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Wednesday, May 7, 2025

Trump's Middle East envoy Witkoff to brief U.N. Security Council

 U.S. President Donald Trump's Middle East envoy Steve Witkoff plans to brief members of the United Nations Security council on Wednesday, diplomats said.

The briefing, to which all 15 members of the Security Council have been invited, would take place at the U.S. mission to the United Nations, the sources said, speaking on condition of anonymity.

Axios, which first reported the news, said Witkoff is expected to brief on U.S. policy regarding the war in Gaza and nuclear talks with Iran. It said he was expected to focus primarily on Gaza and on a new aid mechanism proposed by Israel and the U.S.

Israel has so far given few details about the new mechanism. European leaders and aid groups have criticised Israel's plans to take over distribution of humanitarian aid in Gaza and use private companies to get food to families after two months in which the military has prevented supplies entering the Strip.

Israeli Prime Minister Benjamin Netanyahu said on Monday an expanded offensive against Palestinian militant group Hamas would be "intensive," after his security cabinet approved plans that may include seizing the Gaza Strip and controlling aid.

On Monday, Jan Egeland, secretary-general of the Norwegian Refugee Council, said on X that Israel was demanding that the U.N. and non-governmental organizations shut down their aid distribution system in Gaza.

https://www.yahoo.com/news/trumps-middle-east-envoy-witkoff-153448546.html

Stocks Slide As Apple Exec Admits Efforts To Replace Google For AI Search

 Apple Senior Vice President of Services Eddy Cue testified that the company is "actively exploring" a redesign of its Safari browser to prioritize AI-powered search engines, amid potential fallout from its deal with Google, according to Bloomberg.

Cue disclosed Wednesday while testifying in the U.S. Justice Department's antitrust lawsuit against Alphabet. The case centers on Apple and Google's estimated $20 billion-a-year agreement that designates Google as the default search engine in Apple's Safari browser.

Cue revealed that Safari search volumes declined for the first time in April, prompting the company to evaluate alternatives. He specifically mentioned Perplexity and Anthropic as potential options.

Here are the latest headlines: 

APPLE'S CUE: LOST SLEEP OVER POSSIBILITY OF LOSING REV. SHARE

  • APPLE'S CUE: BELIEVES PERPLEXITY, ANTHROPIC COULD BE OPTIONS

  • APPLE LOOKED AT ANTHROPIC, DEEPSEEK, GROK, PERPLEXITY FOR AI

This news sent Google shares sinking as much as 5%.

Apple shares fell to a session low of 1.7%. 

Sliding Apple and Google price action sent US main equity futures lower. 

*Developing...  

https://www.zerohedge.com/markets/stocks-slide-apple-exec-admits-efforts-replace-google-ai-search

A Scary Plastic Study Should Probably Be Recycled

 By Josh Bloom

Three hundred fifty thousand of you are predicted to die every year from heart disease caused by exposure to plastics, a new Lancet study says. But you can rest easy: the headlines don't match the threat. You are unlikely to be in a bag, plastic, or otherwise, anytime soon. Here's why.
#Perhaps overkill. Provided that Diet Pepsi isn't in the bottle. Then it's accu…

Lately, the press has feasted on a new Lancet article that concludes that about 350,000 of you are going to die yearly from heart disease brought about by long-term ingestion of di-2-ethylhexylphthalate (DEHP), a chemical used to soften plastics. The good news is that the study's data are hardly convincing. Why? We need to look at the good and the bad – the numbers behind the study and how they were used. 

The claim

The authors claim that in 2018 about 356,000 people, aged 55-64, died from heart disease caused by DEHP, one of many plastic-softening chemicals that belong to the class of organic chemicals called phthalates. This number represents about 13.5% of all heart disease deaths. If true, this is pretty bad. But is it? Don't go hurling your Tupperware out the window just yet.

DEHP (and other phthalate analogs) have long been poster children [1] of the anti-plastic/anti-chemical movements. Countless studies of phthalates, many of them junk, have been published, raising concerns that they can potentially interfere with hormones and affect metabolism (aka "endocrine disruptors"). The studies — mostly from the U.S. — have postulated links between phthalate exposure and conditions like obesity, diabetes, and heart disease. 

The idea behind this new study was to estimate whether DEHP might be contributing to cardiovascular deaths globally, and if so, and if so, how much — especially in light of efforts like the Global Plastics Treaty, which aims to curb plastic pollution and its health effects. Keep the word "estimate" in mind. 

For the study the researchers built a computer model and used available data on DEHP exposure levels –based on urinary metabolites– from biomonitoring studies conducted U.S., Canada, Europe, and parts of Asia and Africa, as well as published meta-analyses. Where no data existed, they estimated exposure levels using regional averages, looking for associations between average cardiovascular death rates in 55–64-year-olds and estimated DEHP exposures in the population

Does this study mean anything?

This depends on whether you consider a hazard ratio (HR) of 1.10 meaningful. In English, an HR of 1.10 means that there is only a 10% difference between two groups that are being compared, a very small difference by any measure. In this case It means that there was a 10% increased risk of cardiovascular death associated with higher DEHP levels. But even this number may be overstated (or possibly understated) depending on how well the retrospective study [2] used appropriate controls to rule out confounders – uncorrected variables that can impact the HR significantly. More on this below.

This figure wasn’t newly calculated. It came from an earlier U.S. study of about 5,300 people aged 55–64 in the NHANES [3] database, who had their urinary phthalate levels measured and were followed over time to track mortality. The global study then applied this same 10% risk estimate across nearly 1 billion people worldwide in that age group in 2018 — regardless of country, health system, lifestyle, or environmental conditions, and came up with the number.

Positives: A very large study population

The study’s strength lies in its massive scale. It pulled together mortality and chemical exposure data from around 200 countries, helping spotlight areas — especially South Asia and the Middle East — with disproportionately high estimated exposures. This type of global modeling is useful for setting public health priorities, particularly where local data is scarce. It looks for trends, but not as good looking for specific numbers.

Negatives: Confounders and questionable assumptions

The negatives appear to badly outweigh the positives, so is the study's estimate meaningless? No, it's not — but it’s very far from definitive either. here are a few issues:

  • The conclusion is built on a single modest sized (~5,000) U.S.-based study with a very low HR, and applied broadly using assumptions that may not hold across diverse populations.
  • For example, smoking is far more prevalent in Asia than in the US. This could result in the overstatement of the impact of DEHP in Asia because the excess deaths that are attributed to DEHP could arise from more tobacco use instead. This is probably the most important cofounder and probably the biggest weakness of the study.
  • There is no correction for the differences in public health and healthcare access in the US and other parts of the world. Much higher statin use in the US compared to other countries could result in an artificially high low CV death in here, but obesity and other metabolic diseases could push the numbers in the opposite direction.
  • Adding to the uncertainty, the model included a 10-year time lag between exposure and outcome — comparing DEHP levels from 2008 to cardiovascular deaths in 2018. This also introduces more room for error, since many other factors — like diet, pollution, smoking rates, and access to care — also changed during that time and weren’t accounted for.
  • DEHP exposure wasn’t measured directly. Instead, researchers used four urinary metabolites as proxies, introducing individual or group metabolism as another possible confounder.

Because the model doesn’t account for these differences across countries, it may be attributing cardiovascular deaths to DEHP that are actually caused by well-known risks like smoking or poor healthcare access.

More on hazard ratios

For a typical retrospective study the rule of thumb is that an HR of 2.0 (double the risk) is likely to be meaningful, but the closer the number is to 1.0 the less valid any conclusion will be. Although the confidence interval here excludes 1.0 — making the result technically statistically significant — the effect is still marginal.

Also, the HR is reported as 1.10 (95% CI 1.03–1.19). The fact that the HR resides within the variation means that the results are statistically significant but quite possibly not clinically significant. (If the HR is not within the confidence interval (CI) the results are not significant.) Even though this is not the case in this study, the fact that some of the participants had an HR of 1.03 (a 3% difference) is most likely measuring nothing.

Bottom line

Don't get me wrong. I think that there is WAY too much plastic produced and used globally and this is a serious problem if only for environmental concerns, even if there were no health concerns at all. But this does not warrant (IMO) an unnecessarily alarmist news story which will succeed only to scare consumers, many of whom are already frightened about far too much.

NOTES:

[1] An even more "prominent" endocrine inhibitor is bisphenol-A (BPA), which is still a boogeyman despite an enormous FDA study that concluded the chemical is safe as used.

[2] A retrospective study looks back in time using existing data to find links between past exposures and later health outcomes. It’s quicker than long-term studies but more prone to bias and missing information.

[3] NHANES (National Health and Nutrition Examination Survey) is a long-running public health surveillance program conducted by the National Center for Health Statistics (NCHS), part of the CDC. It has been collecting detailed health information from the U.S. population since the early 1960s.

https://www.acsh.org/news/2025/05/04/scary-plastic-study-should-probably-be-recycled-49453

Time to Fix the CDC – and Better Respond to the Next Pandemic

 75 years of preparation for an outbreak like that of COVID-19 – and yet, the CDC still failed to “reliably meet expectations” in addressing the crisis. That’s according to an August 2022 admission from Dr. Rochelle Walensky, President Biden’s Director of the Centers for Disease Control and Prevention (CDC).

This admission was stunning, but it was also unavoidable. The agency needs work.

As Walensky conceded, it failed to provide the public and public health authorities with clear and consistent messaging, and it failed to coordinate effectively with other public health agencies. It also failed at collecting and disseminating relevant data in real time to state public health authorities and the public more broadly.

Worse, its school closure guidance and COVID-19 vaccine recommendations (especially for children) were both politicized and incompatible with emerging data and risk/benefit analyses.

Much of the agency’s failure was a direct consequence of decades of congressional inaction. Congress ignored the growing need to strengthen the agency’s public health capabilities and give it the abilities necessary to safeguard our nation’s health. Even with the onset of COVID-19, the CDC was not the agency designated to lead in communicating daily with the nation. This was a big mistake.

The CDC cannot heal itself. But, by working with Congress, the Trump administration can fix the CDC, reorganizing its structure and refocusing its mission on its primary function: to detect, control, combat and prevent communicable diseases.

This is an enormous task. Health and Human Services Secretary Robert F. Kennedy Jr. has outlined some initial steps toward this end, but certain additional steps will be necessary.

First, Congress should formally authorize the CDC in statuteThe House Subcommittee on Oversight and Investigations, among others, recommended that Congress clarify the CDC’s role and responsibility as the lead federal agency in controlling infectious disease.

At the same time, Congress should end bureaucratic duplication and “mission creep” by transferring certain CDC functions to other agencies within HHS that are better suited to execute them.

For example, the CDC’s health promotion and disease prevention activities should be transferred to the newly created Administration for a Healthy America (AHA). Similarly, its National Center for Health Statistics could be transferred to the Agency for Health Quality Research, and its biomedical research should be transferred to the National Institutes of Health (NIH).

Congress also needs to target sufficient funding to establish and maintain a real-time national public health data system – one which lawmakers should then vigilantly oversee to ensure its efficient functioning. Congress previously attempted this under my (Robert Redfield’s) tenure as CDC Director, but it invested too little to accomplish the mission.

Congress and the administration must also improve and upgrade the reporting of adverse vaccine events. Today, CDC and the Food and Drug Administration (FDA) jointly administer the Vaccine Adverse Event Reporting System (VAERS). But this system is defective in that it relies on unverified patient self-reporting, making it incapable of determining a causal relationship between vaccines and specific injuries.

Fixing this system is key to combating today’s dangerous vaccine hesitancy and rebuilding the public’s confidence in vaccines. But the solution requires both accurate information and rapid response.

Given its long experience and institutional responsibility for determining drug safety and effectiveness, the FDA (which, unlike the CDC, is a regulatory agency) should be given sole responsibility for post-market vaccine surveillance. Congress should ensure that FDA has the necessary capacity to monitor adverse vaccine events and intervene quickly to protect the public from vaccine injuries.

While some responsibilities should be reassigned from the CDC to other agencies, other tasks should be restored to it.

In keeping with the CDC’s primary mission, Secretary Kennedy rightly decided to restore management of the Strategic National Stockpile (SNS) – the national repository for medical equipment and supplies – to the CDC.

In 2018, the SNS was taken over by the Administration for Preparedness and Response, a subagency within HHS. But the Government Accountability Office (GAO) soon determined that its management of the SNS was deficient.

Unfortunately, the problems with the SNS spanned both Democratic and Republican administrations. These problems, particularly insufficient inventories, contributed to the shortage of critical supplies early in the COVID-19 pandemic.

Pursuant to Secretary Kennedy’s direction and effective congressional oversight, the restoration of the CDC’s management of the Strategic National Stockpile will improve the nation’s readiness to cope with the next pandemic. With the appropriate inventories of critical medical supplies, medications and equipment, we can avoid a repeat of the COVID-19 failures.

Another way to improve the performance of the agency in a pandemic is by transferring the CDC headquarters from Atlanta to Washington, D.C. In a national medical emergency, the Director of the CDC should have immediate face-to-face access to the president, the HHS secretary, and other federal officials, as well as congressional leadership. Time-consuming travel, Zoom calls, or other online communications will not suffice for the kind of deliberation and debate necessary to forge complex and timely policy responses during a pandemic.

The CDC is dominated by career officials, but policy development requires prudent judgment – not just managerial, technical, or scientific expertise – to calibrate a careful balance of competing public goods. Therefore, the Trump administration should increase the number of non-career or “political” appointees to assist the director in formulating, communicating, and executing agency policies.

The administration should also decentralize agency operations to enable better federal-state communication and data sharing. During the pandemic, the CDC didn’t just fail to communicate effectively with state public health officials – it also frequently failed to get on-the-ground information from states and localities.

As Professor Emeritus Donald F. Kettle at the University of Maryland observed, “In the U.S., there simply wasn’t any mechanism for collecting nationally what the states and their cities were learning, and that handicapped the American response. In fact, one of the most profound American breakdowns was the failure even to recognize that this was an essential question in desperate need of a solid answer.”

Beyond improvement in CDC’s data collection and dissemination, we should also facilitate more direct interaction between CDC and state agency staff. We should establish CDC offices in states and major cities so the agency can collect and quickly analyze state-level data and help state and local agencies coordinate responses to emerging national emergencies.

Finally, the Trump administration should create a joint CDC/DOD task force. We live in an increasingly dangerous world, making it essential that biosecurity become a top U.S. priority.

Often, epidemics and outbreaks occur in politically insecure areas of the world, and a joint CDC/DOD unit may be able to respond with the necessary speed. A preponderance of the evidence points to the deadly COVID-19 pandemic as originating from a genetically manipulated coronavirus in the Wuhan Institute of Virology in China. Moreover, the lack of effective tracking of gain-of function viral research around the globe and the potential of biological warfare conducted by sinister international actors heightens the threats to our national security.

We cannot and should not depend on the World Health Organization (WHO) to protect us. The WHO already failed us during COVID-19, disregarding warnings from Taiwan and taking Chinese communists at their word; indeed, in January 2020 it broadcasted the lie that the novel coronavirus was not transmissible from human to human, and it even initially opposed travel restrictions to and from China.

In its final report, the House Select Subcommittee on the Coronavirus Pandemic concluded, “Throughout the pandemic, the WHO shied away from placing any blame on the CCP [the Chinese Communist Party]. Dr. Tedros [WHO’s Director General] even went so far as to praise the CCP’s ‘transparency’ during the crisis, when, in fact, the regime consistently lied to the world by underreporting China’s actual infection and death statistics.”

Instead of relying on the WHO for protection, the Trump administration should establish a top-tier task force of scientists and biowarfare experts from the CDC and the Department of Defense (DOD) to keep abreast, day and night, of emerging biosecurity threats to the U.S. and its allies. The agencies must also jointly deploy staff abroad to monitor public health threats overseas and be ready to respond to them in real time.

Protecting America from the next pandemic first requires improving the CDC and clarifying its core mission as the lead agency to combat a pandemic. By implementing these key organizational changes, Secretary Kennedy and his new team can greatly improve the CDC’s performance, enabling it to be better prepared to respond quickly, communicate clearly, and thus effectively protect us from the ravages of the next pandemic.

Robert Redfield, M.D., is a former Director of the CDC and Senior Visiting Fellow for Biosecurity and Public Health Policy in The Heritage Foundation’s Center for Health and Welfare Policy.

Robert Moffit, Ph.D., is a Senior Research Fellow in Heritage’s Center for Health and Welfare Policy, and was formerly a Deputy Assistant Secretary at HHS during the Reagan Administration.

https://www.realclearhealth.com/articles/2025/05/06/its_time_to_fix_the_cdc__and_better_respond_to_the_next_pandemic_1108272.html

Medicaid Is Not A Test Lab For Foreign Price Controls

by Sally Pipes 

In a desperate bid to claim fiscal discipline without touching entitlements, President Donald J. Trump is pushing congressional Republicans to adopt a “most favored nation” (MFN) drug pricing model for Medicaid. This policy would tie Medicaid reimbursements to the lowest prices paid in other developed countries—countries where government officials dictate drug prices under threat of coercion, patent confiscation, or market exclusion.

Let’s be clear: MFN is price fixing. It is not market reform. It is not a tough negotiating tactic. Republicans who fall for this scheme are abandoning any pretense of free-market principles.

Medicaid doesn’t need price controls from other countries; it already imposes them here. Under the program’s existing “Best Price” rule, manufacturers must offer Medicaid the lowest price they give to any other buyer, plus pay steep, mandatory rebates. The result? Medicaid receives average discounts exceeding 50%.

For many drugs, manufacturers are already forced to sell at a loss—what’s euphemistically called a “negative price.” That means the government not only takes the medicine, it also demands a cash payment for doing so. MFN would make this problem exponentially worse by anchoring Medicaid’s drug pricing to markets where prices are dictated by bureaucratic fiat.

In practice, this could force companies to stop offering their drugs in Medicaid entirely. And thanks to federal law, exiting Medicaid also means forfeiting Medicare Part B coverage. One act of economic illiteracy would therefore sabotage both Medicaid and Medicare simultaneously.

MFN proponents like to frame the policy as a way to stop “foreign freeloading.” But there's nothing tough or strategic about adopting the failed price-fixing systems of Europe or Canada.

International reference pricing is not a neutral benchmark. Countries like France and the UK don’t “negotiate” prices—they dictate them. When manufacturers refuse, they are locked out of the market entirely and risk patent theft through compulsory licensing. In Germany, a drug’s price is set after one year based on whether a government board deems it “more effective” than existing options—a bureaucratic exercise so flawed that it regularly rejects FDA drugs that physicians consider groundbreaking.

Importing foreign price controls is not a clever budget tactic. It’s surrendering to extortion.

Proponents of MFN like to gloss over its long-term effects. But we don’t have to speculate—decades of data already show what price controls do to innovation.

It costs over $2.6 billion to develop a new drug largely because the failure rate is staggering; fewer than 8 in 100 drugs that enter clinical trials ever reach patients. Yet more than two in three new medicines are developed in the United States because our system still allows innovators to earn a return on successful products.

That incentive structure is precisely what MFN would destroy.

The Congressional Budget Office has noted that “the amount of money that drug companies devote to R&D is determined by the amount of revenue they expect to earn from a new drug.” By slashing expected returns, MFN would decimate research and development budgets—meaning fewer new cures and treatments, and more preventable deaths.

MFN would also deepen the dysfunction of the 340B program—a cronyist distortion of the drug market that has ballooned beyond its original mission and inflates costs for employers and taxpayers.

340B prices are pegged to Medicaid rebate formulas. Cut Medicaid prices through MFN, and 340B discounts expand automatically. That means hospitals and clinics participating in the program—most of which resell those discounted drugs to private insurers at massive markups—reap even larger windfalls.

Instead of doubling down on price controls, Republicans should get serious about structural Medicaid reform.

Rep. Chip Roy, R-Texas, and 19 of his House colleagues have outlined exactly the right approach: restore fiscal responsibility to Medicaid through block grants or per-capita caps, tighten eligibility verification, and align incentives with outcomes. Without serious reform, Medicaid’s current trajectory will necessitate massive tax hikes and benefit cuts across the board.

That’s the choice. It’s either real reform now—or fiscal collapse and rationing later.

The MFN proposal isn’t tough on foreign freeloaders. It’s soft on math, hostile to innovation, and blind to the realities of drug development. It would make Medicaid more expensive, less effective, and more dangerous—not just to patients, but to the future of American medicine.

The real solution isn’t to copy the failures of other countries. It’s to lead with principle—and reform.

https://www.forbes.com/sites/sallypipes/2025/05/03/medicaid-is-not-a-test-lab-for-foreign-price-controls/

C4 Therapeutics Shelves BRAF Blocker, Goes All-In on Multiple Myeloma Drug

 

The Massachusetts biotech will focus its efforts and resources into cemsidomide, an oral drug candidate being trialed for multiple myeloma and non-Hodgkin lymphoma.

C4 Therapeutics will no longer pour money into its investigational BRAF inhibitor CFT1946, in the name of “strategic capital allocation,” the biotech announced Wednesday.

Instead, C4 will focus its efforts and resources on its multiple myeloma drug candidate cemsidomide, while looking for development partners that can “advance the BRAF program given the high unmet need and strong degrader rationale for treating BRAF V600 mutant solid tumors.”

Before being put on the backburner, CFT1946 had a Phase I readout last September, which demonstrated that the drug candidate had an encouraging pharmacokinetic and safety profile, according to the company.

These early results underscored the potential of CFT1946 to “disrupt the current treatment landscape” in these specific solid tumors, CEO Andrew Hirsch said at the time. BRAF is a signaling protein that frequently carries a V600 mutation in a variety of cancer types.

Data from a Phase I dose-escalation study of CFT1946 in patients with melanoma or colorectal cancer will be presented at an upcoming scientific congress, according to C4’s press announcement on Wednesday.

C4 announced its decision to put CFT1946 on ice alongside its first-quarter earnings report. In the first three months of 2025, the biotech recorded a net loss of $26.3 million, a slight improvement from its $28.4 million deficit during the same period last year. By the end of Q1, C4 had $234.7 million in cash, cash equivalents and marketable securities, enough to keep it afloat into 2027.

The Massachusetts-based biotech will now focus its efforts and resources on cemsidomide, an experimental oral degrader of IKZF1/3 transcription factors being trialed for multiple myeloma. According to C4, Phase I data for the drug candidate suggest a “compelling” response profile for cemsidomide in this indication, hitting an overall response rate of 50% as of an April 30 data cutoff.

C4 plans to wrap up the Phase I dose-escalation trial for cemsidomide and present its data by the third quarter.

Aside from multiple myeloma, C4 is also studying cemsidomide in non-Hodgkin’s lymphoma, for which it is also conducting Phase I dose-escalation analyses. The biotech is building up to a readout in this indication by year-end. C4 is awaiting certain “regulatory feedback” regarding cemsidomide’s registrational development, which it expects to receive by mid-year.

https://www.biospace.com/business/c4-therapeutics-shelves-braf-blocker-goes-all-in-on-multiple-myeloma-drug

CRISPR’s Casgevy on the Rise With More Gene Therapy Proof of Concept To Come in 2025

 

CRISPR Therapeutics’ partner Vertex reported that more than 65 treatment centers have been activated for the gene therapy Casgevy. While Vertex handles the market, CRISPR has been focused on its clinical program.

The outlook for CRISPR Therapeutics’ approved gene therapy Casgevy is starting to look up, with more treatment centers added over the past quarter. The positive trend comes just as the gene editing biotech reported that its cholesterol-lowering gene therapy dropped lipoprotein and triglycerides in a Phase I trial, showcasing the potential of gene therapy if the space can overcome its commercial hurdles.

CRISPR’s partner Vertex reported earlier this week that more than 65 treatment centers have been activated for Casgevy, which is approved for sickle cell disease and beta-thalassemia. The revelation provided a glimmer of hope for the gene therapy space, which has been battered by bad news.

Vertex reported revenue of $14.2 million for Casgevy in the first quarter, up a modest but encouraging 4%, according to William Blair analysts. This growth signals that “the ramp in patient starts is beginning to convert to a ramp in cell infusions,” the group wrote in a note to investors Wednesday morning.

In September 2024, patients finally started to receive infusions of Casgevy, 10 months after its December 2023 approval. It’s been a slow build for a modality that could have profound impacts on the lives of patients. The treatments have struggled to gain market share; they are expensive and challenging for patients to undergo. The companies involved have also had to build out a network of treatment centers capable of supporting patients through the process.

As CRISPR and Vertex have charged ahead, rival bluebird bio has fallen behind. Once a promising gene therapy company, bluebird sold itself to private equity earlier this year for a mere $30 million after failing to reach profitability in time to make up a looming cash gap.

But CRISPR has the backing of a much larger pharma company in Vertex, which has been leading the marketing efforts. Vertex has set a goal of activating 75 treatment centers globally, and has hit 65 already, Chief Operating Officer Stuart Arbuckle explained on Vertex’s first quarter earnings report Monday.

“Casgevy truly does have the potential to be a multibillion-dollar product for Vertex,” Arbuckle said.

About 90 patients have undergone the initial cell collection process, according to Arbuckle, and more than twice that number have been referred to begin treatment. A total of eight patients have completed treatment.

“It’s been inspiring to hear that Casgevy patients now feel able to live their lives in ways they never have before,” Arbuckle said. “Whether that means having the energy to play with their kids, taking up snowboarding without fear that the cold might bring on a pain crisis or investing in their education and careers given expectations now for a longer and healthier life. It is a privilege to be part of their journey.”

Laser-Focused

While Vertex handles the market, CRISPR has been cleared to focus on its clinical program, such as the in vivo liver editing program CTX310. On Tuesday, the company reported a small batch of data from just 10 patients with elevated lipoprotein (LDL) and triglyceride (TG) levels in a first-in-human trial of the gene therapy. A single dose of the treatment decreased expression of the ANGPTL3 gene, which is involved in the regulation of LDL and TG levels. Both LDL and TG decreased as well.

One patient with severe hypertriglyceridemia had an 82% reduction in TG. Another with heterozygous familial hypercholesterolemia had an 81% reduction in LDL-C, a measure of the cholesterol carried by LDL particles.

William Blair said the data “looks competitive” with LDL-C reductions seen with Arrowhead Therapeutics ARO-ANG3 and Regeneron’s approved therapy Evkeeza.

CTX310 was well tolerated and there were no severe adverse events reported. CRISPR also noted that liver enzymes were not elevated at any dose level.

CRISPR heralded the results as a “significant milestone” for its proprietary lipid nanoparticle (LNP) delivery technology for gene editing in the liver. More data from the Phase I trial will be presented at a medical meeting later this year. CRISPR is also developing CTX320 for cardiovascular disease, with a Phase I readout expected in the second quarter.

“We also think the safety profile of CTX310 de-risks the upcoming readout from CTX320, and we highlight that CRISPR is the only company with an in vivo gene-editing candidate targeting Lp(a) in the clinic,” William Blair said.

The company is also working on two preclinical programs, CTX340 for refractory hypertension and CTX450 for acute hepatic porphyrias. In oncology, CRISPR will have a readout for a Phase I trial of CTX131 in solid tumors and blood cancers sometime this year. An update for the regenerative medicine diabetes treatment CTX211 is also expected before the end of 2025.

“We view CRISPR as having a catalyst-rich 12-month period ahead as it advances candidates across its ex vivo and in vivo platforms through the clinic,” William Blair wrote.

https://www.biospace.com/business/crisprs-casgevy-on-the-rise-with-more-gene-therapy-proof-of-concept-to-come-in-2025