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Tuesday, May 31, 2022

Canada OKs Drug Decriminalization Test in British Columbia

 Canada’s government said Tuesday it will allow British Columbia to try a three-year experiment in decriminalizing possession of small amounts of drugs, seeking to stem a record number of overdose deaths by easing fear of arrest by users in need of help.

The policy approved by federal officials doesn’t legalize the substances, but Canadians in the Pacific coast province who possess up to 2.5 grams of illicit drugs for personal use will not be arrested or charged.

The three-year exemption taking effect Jan. 31 will apply to drug users 18 and over and include opioids, cocaine, methamphetamine and MDMA, also known as ecstasy.

“Stigma and fear of criminalization cause some people to hide their drug use, use alone, or use in other ways that increase the risk of harm. This is why the Government of Canada treats substance use as a health issue, not a criminal one,” tweeted Dr. Theresa Tam, Canada’s chief public health officer.

The province’s health officer, Dr. Bonnie Henry, said that “we are taking an important step forward to removing that fear and shame and stigma.”

“This is not one single thing that will reverse this crisis but it will make a difference,” she added.

Dana Larsen, a drug policy reform activist, called the announcement “a step in the right direction,” but said he would prefer to see development of a safe drug supply.

“It’s not going to stop anybody dying of an overdose or drug poisoning,” Larsen said. “The drugs are still going to be contaminated.”

“I think we need stores where you can go in and find legal heroin, legal cocaine and legal ecstasy and things like that for adults,” he said. “The real solution to this problem is to treat it like alcohol and tobacco.”

Alissa Greer, an assistant professor at Simon Fraser University who has a doctorate in public health, said a regulated decriminalization of drugs could help lessen overdose deaths.

She said it would be good for users to be able to obtain drugs from "a regulated supply through various models, whether that’s a prescription model, a pharmacy model, more of a compassion club model ... rather than going down to 7-Eleven and buying heroin.”

British Columbia is the first Canadian province to apply for an exemption from Canada’s drug laws.

In 2001, Portugal became the first country in the world to decriminalize the consumption of all drugs. People caught with less than a 10-day supply of any drug are usually sent to a local commission, consisting of a doctor, lawyer and social worker, where they learn about treatment and available medical services.

In 2020, Oregon voted to become the first U.S. state to decriminalize hard drugs. Under the change, possession of controlled substances is a newly created Class E “violation,” instead of a felony or misdemeanor. It carries a maximum $100 fine, which can be waived if the person calls a hotline for a health assessment. The call can lead to addiction counseling and other services.

Carolyn Bennett, federal minister of mental health and addictions, said the experiment in British Columbia could serve as a template for other jurisdictions in Canada.

“This time-limited exemption is the first of its kind in Canada,” she said. “Real-time adjustments will be made upon receiving analysis of any data that indicates a need to change.”

Since 2016, there have been over 9,400 deaths due to toxic illicit drugs in British Columbia, with a one-year record of 2,224 in 2021.

Vancouver Mayor Kennedy Stewart said he gets emails every Monday on drug deaths, including nine last week and 12 the week before. He said one week it was his own family member.

“I felt like crying, and I still feel like crying. This is a big, big thing,” Stewart said.

The 2.5-gram limit set by federal officials for the experiment falls short of the 4.5 grams requested by British Columbia. The higher amount already had been called too low a threshold by some drug-user groups that have said the province didn't adequately consult them.

Sheila Malcolmson, British Columbia’s minister of mental health, said fear of being criminalized has led many people to hide their addiction and use drugs alone.

“Using alone can mean dying alone, particularly in this climate of tragically increased illicit drug toxicity,” Malcolmson said.

She said the coroner in British Columbia reports that between five and seven people die a day in the province from overdoses and that half of those happen in a private home, often when people are alone.

With $600M in Funding, Ultima is Removing Cost Barriers to Genomic Research

 How much could a human genome cost? The answer is $100, according to newly unveiled biotech company Ultima Genomics.

Ultima launched on Tuesday with $600M in financing which could theoretically be used to buy six million of its $100 human genomes. The company was born to remove the traditionally costly price of genomic information that researchers and clinicians have been subject to and provide a solution to such financial barriers.

"Scientists and clinicians continuously make tradeoffs between the breadth, depth and frequency of genomic information they collect," Doron Lipson, chief scientific officer of Ultima Genomics said in a press release. "By overcoming the limitations of conventional next-generation sequencing technologies, researchers can now design experiments and clinical assays that were previously impossible."

Ultima has achieved this affordable human genome by utilizing several technological advances. The company uses an open substrate, which creates a low-cost reaction surface that delivers billions of genetic reads while avoiding costly flow cells and complicated fluidics. Ultima also boasts “novel scalable chemistry”, which combines the speed, efficiency and read lengths of natural nucleotides with the accuracy and scalability of endpoint detection, revolutionary sequencing hardware and machine learning capabilities.

Ultima has already demonstrated its platform’s efficacy in several publications and projects. For example, researchers at The Whitehead Institute demonstrated the immediate usability of the platform in large-scale single-cell studies. Additionally, researchers at Stanford University’s Center for Genomics and Personalized Medicine (SCGPM) used Ultima’s technology to conduct a whole-genome methylation landscape of pre-cancerous tissues.

"Ultima Genomics' architecture will revolutionize sequencing and take what we can do to a whole new level," Michael Snyder, director of SCGPM said.  "The ability to sequence many thousands of genomes and epigenomes will transform diagnostics and disease risk prediction."

Ultima’s platform has come to fruition after five years of building the sequencing architecture which includes novel approaches to flow cell engineering, sequencing chemistry and machine learning. The technology’s ability to scale far beyond current conventional measures primes it for proliferative use in research and diagnostic settings.

"DNA is nature's storage media and the instruction set for every living organism, yet with current technologies, we can't access that information at the scale needed to truly understand complex biology," Gilad Almogy, Ultima Genomics founder and CEO said in a statement. "Our architecture is intended for radical scaling, and the $100 genome is merely the first example of what it can deliver. We are committed to continuously drive down the cost of genomic information until it is routinely used in every part of the healthcare system."

This objective will surely be welcomed with open arms in healthcare. According to MedlinePlus, the cost of genetic testing can range from under $100 to more than $2,000 for just one test, and multiple tests of one individual or an individual’s family may be warranted for a meaningful result. For people with some types of cancer, including breast cancer, genetic counseling and testing may be sought out to determine risk and preventative steps, but high financial barriers can deter someone from seeking out these preventative appointments.

 General Atlantic, Andreessen Horowitz, D1 Capital and Khosla Ventures, among others, contributed to the financing round.

Australia in talks with U.S. to supply infant formula


Australia is in talks with the United States to supply baby food, an Australian government spokesperson said on Wednesday, after the apex U.S. health regulator relaxed its import policy to address a nationwide shortage.

Makers of baby food globally are exploring opportunities of supplying to the U.S. after the easing of import norms. Two million cans of formula from the UK are headed to American shores, while Bubs Australia struck a deal with the U.S. Food and Drug Administration (FDA) last week to supply 1.25 million cans.

Several dairy firms in Australia and New Zealand, including the world's biggest dairy exporter Fonterra, were also in similar discussions with the FDA, Reuters reported on Monday.

"The Australian government will continue to work with the Biden Administration to confirm regulatory arrangements and facilitate exports of infant formula," a spokesperson for Australia's Department of Agriculture, Water and the Environment, said in an emailed statement.

"Australian Government agencies have been actively engaging with the Australian infant formula industry to help secure supply of infant formula to the U.S."

The agency didn't provide additional details on the extent of talks with the U.S. government.

Meanwhile, a spokesperson for New Zealand's Ministry of Primary Industry said the country was "in a good position" to supply to the U.S. market and help them tackle the shortage.

He added that the decision to ship baby food to the U.S. rested exclusively with the manufacturers.

Diabetes may weaken teeth and promote tooth decay

 People with both Type 1 and Type 2 diabetes are prone to tooth decay, and a new study from Rutgers may explain why: reduced strength and durability of enamel and dentin, the hard substance under enamel that gives structure to teeth.

Researchers induced Type 1 diabetes in 35 mice and used a Vickers microhardness tester to compare their teeth with those of 35 healthy controls over 28 weeks. Although the two groups started with comparable teeth, enamel grew significantly softer in the diabetic mice after 12 weeks, and the gap continued to widen throughout the study. Significant differences in dentin microhardness arose by week 28.

"We've long seen elevated rates of cavity formation and tooth loss in patients with diabetes, and we've long known that treatments such as fillings do not last as long in such patients, but we did not know exactly why," said Mohammad Ali Saghiri, an assistant professor of restorative dentistry at the Rutgers School of Dental Medicine.

The study advances a multiyear effort by Saghiri and other researchers to understand how diabetes affects dental health and to develop treatments that counter its negative impact. Previous studies have established that people with both types of diabetes have significantly elevated rates of most oral health issues, both in the teeth and the soft tissues that surround them. Saghiri and other researchers also have demonstrated that diabetes can interfere with the ongoing process of adding minerals to teeth as they wear away from normal usage.

"This is a particular focus of mine because the population of people with diabetes continues to grow rapidly," Saghiri said. "There is a great need for treatments that will allow patients to keep their teeth healthy, but it has not been a major area for research."

Story Source:

Materials provided by Rutgers University. Original written by Andrew Smith. Note: Content may be edited for style and length.

Journal Reference:

  1. Mohammad Ali Saghiri, Nader Sheibani, Toshihisa Kawai, Devyani Nath, Sahar Dadvand, Saeid B. Amini, Julia Vakhnovetsky, Steven M. Morgano. Diabetes negatively affects tooth enamel and dentine microhardness: An in-vivo studyArchives of Oral Biology, 2022; 139: 105434 DOI: 10.1016/j.archoralbio.2022.105434

Novel cellular process can aid understanding of aging-related diseases

 The study of autophagy -- the recycling and repair process within cells -- has huge potential to aid in fighting the ageing process, bacterial and viral infections and diseases including cancer, Alzheimer's and Parkinson's.

A team of researchers led by Professor Ioannis Nezis from the School of Life Sciences at the University of Warwick, has identified the molecular and cellular mechanisms that regulate selective autophagy in the fruit fly Drosophila melanogaster.

While the function of these processes is increasingly understood in mammals this is one of the first studies in insects.

The study opens new avenues in our understanding of the regulation of Golgi complex turnover by selective autophagy.The Golgi complex is a stack of flat sacs formed by membranes inside the cell. It prepares proteins and fat molecules for transportation and use in other places inside and outside the cell.

Professor Nezis and his team used gene editing, confocal and electron microscopy to identify a novel type of selective autophagy, termed Golgiphagy, meaning how cells degrade a cell organelle called Golgi complex by autophagy.

In the paper, 'GMAP is an Atg8a-inteacting protein that regulates Golgi turnover in Drosophila' published today in the journal Cell Reports, PhD students Ashrafur Rahman, Raksha Gohel and colleagues describe how gene editing was used to create fruit flies unable to process specific proteins by autophagy.

Comparison of the gene edited flies with their wild type counterparts showed:-

  • That Atg8a's LDS docking site is important in the execution of selective autophagy
  • That selective autophagy regulates the size and morphology of the Golgi apparatus
  • That the GMAP (Golgi microtubule-associated protein) protein interacts with Atg8a and the LIR motif at position 320-325 is important for this interaction
  • That GMAP's LIR motif is important Golgiphagy

Lead author of the research Professor Ioannis Nezis from the School of Life Sciences at the University of Warwick, said:

"Understanding the molecular mechanisms of selective autophagy of Golgi complex in cells will help open new avenues of research that will assist elucidating the underlying cellular mechanisms of diseases."

Story Source:

Materials provided by University of WarwickNote: Content may be edited for style and length.

Journal Reference:

  1. Ashrafur Rahman, Peter Lőrincz, Raksha Gohel, Anikó Nagy, Gábor Csordás, Yan Zhang, Gábor Juhász, Ioannis P. Nezis. GMAP is an Atg8a-interacting protein that regulates Golgi turnover in DrosophilaCell Reports, 2022; 39 (9): 110903 DOI: 10.1016/j.celrep.2022.110903

Chinese Media And Influencers Blame US For Spread Of Monkeypox

 by Alex Wu via The Epoch Times (emphasis ours),

With the outbreak of monkeypox, Chinese state media and social media influencers in China have claimed that the monkeypox virus originated in a U.S. laboratory. They have also made claims that monkeypox will cause the next pandemic, despite European and American scientists pointing out that the possibility of a pandemic is extremely small due to the close contact needed to transmit the virus.

They have also said that, at present, patients are infected with a natural monkeypox virus with no links to a laboratory.

“Jimu News,” a subsidiary of state-run Hubei Daily Group, published an article on May 23 implying that escaped monkeys from a truck involved in a traffic accident on Jan. 21 in Pennsylvania have something to do with the recent monkeypox outbreak in the United States and Europe.

The four monkeys that escaped, among the 100 being transported by the truck, were recaptured next day.

The first confirmed case of monkeypox in the United States appeared in Massachusetts on May 18. The patient was diagnosed after returning to the United States from Canada. Cases have since appeared in New York City, Florida, and Utah.

Meanwhile, Chinese social media influencers who are supportive of China’s ruling communist regime have echoed claims similar to those made by official state media outlets.

On May 20, a blogger named “Guyan Muchan” posted a few screenshots on Chinese social media Weibo of a document claiming that to be a “monkeypox biochemical pandemic plan leaked by the United States,” implying that the U.S. government was aware of the outbreak in advance.

“Guyan Muchan” has 6.41 million followers on Weibo, and the post has been liked by more than 7,500 users and received more than 660 comments. Influenced by this post, someone even commented that the United States is “evil beyond human imagination.”

The document was actually from a hypothetical biohazard scenario published in a research report by the U.S. think tank Nuclear Threat Initiative in 2021. The document is available for viewing on its website.

Major international media, such as Reuters and Bloomberg, further pointed out that: “Pandemic preparedness scenarios and symposiums are not proof that pandemics are planned, nor are these scenarios a new occurrence.”

After the false claim is debunked, “Guyan Muchan” has continued to spread similar claims blaming the U.S. for the spread of the monkeypox.

A self-proclaimed “patriotic” cartoonist “Sweet Potato Bear Lao Liu” also posted claims that the spread of the monkeypox virus was related to a U.S. laboratory. On May 21, he posted on his Weibo account that the United States may have modified and upgraded the monkeypox virus to develop a more virulent and transmissible variant, to lead to the next pandemic.

Zhao Shengye, an internet technology blogger, further claimed on his Weibo account that, after researching the monkeypox virus that appeared in Europe and the United States, he believes the probability of the monkeypox being produced in a laboratory through virus gain-of-function research was greater than 99.9 percent. Zhao has 4 million Weibo followers.

A major mainland Chinese news portal NetEase News published an article on May 23, titled “Is the Monkeypox Virus Man-made? The United States wrote the data on the outbreak of monkeypox last year, which is terrible.” The article claims that monkeypox has more than 50 mutations, which exceeds the mutation rate of the Chinese Communist Party (CCP) virus that caused COVID-19. It added that no viral evolution in nature would have such a fast mutation rate.

Such claims have been refuted by international scientists.

David Robertson, head of viral genomics and bioinformatics at the University of Glasgow, told the Newsweek that the claims are baseless as “there’s no evidence for monkeypox being generated in a lab.”

Richard Ebright, professor of chemistry and chemical biology at Rutgers University in New Jersey, echoed the point, “All indications are that the monkeypox outbreak involves a natural monkeypox virus.”

Daniel Bausch, an infectious disease expert and president of the American Society of Tropical Medicine & Hygiene, told Axios that the risk of a monkeypox pandemic is extremely low.

“I don’t think there’s a reason for panic, I don’t think we’re going to have tens of thousands of cases,” he said of the virus.

According to the Massachusetts Department of Public Health, monkeypox is not known to spread easily between people, requiring direct contact with bodily fluids, lesion fluids, or prolonged face-to-face contact.

Biotech Investors: Mark Your Calendar For These June PDUFA Dates

 May turned out to be a month of mixed fortunes as far as regulatory reviews are concerned. New molecular entity approvals, an indicator of innovation in drug research, totaled three during the month, bringing the total for the year to 15. This compares to the 24 NMEs the Food and Drug Administration approved by May 2021.

Among the companies that received the FDA's greenlight were Phathom Pharmaceuticals, Inc. 

Bristol-Myers Squibb Company  and Novartis AG .

On the other hand, Verrica Pharmaceuticals Inc.'s 

 viral skin infection treatment candidate was rejected by the regulator for the third time. Amid the adverse ruling, the stock lost about three-quarters of its value. The FDA extended the review periods of Pfizer, Inc. -Myovant Sciences, Inc.  combo's application to expand the label of Myfembree and Amicus Therapeutics, Inc.'s  Pome disease application.

Here are the key regulatory decisions scheduled for June:

Acer-Relief Await Nod For Urea Cycle Disorder Treatment

Company: Acer Therapeutics, Inc. 

 & Relief Therapeutics Holding AG 

Type of Application: new drug application (NDA)
Candidate: ACER-001 (sodium phenylbutyrate)
Indication: urea cycle disorders
Date: June 5

The two companies are seeking approval for ACER-001 under the 505(b)(2) pathway, which allows manufacturers to apply for approval without having to repeat all the drug development work done for an innovator drug.

UCDs are a group of disorders caused by genetic mutations that result in deficiency of one of the six enzymes that catalyze the urea cycle. This can lead to an excess accumulation of ammonia in the bloodstream. Acute hyperammonemia can cause lethargy, somnolence, coma, and multi-organ failure, while chronic hyperammonemia can lead to headaches, confusion, lethargy, failure to thrive, behavioral changes, and learning and cognitive deficits.

Current medical treatments for patients with UCDs include Horizon Therapeutics plc.'s 

 Ravicti and Buphenyl. Acer noted that there have been reports of non-compliance associated with available medications due to unpleasant taste, frequency with which medication must be taken, required number of pills, and the high cost of the medication.

Can Regeneron-Sanofi's Dupixent Snag Another Nod

Company: Regeneron Pharmaceuticals, Inc. 

 & Sanofi 
Type of Application: supplemental biologic license application (sBLA)
Candidate: Dupixent
Indication: atopic dermatitis
Date: June 8

The FDA accepted the sBLA for priority review on Feb. 10, with the application seeking approval of the combo's inflammatory disease drug as an add-on maintenance treatment for children, aged 6 months to 5 years, with moderate-to-severe atopic dermatitis.

Atopic dermatitis is a chronic type 2 inflammatory skin disease, and 85%-90% of patients develop symptoms before 5 years of age, which can often continue through adulthood. Current treatment options in this age group are primarily topical steroids, which can be associated with safety risks and may impair growth when used long-term.

Rhythm Strives to Score Another Approval For Obesity Drug

Company: Rhythm Pharmaceuticals, Inc. 

Type of Application: supplemental NDA
Candidate: Imcivree (setmelanotide)
Indication: Bardet-Biedl syndrome or Alström syndrome
Date: June 16

Rhythm, which develops treatments for rare genetic diseases of obesity, has an FDA decision date of June 16 for its Imcivree, which is being evaluated as a treatment option for obesity and the control of hunger in adult and pediatric patients 6 years of age and older with BBS or Alström syndrome.

The original PDUFA date of March 16 was extended by three months, as the FDA needed additional time to review clinical efficacy data submitted by the company upon the agency's request to conduct additional subgroup analyses.

Can Bristol-Myers Squibb's Blood Cancer Therapy Get Label Expansion?

Company: Bristol-Myers Squibb
Type of Application: sBLA
Candidate: Breyanzi (lisocabtagene maraleucel)
Indication: large B-cell lymphoma
Date: June 24

Breyanzi is a CAR T cell therapy that has already been approved for treating patients with relapsed or refractory large B-cell lymphoma, a type of blood cancer, after two or more lines of systemic therapy. Bristol-Myers Squibb's application for label expansion seeks approval of the cell therapy for large B-cell lymphoma patients following a failed first-line therapy.

The standard-of-care currently is salvage chemotherapy followed by a high-dose chemotherapy, plus an autologous stem cell transplant. The company now thinks Breyanzi has the potential to be a new standard-of-care.

Bristol-Myers Squibb-Merk Expect Smooth Sailing For Reblozyl Following Extended Review Period

Company: Bristol-Myers Squibb & Merck & Company, Inc. 

Type of Application: sBLA
Candidate: Reblozyl (luspatercept)
Indication: anemia in adults with non-transfusion dependent beta thalassemia
Date: June 27

Reblozyl is an erythroid maturation agent that promotes late-stage red blood cell maturation in animal models. It's being jointly developed by Bristol-Myers Squibb and Merck in the U.S. Merck received rights to the treatment through its acquisition of Acceleron. The FDA had extended the original review period of March 27 by three months.

Spero's Lead Drug May Not Receive Approval Due to Data Insufficiency

Company: Spero Therapeutics, Inc. 

Type of Application: NDA
Candidate: tebipenem HBr oral tablets
Indication: complicated urinary tract infections (cUTI)
Date: June 27

Tebipenem HBr is Spero's lead product candidate that is being developed as the first oral carbapenem antibiotic for use in cUTI, including pyelonephritis.

Spero said in early May that its discussions with the FDA suggested that the data package may be insufficient to support approval during this review cycle. Following the development, the company announced a reduction in its workforce by approximately 75% and a restructuring of its operations to reduce operating costs and reallocate resources towards the clinical development programs of SPR720 and SPR206.

Is Amylyx In For Disappointment With Its ALS Drug?

Company: Amylyx Pharmaceuticals, Inc. 

Type of Application: NDA
Candidate: AMX0035
Indication: amyotrophic lateral sclerosis (ALS)
Date: June 29

FDA's Peripheral and Central Nervous System Drugs Advisory Committee, which met in late March to discuss the NDA, voted that the submitted Phase 2 data do not support the efficacy of the drug in treating ALS.

Adcom Calendar

FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) is scheduled to meet on June 7 to discuss Novavax, Inc.'s 

 emergency use authorization (EUA) request for its vaccine to prevent COVID-19 in individuals 18 years of age and older.

The Cellular, Tissue, and Gene Therapies Advisory Committee will deliberate on bluebird bio, Inc.'s 

 two BLAs for gene therapy candidates elivaldogene autotemcel and betibeglogene autotemcel. The former is being evaluated for the treatment of patients less than 18 years of age with early cerebral adrenoleukodystrophy and the latter for treating patients with β-thalassemia who require regular red blood cell transfusions.

The Adcom is scheduled to meet for two days – on June 9, between 10 am ET and 6 pm ET, and on June 10, between 10 am ET and 4 pm ET.

The VRBPAC will meet again on June 14 and 15 to discuss expanding the EUA accorded to the COVID-19 vaccines of Moderna, Inc. 

 and Pfizer, Inc. -BioNTech SE . On June 14, the committee will discuss authorization of the primary series of Moderna's vaccine for children and adolescents, six years through 17 years.
The very next day, the committee will review the application for expanding the authorizations of the vaccines of both Moderna and Pfizer-BioNTech for infants and children, six months through four years of age.

On June 17, the Psychopharmacologic Drugs Advisory Committee will discuss sNDAs for Nuplazid tablets, submitted by Acadia Pharmaceuticals Inc. 

, for the proposed treatment of hallucinations and delusions associated with Alzheimer's disease psychosis. Incidentally, Nuplazid was rejected by the FDA for the same indication in April 2021.