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Sunday, June 21, 2020

Breakthrough discovery to transform prostate cancer treatment

A novel formulation of the prostate cancer drug abiraterone acetate – currently marketed as Zytiga – will dramatically improve the quality of life for people suffering from prostate cancer, as pre-clinical trials by the University of South Australia show the new formulation improves the drug’s effectiveness by 40 per cent.
Developed by Professor Clive Prestidge’s Nanostructure and Drug Delivery research group at UniSA’s Cancer Research Institute, the breakthrough discovery uses an oil-based oral formulation that not only enables a smaller dose of the drug to be effective, but also has the potential to dramatically reduce possible side effects, such as joint swelling and diarrhoea.
Despite Zytiga being the leading formulation to treat prostate cancer, lead researcher, Dr Hayley Schultz says the new formulation will ultimately provide a better treatment for patients with prostate cancer.
Prostate cancer is the most commonly diagnosed cancer in men, with one in six at risk of diagnosis before the age of 85. In 2019, more than 19,500 cases of prostate cancer were diagnosed in Australia. Globally, prostate cancer cases reached 1.28 million in 2018.
“Many drugs are poorly water soluble, so when they’re ingested, they enter the gut but don’t dissolve, which means that their therapeutic effect is limited,” Dr Schultz says.
“This is the case for Zytiga. Here, only 10 per cent of the dose is absorbed, leaving the other 90 per cent undissolved, where it simply passes through the body as waste.
“On top of this, patients taking Zytiga must fast for two hours prior to taking the drug, and another hour after taking the drug to achieve predictable absorption. And as you can imagine, this can be painstakingly inconvenient.
“Our new formulation changes this. By using oils to mimic pharmaceutical food effects, we’re able to significantly increase the drug’s solubilisation and absorption, making it more effective and a far less invasive treatment for patients.”
The new formulation uses very high levels of abiraterone acetate dissolved within a specific oil and encapsulated within porous silica microparticles to form a powder that can be made into tablets or filled into capsules. Applied to human treatment, it could reduce the dose from 1000mg to 700mg per day, without the need for fasting.
Prof Prestidge says if the team can secure funding, clinical trials in humans could be just two years away.
“Based on our knowledge of this drug’s pharmaceutical food effect, we hypothesise its absorption in humans will be extensively improved using this technology”, Prof Prestidge says.
“Anything we can do to contribute to the development of a commercialised product to improve the lives of patients, is invaluable.
“This novel formulation is flexible enough to be adopted by thousands of different medicines; its potential to help patients of all kinds is exponential.”
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* This research – Enhancement of abiraterone acetate oral bioavailability by supersaturated silica lipid hybrids – is published in the International Journal of Pharmaceutics, available here: https://www.sciencedirect.com/science/article/pii/S0378517320302489
https://www.eurekalert.org/pub_releases/2020-06/uosa-bdt061920.php

Regeneron, Sanofi Dupixent Single-Dose Pen Approved By FDA

Regeneron Pharmaceuticals Inc. and Sanofi said Friday the U.S. Food and Drug Administration has approved a 300-mg single-dose pre-filled pen for Dupixent dupilumab.
The companies said the pre-filled pen is approved for all Dupixent indications in patients aged 12 years and older, which includes use in certain patients with atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis, for at-home administration.
The companies said the 300-mg pre-filled pen is expected to be available in the U.S. in the third quarter of 2020. The pre-filled pen features a hidden needle and single-press auto-injection, along with visual and audio feedback to help with administration.
Regeneron and Sanofi are working with the FDA to provide additional data they require to complete their review of the 200-mg pre-filled pen. The pre-filled syringe continues to be available in both 200 mg and 300 mg doses for use in a clinic or at home by self-administration.

https://www.marketscreener.com/REGENERON-PHARMACEUTICALS-10649/news/Regeneron-Pharmaceuticals-Sanofi-Dupixent-Single-Dose-Pen-Approved-By-FDA-30797071/

Efforts for Coronavirus Vaccine Focus on Vulnerable Group: Older Adults

Health experts are worried about whether coronavirus vaccines under development will adequately protect the elderly, sparking efforts to make sure there are shots that can help the vulnerable group.
Older adults are especially susceptible to infection by the virus, and at higher risk of falling critically ill and dying, at least partly because their immune systems have lost strength with age. Public-health officials and scientists are concerned that a weakened immune system could also limit the effectiveness of a coronavirus vaccine, just as it has sapped the power of other shots in older people.
“It would not be particularly encouraging if we have a vaccine that’s capable of protecting 20-year-olds who probably have a pretty low risk anyway of getting sick, and doesn’t work at all for people over 65,” Francis Collins, director of the National Institutes of Health, said in an interview.
To find a vaccine that works safely in older adults, researchers at Pfizer Inc. and other companies are exploring possible options such as increasing the doses or adding a booster to the shot. At least one vaccine specifically for the elderly is in development. And Pfizer, the University of Oxford and others have started testing their coronavirus vaccine candidates in older adults.
Some of the experimental vaccines “may turn out to be better for older individuals, and that’ll be a big issue in terms of how we then end up deploying these,” Dr. Collins said.
Older adults have been especially hard hit by the new coronavirus. Between March and mid-June, Americans over the age of 65 had the highest rate of hospitalization among all age groups, about double the rate for people 50 to 64 years old and five times the rate for 18- to 49-year-olds, according to the Centers for Disease Control and Prevention.
Vaccines will be crucial, public-health experts say, to stopping the spread of the virus. More than 100 are in development and more than a dozen are in human testing, according to the World Health Organization.
The shots work by tricking the body into thinking it has been infected with a virus, prompting the immune system to make antibodies to fight the pathogen. Yet antibody production weakens over time, part of a process known as immunosenescence. Researchers aren’t sure why, aside from the fact that the body generally weakens with age.
The loss of immune system strength makes older adults more susceptible to bacterial and viral infections such as influenza. Some 90% of flu deaths in the U.S. each year are of people over the age of 65.
And flu vaccines tend not to protect older adults as well as they defend younger people. Research shows the vaccines protect between 70% and 90% of children and younger adults, but 30% to 50% of adults over 65.
“We’re just starting to understand some of the ways to overcome those immune responses,” said Dr. Kawsar Talaat, deputy director of clinical research for the Institute for Vaccine Safety at the Johns Hopkins Bloomberg School of Public Health, who is slated to help coronavirus vaccine developers test their shots in older adults. “We hadn’t been designing vaccines for the elderly for a long time.”
The Food and Drug Administration is working with companies to make it easier for experimental vaccines to be tested in older adults earlier during clinical trials, and alongside younger subjects, an agency spokesman said. Moderna Inc. is among the companies already testing its experimental shot in adults older than 55, while Johnson & Johnson plans to after it begins testing next month.
Pfizer, which is also testing its potential coronavirus vaccines in older people, is studying whether increasing the dosage could protect the elderly better. Higher doses have helped make flu vaccines more effective in the elderly.
Researchers at the New York drugmaker are also curious whether their gene-based technology might prove more effective in elderly people than shots based on older, different technologies, said Kathrin Jansen, Pfizer’s head of vaccine research and development.
The unproven technology uses messenger RNA, or mRNA, programmed to tell cells to make proteins that can protect against the coronavirus. Pfizer wants to see whether the synthesized mRNA spurs both a broad immune response, which may not be as strong in older adults, as well as a targeted response that makes up for the gap, Dr. Jansen said.
The more powerful punch could “help overcome the difference between younger adults’ responses and that of an older adult,” Dr. Jansen said in an interview.
Some companies are considering the use of a booster, or adjuvant, to strengthen a vaccine’s effect on the immune systems of older adults. An adjuvant in Shingrix, a shingles vaccine from GlaxoSmithKline PLC, helps the shot safely reduce the risk of contracting the disease by more than 90% in older people, almost twice the percentage of the other shingles vaccine in the U.S., according to the CDC.
Glaxo provided one of its adjuvants to Sanofi SA and six other drugmakers working on coronavirus vaccines, said Dr. Thomas Breuer, chief medical officer of GSK vaccines. Glaxo had used that adjuvant in an H1N1 vaccine.
Meantime, researchers at Boston Children’s Hospital are trying to develop a vaccine specifically for older adults. The researchers are screening vaccine candidates against white blood cells donated by older people to see whether any of the shots would work better in the elderly, said Ofer Levy, director of the hospital’s vaccines program.
The hospital researchers have narrowed the search to about seven different vaccine candidates, and are also evaluating about 50 potential adjuvants that could be added, Dr. Levy said. They hope to begin testing a vaccine in people ages 65 and older next year, he said.

https://www.marketscreener.com/MODERNA-INC-47437573/news/Efforts-for-Coronavirus-Vaccine-Focus-on-Vulnerable-Group-Older-Adults-30802928/

Chinese launch phase-2 human test for possible coronavirus vaccine

Chinese researchers have started a second phase human trial of a possible coronavirus vaccine, the Institute of Medical Biology at Chinese Academy of Medical Sciences (IMBCAMS) said on Sunday, in efforts to further assess effectiveness and safety.
About a dozen vaccines are in different stages of human tests globally, as the World Health Organization warns the coronavirus pandemic is accelerating and “the world is in a new and dangerous phase”.
However, none of the vaccine trials have passed large-scale, late-stage phase 3 clinical trials, a necessary step before getting regulatory approval for sale.
IMBCAMS began on Saturday a phase 2 human test for its experimental shot, which is among six possible vaccines Chinese scientists are testing in humans, following an on-going phase-1 study that has recruited about 200 participants since May, the institute said on Sunday in its social media channel.

The phase-2 trial will determine the shot’s dose and continue to evaluate whether the potential vaccine can safely trigger immune responses in healthy people.

IMBCAMS said it expects to use a plant dedicated to producing a coronavirus vaccine this year to prepare for China’s future vaccine supplies.
As early as by the end of 2020, certain groups of people with special needs can use experimental vaccines under urgent circumstances, Gao Fu, director at the Chinese Center for Disease Control and Prevention, said last month.
The coronavirus, which was first detected in China late in 2019, has infected 8.81 million people globally and killed more than 460,000 people.
https://www.reuters.com/article/us-health-coronavirus-china-vaccine/chinese-researchers-launch-phase-2-human-test-for-possible-coronavirus-vaccine-idUSKBN23S08H

India gives Hetero Labs approval to make Gilead’s COVID-19 drug

India’s drug regulator has given Hetero Labs the green light to manufacture and market its generic version of Gilead Science’s experimental COVID-19 treatment remdesivir, the Indian pharmaceutical company said on Sunday.
The drug, which will be marketed under the brand name Covifor, will likely be priced at 5,000 to 6,000 rupees ($66-$79) for a 100 milligram dose, Hetero said.
India’s Cipla Ltd (CIPL.NS) has also received approval from the Drug Controller General of India (DGCI) to manufacture and market the drug, according to a report bit.ly/2AVcs0y in Indian Express.
Cipla and DGCI were not immediately available for comment.

Gilead Sciences Inc (GILD.O) signed non-exclusive licensing pacts last month with five generic drugmakers based in India and Pakistan to expand the supply of its COVID-19 treatment.
The pacts allow Jubilant Life Sciences Ltd (JULS.NS), Cipla, Hetero Labs, Mylan NV (MYL.O) and Ferozsons Laboratories Ltd FERO.PSX to make and sell the drug in 127 countries.
https://www.reuters.com/article/us-health-coronavirus-india-remdesivir/india-gives-hetero-labs-approval-to-make-gileads-covid-19-drug-idUSKBN23S0EO

Spain reopens its borders as state of emergency comes to an end

Passengers wearing masks and wheeling suitcases arrived at Madrid’s main airport and French people crossed the border to buy bargain alcohol and tobacco on Sunday as Spain opened its borders to most European countries and ended a state of emergency imposed to contain COVID-19.
Spain’s borders are now open to all European Union countries except Portugal, as well as Schengen area members outside the bloc and Britain in a much-needed boost to the country’s tourism industry which accounts for more than 12% of the economy.
British tourists will be allowed in without having to quarantine, Spain said on Saturday, even though they will still be subject to 14 days isolation upon their return..
Spaniards were also allowed to move freely around the country from Sunday and many were expected to visit friends, relatives and second homes in other regions. Since March 14, people have had to remain in their own provinces.

People will still have to wear masks in public when social distancing measures cannot be observed.
At Madrid’s international Adolfo Suarez-Barajas airport there was a sense of relief for passengers, many of whom were travelling to see loved ones after months apart.
“My situation is a little complicated because my wife lives in Italy and I live in Spain so we haven’t seen each other for four months,” said Alberto Bos, who was flying to Milan.
All arriving passengers will have their temperature taken, submit information about where they have come from, and provide their whereabouts in Spain in case they need to be traced.
Spain’s border with neighbouring Portugal will reopen on July 1 at Lisbon’s request.
Stickers on the floor of the arrivals hall made sure those waiting for passengers complied with social distancing measures.

BACK TO NORMAL

People with suitcases borded trains at Madrid’s Atocha station heading for coastal Valencia, after months confined to Madrid, over 300 kms (186.4 miles) from the seaside.
Meanwhile, French people crossed the border to queue for relatively cheaper tobacco and alcohol in the northern city of Irun.

“Today it’s all getting a bit back to normal. It’s good for the shops, for the economy, for everything,” said shop owner Luis Mancho.
Some 1,500 German tourists touched down in Mallorca early last week as part of a pilot scheme to establish a travel corridor between the two areas, ahead of the lifting of restrictions on Sunday.
“We will allow British visitors to enter Spain just like the rest of the European Union or Schengen area from 21 June freely and without the need for the quarantine,” foreign minister Arancha Gonzalez Laya told BBC News on Saturday.
But Britain’s own quarantine measures, requiring a two-week period of self-isolation for most people entering the country, could put off potential travellers. Britain is due to review its quarantine rule on June 29, three weeks after it was introduced.
Tourism Minister Reyes Maroto said Spain was ready to welcome tourists in an interview with newspaper ABC on Sunday, but added the country has to work to get that message out.
“We have to build trust,” she said. “Translate to travellers, Spaniards and foreigners, that the country is a safe destination.”
Spain, which has recorded more than 245,000 coronavirus cases and over 28,000 deaths, has been easing its lockdown restrictions in recent weeks.
https://www.reuters.com/article/us-health-coronavirus-spain-borders/spain-reopens-its-borders-as-state-of-emergency-comes-to-an-end-idUSKBN23S0BP?il=0

Saturday, June 20, 2020

‘Stress Hormone’ Levels May Indicate Severity of COVID-19

High levels of the stress hormone cortisol are associated with an increased risk of death among COVID-19 patients, according to a new study.
The findings could be used to identify COVID-19 patients who are more likely to require intensive care, the researchers suggested.
Cortisol levels can rise when the body is stressed due to illness. High levels are dangerous, leading to increased risk of infection and poor outcomes.
In order to assess how high cortisol levels affect COVID-19 patients, U.K. researchers assessed 535 patients with suspected COVID-19 who were admitted to three London hospitals between March 9 and April 22.
A COVID-19 swab test and routine blood tests, including a baseline measurement of cortisol levels, were performed within 48 hours of admission. Cortisol levels were significantly higher in the 403 patients confirmed to have COVID-19 than in those without the illness, the findings showed.
Cortisol levels when a person is healthy and resting are 100 to 200 nm/L, and nearly zero during sleep. Levels in the COVID-19 patients in the study were as high as 3,241, much higher even than after major surgery, when levels can exceed 1,000.
Just under 27% of the COVID-19 patients died during the study period, compared to just under 7% of those without COVID-19, the researchers said.
Among the COVID-19 patients, those with a baseline cortisol level of 744 or less survived an average of 36 days, compared with 15 days for those with levels over 744, according to the study.
“From an endocrinologist’s perspective, it makes sense that those COVID-19 patients who are the sickest will have higher levels of cortisol, but these levels are worryingly high,” said study leader Waljit Dhillo.
Dhillo heads the diabetes, endocrinology and metabolism division at Imperial College London.
“Three months ago when we started seeing this wave of COVID-19 patients here in London hospitals, we had very little information about how to best triage people,” Dhillo said in a college news release. Now, “we potentially have another simple marker to use alongside oxygen saturation levels to help us identify which patients need to be admitted immediately, and which may not.”
Having an early indicator of which patients may deteriorate more quickly will help medical personnel provide the best level of care as fast as possible, Dhillo added.
The results were published June 18 in The Lancet Diabetes & Endocrinology.

SOURCE: Imperial College London, news release, June 18, 2020
https://consumer.healthday.com/infectious-disease-information-21/coronavirus-1008/stress-hormone-levels-may-indicate-severity-of-covid-19-758754.html