direct job losses and another million indirect - equivalent to roughly 8 percent of the pre-war employed population of 25 million. War-related unemployment benefit applications have already reached 191,000. Steel output has dropped by up to 30 percent, while damaged petrochemical, gas, and steel complexes - major employers - grapple with raw-material shortages and physical destruction. Oil exports, which averaged 1.85 million barrels per day as recently as March, have been reduced to a near standstill, with shipping analysts at Kpler finding no confirmed evidence of cargoes successfully breaching the US blockade to reach buyers in China or elsewhere.
At the strategic core of the crisis lies the Strait of Hormuz. Iran initially tried to use the waterway as leverage by disrupting traffic; the US responded with a naval blockade that has effectively severed the Islamic Republic’s economic lifeline. Before the war, the strait carried the vast majority of Iran’s oil revenue and imports ranging from food and medicine to industrial components. In response, Tehran has activated emergency bypass routes: rail and road connections through Turkey, Armenia, and Azerbaijan, Caspian Sea ports supplied by Russia, Kazakhstan, and Turkmenistan, and new transit corridors via Pakistan. It has drawn heavily on strategic food reserves, raised the minimum wage, increased government salaries, issued monthly food coupons worth around $7 per person, and appealed to citizens to conserve energy and reduce driving.
Yet these measures are widely viewed as temporary holding operations rather than solutions. Virginia Tech economist Djavad Salehi-Isfahani told the Journal that Iranian leaders recognize ending the war is merely the prelude to an even harder challenge: managing a disillusioned and impoverished population without the rapid return of oil income. Middle East Institute fellow Alex Vatanka points out that while the regime can still portray endurance as a badge of national pride, prolonged revenue collapse increases the risk of renewed street mobilization. Vienna-based economist Mahdi Ghodsi offered a stark assessment: “Living is not affordable anymore. Iran is at its weakest point.”
One medium-sized steel entrepreneur told FT that his firm has so far avoided layoffs by shifting entirely to overland routes, but he expressed deep concern about how long this uncertain limbo can continue. Pre-war protests, already triggered by economic distress and crushed with lethal force earlier this year, provide a sobering precedent. The regime retains a formidable toolkit - subsidies, repression, parallel trade networks, and a narrative of resistance - but whether these tools can withstand another year of 50-percent-plus inflation, double-digit unemployment, and eroding living standards is the central question. This is not a sudden collapse, but a brutal, extended test of endurance whose outcome will shape not only Iran’s economy but the broader regional balance of power.
by Olivia Gomm via The Epoch Times (emphasis ours),
Culture Minister Marc Miller says the federal government has the role of regulating content on the internet and that Canada is years behind other countries when it comes to regulating “online harms.”
Miller told reporters on Parliament Hill April 29 that when it comes to the regulation of online content and social media, that role is “assumed by the federal government, whether we’re talking about moratoriums or the proper regulation of egregious online harms.”
“That’s stuff that we’re, frankly, a couple years behind in regulating, as we see other jurisdictions like Australia, like Britain, like France taking action,” Miller said, as was first covered by Blacklock’s Reporter. “We need to take action as well.”
Asked to comment on when the government plans on tabling a new online harms bill, Miller said “we’re working on it” and declined to share a timeline.
Miller told reporters earlier this month that a new online harms legislation is in the works and the government is “seriously” thinking about adding a social media ban for children to the bill, but did not provide a status or timeline for the introduction of the legislation then either.
The upcoming legislation will be the government’s third attempt to legislate on “online harms,” following previous proposals in 2021 and 2024, neither of which passed before Parliament was dissolved. Conservatives and civil liberties advocates had criticized both bills as posing a risk to freedom of expression.
In March, the federal government reconvened the same group of experts first formed in 2022 that made recommendations to the government on how to address online content deemed to be harmful, which led to Bill C-63.
The department of industry said in a recent report to the Senate social affairs committee that Ottawa is examining a “future online safety regime” meant to reduce content deemed as being harmful, such as hateful content and cyberbullying on large platforms.
“To advise on this proposal, the government has recently reconvened the Expert Advisory Group on Online Safety whose members previously contributed to the development of online harms legislation, to engage on new and emerging issues related to online harms,” the department said.
“Any future legislative proposal would be subject to parliamentary scrutiny, and details will be made public at the appropriate time.”
In 2021, Bill C-36 proposed a regulatory framework for harmful online content, but faced criticism from the opposition over its scope, including concerns about definitions of harmful speech and the extent of proposed oversight powers.
In 2024, Bill C-63 placed a stronger focus on protecting children and addressing specific categories of harmful content, and proposed the creation of new regulatory bodies such as a digital safety commissioner and ombudsperson. It also included amendments to the Criminal Code and human rights law, with stricter penalties for certain hate-related offences.
After pushback on the 2024 bill, the government said it was open to splitting the bill in two to facilitate the passage of measures protecting children, but the bill lapsed after Parliament was prorogued in January of last year.
Justice Minister Sean Fraser said last November that new legislation regulating online content would be different from the government’s previous proposals. Meanwhile, former Heritage Minister Steven Guilbeault said a few months earlier that upcoming online harms legislation would be similar to the versions tabled in 2024 and 2021.
The Liberals’ election platform last spring promised to “introduce legislation to protect children from horrific crimes including online sexploitation and extortion and give law enforcement and prosecutors the tools to stop these crimes and bring perpetrators to justice.”
The Liberals also pledged to “make it a criminal offence to distribute non-consensual sexual deepfakes” and to “increase penalties for the distribution of intimate images without consent.”
Jennifer Cowan, Noé Charter, and Paul Rowan Brian contributed to this report.
The scale of intervention was probably around ¥5.4 trillion, based on a comparison of Bank of Japan accounts released Friday and money broker forecasts. In 2024, authorities spent an average of ¥3.8 trillion on four occasions to support the yen.
Axsome Therapeutics' Auvelity has become the first non-antipsychotic therapy for agitation in patients with Alzheimer's disease to be approved by the FDA, which called the drug a "significant advancement" in care.
Auvelity (dextromethorphan/bupropion) – a first-in-class oral NMDA receptor antagonist and sigma-1 receptor agonist – is already approved to treat major depressive disorder (MDD) and made more than $500 million in sales last year.
The new indication is expected to lead to an acceleration in growth, as more than 7 million people are living with Alzheimer's in the US, and agitation – which can include verbal and physical aggression – is a very common symptom that affects an estimated 50% to 70% of all patients.
Antipsychotic medications are currently the main therapy for Alzheimer's agitation, but carry serious risks, including an increased risk of death, due to side effects. They also offer only modest, short-term benefits and may also accelerate cognitive decline, so are typically used as a last resort; for example, when there is a risk of harm to the patient or those around them.
While many antipsychotics are used off-label, the only FDA-approved option is Otsuka/Lundbeck's dopamine- and serotonin-targeting Rexulti (brexpiprazole), which got a green light for this use in 2023.
Auvelity is thought to target pathways involved in mood regulation and stress responses in the brain. In the ADVANCE-1 trial, it outperformed placebo in improving agitation scores over five weeks' follow-up, while in ACCORD-2 patients who switched from Auvelity to placebo had a shorter time to relapse than those who continued treatment with the drug.
According to geriatric psychiatry expert George Grossberg of Saint Louis School of Medicine in the US, Auvelity is the only FDA-approved product to show a statistically significant increase in time to relapse of agitation symptoms, compared to placebo, in a long-term study.
"Agitation in patients with dementia due to Alzheimer's disease is distressful, consequential, and challenging for patients, their caregivers and healthcare providers," he said, adding that Auvelity also showed "a compelling safety and tolerability profile, with rates of discontinuation due to adverse events that were low and matched those of placebo."
That profile should give Auvelity an immediate edge over Rexulti, which carries a boxed warning that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Analysts have said that Alzheimer's agitation could be a $1.5 billion market for Auvelity, on top of its potential in MDD, which has been estimated at between $1 billion and $3 billion at peak. Axsome, meanwhile, is hoping to extend the label for Auvelity even further, with a phase 2/3 clinical trial already running in smoking cessation.
Shares in the company rose nearly 13% on the news, driving its market cap to almost $10.7 billion.
https://pharmaphorum.com/news/axsome-breaks-new-ground-alzheimers-auvelity-ok
In its first meeting for months, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted against AstraZeneca's oral selective oestrogen receptor degrader (SERD) drug camizestrant.
By a margin of six votes to three, the panel concluded that the results of the SERENA-6 trial of camizestrant did not support use of camizestrant in combination with CDK inhibitors – Pfizer's Ibrance (palbociclib), Novartis' Kisqali (ribociclib), or Eli Lilly's Verzenios (abemaciclib) – as a first-line treatment for HR-positive, HER2-negative breast cancer with ESR1 mutations.
AZ had proposed a biomarker-based approach to treatment that involved measuring circulating tumour DNA (ctDNA) to detect ESR1 mutations – which point to the emergence of resistance to treatment – and switching patients from their current therapy to its oral SERD.
According to SERENA-6 data reported at last year's ASCO congress, that approach reduced the risk of disease progression or death by 56% compared to the CDK 4/6 inhibitors given in combination with an aromatase inhibitor. Mutations in ESR1 are the most common mechanism of acquired resistance to that treatment regimen.
The sticking point for panellists appeared to be that the improvement in progression-free survival (PFS) was not accompanied by a statistically significant gain in overall survival (OS), which is considered a more rigorous outcome measure. Some panellists suggested that an OS benefit should be seen before approval, given that AZ is proposing a step-change in established clinical practice for these patients.
That view was also laid out in the FDA review document (PDF), which suggested that there is not sufficient evidence from SERENA-6 to show the clinical benefit from a strategy in which patients receive camizestrant at ESR1 mutation detection, rather than at radiographic progression as at present.
"We are disappointed with the mixed outcome of today's ODAC meeting," said Susan Galbraith, AZ's head of oncology and haematology R&D.
"We strongly believe in the results of the SERENA-6 trial, and are encouraged that the committee saw camizestrant as a safe and effective potential new medicine," she added. "We remain confident in the clinical benefit the combination can bring to patients by changing therapeutic strategy at the earliest opportunity."
The company may have an opportunity to make its case when additional results from SERENA-6 are presented at this year's ASCO congress, which will start later this month in Chicago. Meanwhile, regulatory applications for camizestrant in this setting are also under review in the EU, Japan, and several other countries.
The FDA does not have to abide by the advice of the ODAC, but the vote suggests the ongoing SERENA-4 clinical trial of camizestrant in an all-comer HR-positive breast cancer population, with and without ESR1 mutations, is likely to be crucial for AZ as it tries to position the SERD as a new first-line treatment option for the disease – and build towards peak sales it has modelled at $5 billion a year. SERENA-4 data is due to read out in the latter half of this year.
There are currently two marketed drugs in the oral SERD class – Menarini/Stemline's Orserdu (elacestrant) and Eli Lilly's Inluriyo (imlunestrant) – which are both approved for second-line treatment of HR+, HER- breast cancer with ESR1 mutations.
Truqap backed for prostate cancer
The ODAC delivered better news for AZ with a seven-to-one vote in favour of its AKT inhibitor Truqap (capivasertib) in combination with Johnson & Johnson's Zytiga (abiraterone) and androgen deprivation therapy (ADT) for PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC).
This form of prostate cancer is known to be aggressive, progressing quickly to more advanced disease, and has limited treatment options. Estimates for the frequency of PTEN mutations in prostate cancer vary widely, between around 15% and 60%, depending on the type and stage of the disease, but testing for the biomarker isn't widespread at the moment.
Truqap is already approved for relapsed or refractory HR+/HER2- advanced breast cancer, but AZ's efforts to expand its use into other indications like triple-negative breast cancer have so far been unsuccessful.
The mHSPC filing is based on the results of the CAPItello-281 study, which showed that Truqap achieved a statistically significant 19% reduction in the risk of radiographic disease progression or death compared to placebo.
https://pharmaphorum.com/news/fdas-odac-delivers-one-loss-one-win-astrazeneca
The United Kingdom's Royal Navy said on Friday that ship traffic through the Strait of Hormuz has dropped by 90% since the war in Iran began on February 28.
The Navy noted that the UK Maritime Trade Operations (UKMTO) reported 41 incidents in regional waters, particularly in the Strait of Hormuz, with vessels attacked, damaged, or forced to turn back.
"The most distressing calls are those from ships under attack," UKMTO Head of Operations Commander Jo Black commented. "It's an absolutely terrifying experience for them – they're civilians, they're not prepared for this – drones, missiles, small arms fire aimed at their bridge or engine room, and threats to their safety – so they're stressed," he added.
https://breakingthenews.net/Article/UK-Navy:-Hormuz-traffic-dropped-by-90/66200372
