Valisure links 'unstable' Zantac and its ilk to carcinogen build-up, cancer risk

 When online pharmacy Valisure discovered high levels of a likely carcinogen in Zantac and its generic copycats in 2019, global recalls ensued. Contamination was one fear, but the bigger issue, as Valisure saw it, was the instability of the ranitidine molecule itself.

Now, the company has rolled out data supporting its suspicions that the once-popular heartburn med is inherently unsafe.

Valisure’s latest study, published in the Journal of the American Medical Association (JAMA) Network Open, suggests Sanofi’s Zantac and other ranitidine drugs can cause the suspected cancer agent N-Nitrosodimethylamine (NDMA) to form under a range of conditions, including in the human body.

In a separate study posted on the preprint server MedRxiv, the company noted a “significant association” between the H2-blocker’s use and increased breast, thyroid, bladder and prostate cancer diagnoses.

The NDMA scare began back in 2018 with recalls of “sartan”-based blood pressure drugs, extended through Zantac recalls and then to the popular Type 2 diabetes med metformin. Unlike the sartan meds and metformin—which were likely contaminated during the manufacturing process, experts say—ranitidine itself is the culprit, Valisure says.

The pharmacy's studies support “decades of research that ranitidine is fundamentally unstable, can form NDMA in a variety of conditions including in the human body and could be carcinogenic and toxic to humans,” David Light, founder and CEO of the company, said in a release.

For the JAMA Network study, Valisure used liquid chromatography-high resolution mass spectrometry (LC-HRMS) to detect the suspected cancer agent in simulated gastric fluid. The company varied pH, as well as nitrite and ranitidine concentrations, to assess possible NDMA formation under different conditions in the stomach. 

At the two-hour mark, researchers linked one 150-mg tablet of cool mint Zantac—mixed with a low-end concentration of sodium nitrite—to formation of 947 ng of NDMA. When the nitrite concentration was increased, the cool mint tablet yielded a maximum of 320,000 ng of the likely carcinogen. That's 320 micrograms—massively outstripping the 0.096-microgram NDMA concentration deemed safe for daily human consumption, a Valisure spokesperson confirmed via email. 

“Valisure detected NDMA in every brand and every dosage form of ranitidine that we tested whether over the counter or prescription and regardless of manufacturer,” Kaury Kucera, Ph.D., chief scientific officer at the company, added. “This appears to be a fundamentally different problem than NDMA contamination found in drugs like valsartan and metformin because it occurs in every brand of ranitidine and is inherent to the molecule itself.”

For its MedRxiv study, Valisure looked at 10,347 cancer patients. A cross-sectional analysis showed ranitidine use, versus other common heartburn drugs, was correlated with a higher risk of breast cancer. The researchers found similar links between ranitidine and thyroid, bladder and prostate cancer risk.

Valisure’s research is something of a post-mortem after 2019’s recall spree. Sanofi in late 2019 pulled all over-the-counter Zantac products from U.S. shelves, while Valisure's spokesperson said she was "not aware of any manufacturers still selling or distributing ranitidine products." 

Sanofi wasn't immediately available to comment. 

Valisure isn’t the only one to sound the alarm on ranitidine. A 2008 study from the Fred Hutchinson Cancer Research Center assessed the link between breast cancer risk and three major H2 blockers—cimetidine, famotidine, and ranitidine. After looking at more than 3,000 subjects, the researchers cleared famotidine and cimetidine, but they found ranitidine was “significantly associated” with a common form of breast cancer.

Valisure, meanwhile, brought NDMA to the forefront of drug safety conversations in 2018 when it detected the likely carcinogen in the blood pressure drug valsartan, which in turn led to its own spate of recalls.

In 2020, the plot thickened when Valisure identified NDMA in certain batches of the popular diabetes drug metformin. More than a half-dozen manufacturers, from Lupin to Sun Pharma to the U.S.’s Nostrum Laboratories, had to pull their metformin products, and the recall parade has already bled over into 2021.

Product pulls for metformin and “sartan” blood pressure drugs have been tied to contamination specifically, and Valisure noted that, so far, epidemiological studies have failed to link valsartan use to any human cancers.

https://www.fiercepharma.com/pharma/valisure-links-unstable-zantac-and-its-ilk-to-carcinogen-build-up-cancer-risk

Covid-19 vaccine pipeline builds as Clover and Dynavax push on

 Several late-stage Covid-19 vaccine successes have not deterred developers working on earlier projects, and today Clover became the latest to announce a move into phase II/III, with a vaccine codenamed SCB-2019. The move is notable because the China biotech is proceeding with a Dynavax adjuvant, rather than one made by Glaxosmithkline. A study of both vaccine-adjuvant combinations found that immune responses were lower when SCB-2019 was adjuvanted with Dynavax’s CpG/Alum, as opposed to Glaxo’s AS03, though the authors stressed that the data could not be extrapolated to infer protection. Clover apparently saw enough to push on with CpG/Alum, although it might not have had a choice; Glaxo could well have chosen to prioritise the two other vaccine projects that utilise AS03. The adjuvant is also being used in a Medicago project, and in the delayed Sanofi vaccine collaboration. A spokesperson for the UK pharma giant told Evaluate Vantage that manufacturing capacity had no bearing on the move. With big names in vaccine development failing to progress it is encouraging to see a full pipeline coming behind the leaders, although maybe the bar to push on is lower for those with smaller commercial vision.

Coming behind: the second wave of Covid-19 vaccines?
Project	Description	Company	Update
CVnCoV	mRNA (2 dose)	Curevac	Herald, Europe ph2/3 data due Q1 2021; Europe ph3 due 2021
Ad5-nCoV	Adenovirus type 5 vaccine (1 dose)	Cansino Biologics	Ph3 recruiting in Russia & S America
Coronavirus-like particle Covid-19 vaccine	Coronavirus-like particle vaccine (2 dose)	GSK/Medicago	Ph2/3 started Nov 2020 in Canada & US
Covid-19 S-Trimer	Trimerised fusion protein (2 dose)	Clover/Dynavax	Ph2/3 to start H1 2021; interim analysis due mid-2021
Covid-19 vaccine project	Recombinant protein (1 or 2 dose tbc)	Sanofi/Glaxo	Ph3 due to start 2021, pending development of new formulation
INO-4800	DNA vaccine (2 dose)	Inovio	Ph2 stage of pivotal study recruiting; ph3 stage remains on US hold; ph2 enrolling in China
ARCT-021	Self-amplifying mRNA vaccine (1 or 2 dose tbc)	Arcturus	Ph3 planned for Q2 2021 pending data from ongoing Ph2
ZyCoV-D	DNA vaccine (3 doses)	Zydus Cadila	Ph3 cleared to start in India Jan 2021
Note: includes notable projects already progressed into phase II/III development or likely to do so imminently. List not exhaustive. Source: EvaluatePharma & company statements. https://www.evaluate.com/vantage/articles/news/snippets/covid-19-vaccine-pipeline-builds-clover-and-dynavax-push

Roche: SARS-CoV-2 Rapid Antigen Test Nasal allows patient self-collection

  -- The SARS-CoV-2 Rapid Antigen Test Nasal uses a nasal swab to quickly and

      conveniently collect specimens from people suspected of having an active 
      infection 
 
   -- Nasal sampling allows for collection of the sample from the front area of 
      the nose instead of the nasopharynx resulting on a less invasive testing 
      experience for patients 
 
   -- The test also provides patients with the option to self-collect their 
      nasal sample 
 
Roche (SIX: RO, ROG; OTCQX: RHHBY) today 
announced it has obtained the CE mark for its new SARS-CoV-2 Rapid 
Antigen Test Nasal. The test will be available in countries accepting 
the CE mark by mid-February 2021. 
 
 
 
   In comparison to the existing Roche SARS-CoV-2 Rapid Antigen Test, the 
SARS-CoV-2 Rapid Antigen Test Nasal collects the sample from the front 
area of the nose instead of the nasopharynx, resulting in a simplified 
and faster testing procedure(1) . This testing method can help reduce 
overall patient discomfort, particularly in sensitive individuals such 
as children, elderly people and/or people with disabilities. 
 
 
 
   Besides being less invasive, the test also provides patients with the 
option to self-collect their nasal sample under the supervision of a 
healthcare professional. Through reduced physical contact, this method 
of testing can help to decrease the risk of exposure to the virus for 
healthcare professionals. Whether the test could also be used without 
supervision of a healthcare professional will depend on local regulatory 
requirements. 

https://www.marketscreener.com/quote/stock/ROCHE-HOLDING-AG-9364975/news/Press-Release-Roche-announces-the-upcoming-launch-of-the-SARS-CoV-2-Rapid-Antigen-Test-Nasal-allow-32328198/

BioNTech says back on schedule to deliver COVID-19 vaccine doses to EU

 BioNTech and Pfizer Inc are on-track to meet the delivery deadline for their coronavirus vaccine to the European Union, the Germany-based company said on Monday.

European countries are grappling with broad vaccine delays, at least temporarily, as all Western vaccine makers with approved shots - Moderna, Pfizer and partner BioNTech and AstraZeneca - fall behind their initial delivery targets.

BioNTech and Pfizer are working toward ramping up delivery to Europe beginning the week of Feb. 15, the German company said.

Pfizer has successfully modified production processes at its manufacturing plant in Puurs, Belgium, putting the companies back on the original schedule of vaccine dose deliveries to the European Union, BioNTech said.

BioNTech said its own manufacturing site in Marburg, Germany, will be able to start production for validation by the European Medicines Agency in February.

The company also said its European manufacturing network has continued to expand, from three partners in December 2020 when the companies' vaccine was first authorized, to 13 currently.

The companies expect to make 2 billion doses of the vaccine in 2021.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/BioNTech-says-back-on-schedule-to-deliver-COVID-19-vaccine-doses-to-EU-32328412/

Under Biden order, workers refusing unsafe work could stay on unemployment aid

 Many workers called back by employers resuming or expanding operations despite the ongoing coronavirus pandemic face a dilemma: return to jobs that put them at high risk of the virus, or say no, and risk going without pay or unemployment benefits.

President Joe Biden argues workers should not have to make that choice.

An executive order signed on his second full day in office could make it easier for people to still qualify for jobless benefits if they quit or refuse a job that puts them at undue risk of infection from the coronavirus.

More than 18 million Americans are drawing some form of government unemployment assistance.

The order asks the U.S. Department of Labor to clarify that workers who refuse jobs due to unsafe working conditions can still receive unemployment insurance. A department spokesman told Reuters the agency is developing an Unemployment Insurance Program Letter - the usual mechanism for issuing guidelines or clarifying policies - in response to the order.

The Labor Department also issued new guidance on Friday with recommendations on how employers can protect workers from the virus, which has infected more than 25 million Americans and led to more than 433,500 U.S. deaths since the pandemic began.

“In a period where lots of people have lost jobs and people are desperate for work, people will go and end up working under dangerous conditions and they will do so believing they have no other alternative,” said Ken Jacobs, chair of the UC Berkeley Labor Center.

Assuring them they have the right to refuse unsafe work, and paying them enough to afford not to work, is “vitally important,” Jacobs said. “You want people in the greatest risk groups to stay home.”

SEEKING CLARITY

It’s not clear how many workers have lost unemployment benefits after refusing jobs because of COVID-19 safety concerns, said Andrew Stettner, a senior fellow at The Century Foundation and an expert on unemployment insurance. Still, the new guidance should establish minimum protections for workers, replacing an approach that can vary by state, he said.

“It’s been very unclear for a claimant to understand whether they can refuse an offer to go back to work,” Stettner said.

Currently some states, including Texas, publish lists of the circumstances in which a worker might be able to keep receiving benefits after turning down a job. For instance, the state offers exceptions for workers age 65 and up, or those with health conditions that put them at high risk.

But other states advise workers of a narrower set of protections, and many make decisions on a case by case basis.

“The goal would be to have some clear standards,” Stettner said.

The new federal guidance, likely to be issued in the coming weeks, would be aimed at making both states and workers aware they should be able to qualify for unemployment benefits after refusing a job that puts them at greater risk because of their age, a health condition or lack of COVID-19 safety protocols, analysts say.

‘WE NEED A STANDARD’

That policy could make a big difference for people in jobs at restaurants or other businesses requiring workers to be in close proximity to others, two recent studies suggest.

Essential workers were 55% more likely to get infected with coronavirus than those who stayed at home, according to a study of the early months of the pandemic in Pennsylvania published this week by researchers at Independence Blue Cross and the Wharton School of Business.

“We all had a hunch that essential workers by the nature of their jobs are probably more exposed, which means they’re probably more likely to get infected – but what we didn’t know was by how much,” said Wharton’s Hummy Song, one of the paper’s authors.

A separate study out last week from the University of California found deaths of working-age Californians increased by 22% in 2020 from what would have been expected based on prior trends, and the deaths were concentrated in certain occupations.

Deaths among workers in food and agriculture, for instance, were 39% higher. Among healthcare workers, deaths were up 20%, the study noted.

The findings indicate there may be better protections in place in health care settings than in restaurants or other fields, said Yea-Hung Chen, one of the study’s authors.

https://www.reuters.com/article/us-usa-economy-unemployment/under-biden-order-workers-refusing-unsafe-work-could-stay-on-unemployment-aid-idUSKBN2A128L

Facebook Oversight Reverses Hydroxychloroquine Censorship Decision

 Facebook's independent Oversight Board has ruled against the social media giant's decision to remove an October 2020 post touting hydroxychloroquine (HCQ) - the antimalarial which Democrats and their media surrogates were cautiously optimistic about until former President Trump promoted it.

"In October 2020, a user posted a video and accompanying text in French in a public Facebook group related to COVID-19," explained the board on its website. "The post alleged a scandal at the Agence Nationale de Sécurité du Médicament (the French agency responsible for regulating health products), which refused to authorize hydroxychloroquine combined with azithromycin for use against COVID-19, but authorized and promoted remdesivir. The user criticized the lack of a health strategy in France and stated that “[Didier] Raoult’s cure” is being used elsewhere to save lives. The user’s post also questioned what society had to lose by allowing doctors to prescribe in an emergency a “harmless drug” when the first symptoms of COVID-19 appear."

The Oversight Board noted that the user's post did not encourage people to take HCQ without a prescription, and was instead "opposing a governmental policy and aimed to change that policy."

"The combination of medicines that the post claims constitute a cure are not available without a prescription in France and the content does not encourage people to buy or take drugs without a prescription. Considering these and other contextual factors, the Board noted that Facebook had not demonstrated the post would rise to the level of imminent harm, as required by its own rule in the Community Standards," the Board continued, adding that Facebook failed to satisfactorily explain why it removed the post, annd that their 'misinformation and imminent harm rule' is too vague - recommending that the company clarify its standards on health misinformation.

"The Board also found Facebook's misinformation and imminent harm rule, which this post is said to have violated, to be inappropriately vague and inconsistent with international human rights standards," wrote the panel. "A patchwork of policies found on different parts of Facebook's website make it difficult for users to understand what content is prohibited. Changes to Facebook's COVID-19 policies announced in the company's Newsroom have not always been reflected in its Community Standards, while some of these changes even appear to contradict them."

One can't help but wonder how many lives the left's politicization of HCQ may have cost, after several studies have concluded that when taken early into a COVID-19 infection, the antimalarial has been shown to reduce mortality.

The currently completed retrospective studies and randomized trials have generally shown these findings: 1) when started late in the hospital course and for short durations of time, antimalarials appear to be ineffective, 2) when started earlier in the hospital course, for progressively longer durations and in outpatients, antimalarials may reduce the progression of disease, prevent hospitalization, and are associated with reduced mortality. -American Journal of Medicine

One Brazilian study found 4.6x fewer hospitalizations in patients who took HCQ and azithromycin within seven days of infection, while a retrospective study of cases in Detroit showed a 71% reduction in mortality with early treatment using the HCQ / Azithromycin combination.

 

A meta-analysis of 105,040 cases from 20 studies in 9 countries found a reduction in mortality by up to three times in groups treated early with Hydroxychloroquine and Azithromycin.

 

Unfortunately for those hoping to use HCQ, Trump made the mistake of endorsing it, setting off a cascade of anti-HCQ propaganda which has been largely disproven.

https://www.zerohedge.com/covid-19/facebook-oversight-reverses-hydroxychloroquine-censorship-decision

Concert misses primary endpoint in schizophrenia trial

 CTP-692 Did Not Achieve Primary Endpoint Assessing Positive and Negative Syndrome Scale (PANSS) Total Score at 12 Weeks

Concert Pharmaceuticals, Inc. (NASDAQ:CNCE) today announced that its Phase 2 clinical trial to evaluate CTP-692 as an adjunctive treatment in patients with schizophrenia did not meet the primary endpoint or other secondary endpoints. CTP-692 is a deuterated form of D-serine, an endogenous amino acid that is a co-agonist of the NMDA receptor.

"The body of evidence in the field supporting D-serine as an adjunctive treatment for schizophrenia was compelling and led us to advance CTP-692 into a Phase 2 proof of concept study. Unfortunately, we didn’t see the results we hoped for to support continuation of this program. Going forward, we will focus our internal resources on the advancement of CTP-543, which is currently in Phase 3 evaluation for the treatment of alopecia areata, and evaluation of additional pipeline candidates," stated Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals. "We believe that we conducted a well-designed, well-controlled study and extend our gratitude to the patients, caregivers and investigators for their participation in the CTP-692 Phase 2 study. It’s our hope that these learnings will support future research to address the important need to improve the symptom domains of schizophrenia."

https://finance.yahoo.com/news/concert-pharmaceuticals-announces-results-ctp-120000293.html