AstraZeneca boss: I don't think I would do anything differently

 The head of the drugs giant behind the Oxford-AstraZeneca Covid-19 vaccine says the jab managed to save a million lives despite facing "setbacks".

AstraZeneca boss Pascal Soriot also addressed studies linking the vaccine to rare but dangerous blood clots.

Looking back on its development, he said: "I don't think I would do anything differently from what we did."

Many countries in Europe and Asia have placed age restrictions on the vaccine and the US has yet to approve it.

Mr Soriot received a knighthood in the Queen's Jubilee birthday honours last week for his contributions to science.

He was honoured for services to the UK in "life sciences and leadership in the global response to the Covid pandemic", AstraZeneca said in a statement on Wednesday.

Mr Soriot, who is chief executive of the British-Swedish firm, told the BBC during a recent visit to Singapore that the vaccine's quick development and distribution prevented a million people from dying of Covid-19.

He said this came despite "setbacks" including concerns around rare but dangerous blood clots, which emerged last year.

"We decided to do it at no profit, we decided to partner with a network of partners around the world to scale up manufacturing. Despite the setbacks, we delivered three billion doses [of the vaccine] and saved a million lives," he said.

"When you launch yourself in something like this, which is a huge undertaking, you have to accept that you will have setbacks," he added.

AstraZeneca developed the vaccine in collaboration with the University of Oxford. It was first approved by the UK in December 2020 as countries raced to contain the growing numbers of coronavirus infections.

Nearly half of the adult population in the UK has received two doses of the vaccine, where it is believed to have saved more lives to date than the Pfizer and Moderna jabs combined.

Last year, UK regulators recommended the AstraZeneca jab for over-40s after its use was linked to extremely rare blood clots.

According to the UK's Medicines and Healthcare products Regulatory Agency, the risk of developing a blood clot was about four in one million.

However, many other European countries suspended their use of the vaccine. They only lifted their curbs and put age restrictions on the jab when European Union (EU) regulators declared that the benefits outweighed the risks.

The restrictions mean AstraZeneca's vaccine is now approved for use for a smaller segment of the population than several other Covid vaccines.

Mr Soriot said: "It is important to remember that those side effects are extremely rare. When you start vaccinating millions of people, very rare side effects will emerge that remain very rare. And this is common to all vaccines."

EU regulators only approved the vaccine's use as a "third dose booster" for adults last month.

Although the vaccine can be safely refrigerated for up to six months, several African states have destroyed or returned their stocks, as they said they could not use the jabs before they expired.

Meanwhile, Mr Soriot said in less developed economies - including in Asia - some people were reluctant to get vaccinated.

"In the emerging, developing countries, there's quite a bit of hesitancy. Of course, China is a different story where they're still managing a 'zero-Covid' policy. So it depends where you are in the world," he added.

Mr Soriot said the firm was still in discussions with US authorities about submitting the vaccine for approval in the country, as the "need for a new vaccine is much less in the US than it was".

"Today, there is [an] over supply. We do have too many vaccines. So the question is how do we deliver? How do we administer those vaccines and how do we manage vaccine hesitancy? So we are in a very different place," Mr Soriot said.

In November, AstraZeneca said it will move away from providing its Covid vaccine to countries on a not-for-profit basis, as the disease was becoming endemic.

It said it expected to make a modest income from the vaccine from a series of for-profit agreements.

The jab will continue to be supplied on a not-for-profit basis to poorer countries.

https://www.bbc.com/news/business-61671715

Elections Won't Fix This

 by Jeffrey Tucker via The Brownstone Institute,

Americans have limitless faith in democracy. In the early 19th century, that charmed Alexis de Tocqueville. His book Democracy in America still rings true today because not much has changed. The entire country can be in ruins and even then, most people figure that it will all be improved or even solved come November. It’s been going on for our entire history. As a people, we believe our elections are what keep the people and not the dictators in charge. 

Surely some of this faith is necessary simply because it is the only option we have. The sitting president and his party are in deep trouble now, and most observers are predicting a rout in the midterm elections, granting us two additional painful years of inflation plus recession unfolding amidst what will surely be a brutal political stalemate and cultural upheaval. Then November will come again and with it another round of trust that the new president will figure something out. 

This faith in our elected leaders is belied by the experiences of the last 30 months. To be sure, the elected politicians are nowhere near blameless in what unfolded and they could have done far more to stop the disaster. Trump could have sent Fauci and Birx packing (maybe?), the Republicans could have voted no on trillions in spending (did they really have a choice?), and Biden could have renormalized the country (why didn’t he?). Instead they all went along…with what? With advisers from the bureaucracies, the people who have de facto ran the country for this entire grim period. 

Reading Scott Atlas’s book, one comes away with a very strange picture of how Washington worked in the first year of the pandemic. Once Trump gave the green light to lockdowns, the permanent bureaucracy had all it needed. In fact, this happened even before Trump approved it: the Department of Health and Human Services had already released its lockdown blueprint on March 13, 2020, a document which had already been weeks in the preparation. After the March 16 press conference, there was no going back. The “deep state” – by which I mean the permanent non-appointed bureaucracy and the pressure groups to which it answers – was running the show. 

The administrative state has probably not enjoyed such a good run since World War II or perhaps much earlier if ever. These were certainly the salad days. Merely by assigning a bureaucrat to type on a screen, the CDC could cause every retail business in the US to install plexiglass, force people to stand 6-feet apart, make the human face publicly invisible, close or open whole industries at will, and even scrap religious services and singing. To be sure, these were mere “recommendations” but states, cities, and corporations deferred for fear of liability should something go wrong. The CDC provided the cover but acted pretty much like a dictator. 

We know this for certain given the CDC’s response to the Florida’s judge’s decision to declare the transportation mask mandate illegal. The response was not that the mandate was both compliant with the law and necessary for public health. Instead, the agency and the Biden administration too rallied around a simple point: the judge’s decision cannot stand because courts should have no authority to override the bureaucracy. They actually said it: they demand total, unchecked, unquestioned power. Period. 

This is alarming enough but it speaks to a much larger problem: a hegemonic bureaucratic class that is not controlled by the political class and believes that it possesses total power. The implications extend far beyond the CDC. It applies to every executive agency of the federal government. They ostensibly operate under the authority of the office of the president but actually not even that is true. There are severe restrictions in place on the ability of the elected president to fire anyone among them. 

Trump couldn’t fire Fauci, at least not easily, and he was told this repeatedly. That pertains to millions of other employees in this category. This was not the traditional American system. In the days before 1880, it was routine for new administrations to toss out the old and bring in the new, and yes of course that included cronies. 

That system came to be derided as the “spoils system” and it was replaced by the administrative state with the Pendleton Act of 1883. This new law was passed in response to the assassination of President James Garfield. The culprit was an angry job seeker who had been rebuffed. The supposed fix, backed by Garfield’s successor Chester A. Arthur, was to create a permanent civil service, thus supposedly reducing the incentive to shoot the president. It initially pertained to only 10% of the federal workforce, but it had developed vast power by the time of the Great War. 

It wasn’t until I read Alex Washburne’s piece on Brownstone that the full implications became obvious to me. He cites the existence of something called the Chevron doctrine of deference to the agency. Whenever there is a question of an agency’s interpretation of the law, the court should defer to the agency and not to a strict reading of the law. Getting curious about this, I clicked through to the Wikipedia entry on the topic. 

Here is where we find the amazing revelation: this egregious rule came about only in 1984! The case in question was Chevron U.S.A., Inc. v. Natural Resources Defense Council, Inc. and the issue concerned the EPA’s interpretation of a Congressional statute. John Paul Stevens wrote in the majority opinion:

“First, always, is the question whether Congress has directly spoken to the precise question at issue. If the intent of Congress is clear, that is the end of the matter; for the court, as well as the agency, must give effect to the unambiguously expressed intent of Congress. If, however, the court determines Congress has not directly addressed the precise question at issue, the court does not simply impose its own construction on the statute . . . Rather, if the statute is silent or ambiguous with respect to the specific issue, the question for the court is whether the agency’s answer is based on a permissible construction of the statute.

All of this begs the question of what is permissible, but the critical thing is the dramatic shift in the burden of proof. A plaintiff against an agency must now demonstrate that the agency’s interpretation is impermissible. In practice, this rule has granted tremendous latitude and power to executive agencies to rule the whole system with or without political permission. 

And keep in mind what the chart looks like. 

The lower two-thirds of this chart is increasingly the government as we know it, and its power is unaccountable to the president, to Congress, to the courts, or to the voters. From what we know about the operations of the FDA, DOL, CDC, HHS, DHS, DOT, DOE, HUD, FED, and so on throughout every combination of letters you can think of, is that they are typically captured by private interests powerful enough to buy themselves influence, complete with revolving doors in and out. 

This creates a governing cartel that is a formidable force against democracy and freedom itself. This is a major and highly significant problem. It’s not clear that Congress can do anything about it. Worse, it’s not clear that any president or any court can really do anything about it, at least not without facing a barrage of brutal opposition, as Trump learned first hand. 

The administrative state is THE government. Elections? They provide just enough difference to lead people to believe they are in charge, but are they? Not according to the organization chart. This is the real problem with the US system today. This system cannot be found in the US Constitution. No one alive voted for it. It just gradually evolved – metastasized – over time. The last 30 months have demonstrated that it is a real cancer eating out the heart of the American experience, and not just here: every country in the world deals with some version of this problem. 

Americans’ romance with democracy continues unabated and right now, everyone I know is living for the great day in November when the existing crop of elected leaders can be shown a thing or two. Good. Throw the bums out. The question is: what should the new class of elected leaders do about this much deeper problem? Can they do anything about it even if they had the will? 

Keep in mind that it pertains not just to the public-health bureaucracies but to every aspect of public life in America. It’s going to take far more than a few elections to fix this. It is going to require focus and public support for a restoration of a genuine constitutional system in which the people rule with their elected leaders as their representatives, without the vast meta-layer of state control that pays no attention to the comings and goings of the elected class. 

In sum, the problems are much deeper than most people realize. These problems have been on display for the public in these past two-plus years. During this time, American life as we knew it was upended by an unaccountable administrative bureaucracy – in Washington but with reach into every state and city – that ignored the Constitution, evidence, public opinion, the pronouncements of elected leaders, and even the courts. 

Instead, this machinery of coercion ruled in concert with a network of private-sector actors, including media and financial companies, that have outsized influence and routinely use these agencies as weapons in their own economic interests at the expense of everyone else. 

This system is indefensible. Experiencing it first hand in the 1950s, Dwight Eisenhower decried the entire machine in his farewell address of 1961. He warned of the “danger that public policy could itself become the captive of a scientific-technological elite.” It is the task of statesmanship, he said, to uphold “the principles of our democratic system – ever aiming toward the supreme goals of our free society.”

Uprooting the entrenched, arrogant, hegemonic, and unaccountable administrative state that believes it operates with no limit to its power is the great challenge of our time. The public is probably nowhere near aware of the full extent of the problem. Until voters themselves figure it out, the politicians will have no mandate even to test a solution. 

https://www.zerohedge.com/political/elections-wont-fix

Illumina sequencing devices vulnerable to critical hacking risks: FDA

 Illumina has discovered multiple cybersecurity flaws in software embedded in several of its genetic sequencing instruments, potentially opening a door for hackers to access or alter patients’ sensitive health data, the FDA warned in a June 2 notice to healthcare providers.

The affected sequencers include the NextSeq 550Dx, MiSeqDx, NextSeq 500, NextSeq 550, MiSeq, iSeq and MiniSeq devices. They span a mix of indications: for research use only, clinical use—to sequence a patient’s DNA or diagnose genetic conditions—or a combination of both.

Illumina began alerting clinical diagnostic labs and researchers who use the devices to the hacking risks in early May, when it sent notices to all affected customers. The company has already put out a short-term software patch for the cybersecurity issues, which all users are asked to immediately download and install. A permanent fix is in the works.

“We are supporting our customers to install the software patch for this issue immediately and to promptly implement the long-term solution when available. Illumina will continue to assess and enhance our systems to maintain a strong cybersecurity posture to support continuous innovation in healthcare,” Illumina said in a statement (PDF). “It is essential that all participants in the connected healthcare system are proactive and vigilant about cybersecurity, including adopting best practices and implementing short- and long-term solutions to identified vulnerabilities.”

The issue revolves around the Local Run Manager software used in the sequencers to design sequencing runs, monitor run status, analyze genomic data and access the results of each analysis. The software can be accessed either directly through the devices’ online platforms or in an off-instrument version, depending on the device.

Illumina identified five specific cybersecurity risks within the software, three of which garnered a score of 10 on the common vulnerability scoring system (CVSS)—indicating the highest possible risk level—according to a notice from the U.S. Department of Homeland Security’s Cybersecurity and Infrastructure Security Agency, or CISA.

The three most critical openings create instances where an unauthorized person could remotely upload and execute malicious code to the software, potentially giving them access to private sequencing data and allowing them to change the software’s settings and configurations, resulting in inaccurate genetic analyses.

Another vulnerability was given a CVSS score of 9.1—still within the “critical” range—and could allow a hacker to “inject, replay, modify and/or intercept sensitive data,” per CISA, since the software doesn’t automatically require authentication or authorization for access.

The final flaw scored a 7.4 on the CVSS, indicating a “high” severity. It stems from the fact that certain versions of the Local Run Manager program haven’t implemented transport layer security encryption, potentially giving a bad actor the ability to intercept sensitive data as it’s sent from the sequencer to the analysis software.

Neither Illumina nor the FDA has received any reports of the vulnerabilities being exploited, the agency said.

In the meantime, as the company continues to develop a long-term fix for the issues, it “strongly advised” users to implement firewalls and other privacy tools to restrict both inbound and outbound access to the software, and to deploy the sequencing tech within the smallest subsection of a facility’s network possible, using only trusted devices.

https://www.fiercebiotech.com/medtech/illuminas-sequencing-devices-vulnerable-critical-hacking-risks-fda-warns

ASCO: Clovis CEO defends Rubraca's ovarian cancer win as FDA wants more

 In the hopes of catching up with AstraZeneca and GSK, Clovis Oncology recently trotted out a broad trial success that supported bumping up Rubraca in the ovarian cancer treatment order.

But when the FDA asked for more data, concerns started to grow that the agency had seen some worrying signs in the trial data that weren’t made public.

Now, with a full-on presentation at the 2022 American Society of Clinical Oncology annual meeting, Clovis CEO Patrick Mahaffy hopes to clear the air. Refuting the FDA, he argues that existing data should be enough to support an application for Rubraca in patients with newly diagnosed ovarian cancer after an initial round of chemotherapy.

“There is absolutely nothing—nothing at all” that people should be concerned about in Rubraca’s ATHENA-MONO phase 3 data, Mahaffy said in an interview with Fierce Pharma.

That doesn't mean the FDA will agree. But Mahaffy aims to make his case.

As Clovis previously announced, under an investigator analysis, Rubraca slashed the risk of disease progression or death by 48% over placebo in all patients regardless of tumor biomarker status in front-line maintenance treatment of ovarian cancer. By assessment of a blinded independent review panel, the risk reduction was 53%.

PARP inhibitors like Rubraca typically work better in BRCA-mutated cancer or, more broadly, tumors with homologous recombination deficiency (HRD). But Rubraca also showed a benefit in HRD-negative patients, paring down the risk of progression or death by 35% under investigator analysis or by 40% according to the independent review.

The numbers look on par with—or even better than—those GSK’s Zejula posted in its own first-line maintenance study. In the phase 3 PRIMA trial, Zejula reduced the risk of disease progression or death by 38% in the overall population and 32% in HRD-negative patients. AstraZeneca and Merck’s leading PARP inhibitor, Lynparza, isn’t allowed in HRD-negative patients, who represent about half of the entire ovarian cancer population. 

Investigator-assessed PFS for HRD-negative patients
in the Athena-Mono trial (Bradley Monk, et al/ASCO 2022)

The progression-free survival curves between Rubraca and placebo remain separated in ATHENA-MONO, indicating an ongoing advantage for the Clovis drug. But by investigator analysis, the curves appear to be nearing a crossing among patients with HRD-negative tumors.

Mahaffy played down the trend observed in the subgroup analysis, arguing it’s not statistically powered and that the investigators don’t find it worrisome, either.

Then what’s causing the additional FDA scrutiny? A renewed FDA focus on patient survival. According to Mahaffy, the agency is “looking to ensure that there is no decrement.”

The concern stemmed from the ARIEL4 trial. As a postmarketing study of Rubraca’s third-line BRCA-mutated ovarian cancer indication, ARIEL4 showed that in patients who had already received two or more lines of chemo, the Rubraca takers' lives were shorter than the chemo group's. The Clovis drug was linked to a 31.3% increased risk of death, the study showed.

But Mahaffy noted it was the platinum-resistant subgroup, with their 51.1% increased risk, that pulled Rubraca back. The drug’s data in platinum-sensitive patients were the same as Lynparza’s in a separate platinum-sensitive-only trial dubbed SOLO3. Plus, ARIEL4’s overall survival analysis was “highly confounded by subsequent therapy,” Mahaffy said.

Still, in a recent securities filing, Clovis said the FDA has reviewed the ARIEL4 data, which may lead to the company withdrawing Rubraca’s third-line ovarian cancer indication in the U.S. and possibly in Europe as well.

For now, the ATHENA-MONO trial has yet to show a clear overall survival signal, as the risks of death were roughly the same between Rubraca and placebo. The data remain immature as only 25% of the deaths needed to calculated overall survival had occurred.

Previously, Zejula got its front-line maintenance nod for all patients regardless of biomarker status, despite the fact that only 11% of the required number of deaths had happened. At that time, investigators in Zejula’s PRIMA trial provided an estimated two-year survival rate, predicting that 84% of patients on the GSK drug would still be alive by that time point, versus 77% for placebo. Clovis currently doesn’t have those two-year estimates for Rubraca.

Seemingly spooked by the ARIEL4 data, the FDA is asking Clovis to run another ATHENA-MONO overall survival analysis at 50% death events before applying for approval. But as Clovis has noted, it’ll likely take another two years to collect those data.

Mahaffy argued that the current analysis, without any sign of harm to patient survival, should be able to support a filing. “If these data were to have been first disclosed two years ago, they would be equally compelling,” he said.

He pointed to a 2017 white paper on ovarian cancer clinical trial endpoints co-authored by FDA oncology chief Richard Pazdur, M.D. It stated that “the FDA posited that endpoints other than overall survival … could be acceptable for regulatory decision.”

Clovis now hopes to schedule another meeting with the FDA “in the next coming weeks,” Mahaffy told Fierce Pharma. “We want an opportunity for a more fulfilling discussion than we’ve had today.”

The company is “actively preparing” for both EU and U.S. submissions, the CEO said. The FDA has threatened to hold an advisory committee meeting to review the data should Clovis file with the existing information. But Mahaffy sees it as a door cracked open for a potential filing.

And Clovis needs to hurry. Without the large front-line maintenance ovarian cancer setting—which Mahaffy said is at least twofold larger than a second-line maintenance use—Rubraca sales have been declining. Clovis has publicly stated that it needs to raise additional capital, and Mahaffy said there’s an opportunity to potentially partner Rubraca up regionally.

https://www.fiercepharma.com/pharma/asco-clovis-ceo-defends-rubracas-ovarian-cancer-win-fda-wants-more-assurance

Novartis hit by cyberattack but says no sensitive data were compromised

 No one is immune from cyberattacks—not even pharmaceutical giants like Novartis.

Industrial Spy, a hacking group that runs an extortion marketplace selling stolen data, posted data allegedly stolen from Novartis, specialized IT website Bleeping Computer reported late last week. Luckily for the pharma company, it says no sensitive data was compromised in the attack.

The hackers claimed the data were stolen directly “from the laboratory environment of the manufacturing plant,” according to the description of the stolen data.

The data were likely stolen on Feb. 25, Bleeping Computer reports. The drugmaker told the publication it was aware of the matter and has thoroughly investigated it.

“We can confirm that no sensitive data has been comprised," the company told the website. "We take data privacy and security very seriously and have implemented industry standard measures in response to these kinds of threats to ensure the safety of our data."

Industrial Spy is also known to use ransomware in attacks, Bleeping Computer reports. In this case, there wasn't evidence that company devices were encrypted.

Switzerland ranks third among most targeted European countries for cyberattacks, behind Germany and the U.K., according to Switzerland insurance company Swiss Risk and Care. It’s the seventh most targeted country in the world.

A February report from digital risk protection company Constella Intelligence recorded more than 200,000 total data exposures and data breaches from 20 pharma companies. Of the total, 59% of total breaches and 79% of exposed records happened after 2020.

Pharma companies have been working to bolster their cyber defenses in recent years. Back in 2017, a cyberattack at Merck ended up costing the drugmaker more than $1 billion.

https://www.fiercepharma.com/pharma/norvartis-hit-cyber-attack-says-no-sensitive-data-was-compromised

Assembly Bio Commences Early-Stage Study of Drug to Treat Hepatitis B

Assembly Biosciences, Inc. 

ASMB-1.95%+ Free Alerts

 today announced Initiation of Phase 1b clinical study of its drug candidate ABI-H3733 for Chronic Hepatitis B Virus Infection

The Phase 1b clinical trial will evaluate the safety, pharmacokinetics and antiviral activity of 3733 in adults with chronic HBV (cHBV) infection.

This trial is supported by the results from previous Phase 1a study of 3733 showing a favorable safety and pharmacokinetic profile and will evaluate a new tablet formulation with the potential for convenient once-daily dosing.

ABI-H3733 (3733) is an investigational next-generation, highly potent core inhibitor.

John McHutchison, AO, MD, chief executive officer and president, commented : "This study initiation serves as an important milestone in the clinical development program for 3733, a promising candidate that has demonstrated increased potency against both HBV core inhibitor mechanisms and against cccDNA formation in particular, and advances our strategy to pursue finite and curative HBV therapies."

The company is scheduled to highlight additional details about the new tablet formulation of 3733 in a poster accepted for presentation at the Annual Meeting of the European Association for the Study of the Liver (EASL), will be held in London on June 22-26, 2022.

https://www.benzinga.com/general/biotech/22/06/27569937/assembly-bio-commences-early-stage-study-of-drug-to-treat-hepatitis-b-viral-infection