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Tuesday, December 1, 2020

When and which COVID-19 vaccines are likely to be available in Asia

  Pfizer Inc with partner BioNTech SE, Moderna Inc and AstraZeneca Plc have released trial data this month showing their experimental vaccines are effective in preventing the disease. If regulators approve any of the vaccines in coming weeks, the companies have said distribution could begin almost immediately with governments around the world.

But many Asian countries do not expect to receive big amounts initially, and below are estimated distribution timelines, supply deals announced so far and clinical trials under way in the region.

AUSTRALIA

It has agreed to buy 135 million doses: 34 million from AstraZeneca, 40 million from Novavax Inc, 10 million from Pfizer and 51 million from CSL Ltd.

It expects delivery of 3.8 million doses of AstraZeneca’s vaccine in January and February next year.

CHINA

China has not announced supply deals with Western drugmakers, which instead have partnered with private companies.

AstraZeneca’s vaccine may be approved in China by mid-2021 and its Chinese partner Shenzhen Kangtai Biological Products plans to have annual production capacity of at least 100 million doses of the vaccine by end-2020.

For the Pfizer/BioNTech vaccine, a unit of Shanghai Fosun Pharmaceutical Group plans a Phase 2 trial.

Tibet Rhodiola Pharmaceutical Holding is bringing in Russian vaccine candidate Sputnik V and plans early and mid-stage trials of the shot in China.

China has also approved three vaccine candidates developed by Sinovac and state-owned Sinopharm for emergency use programme, and Sinopharm is hopeful of its two candidates receiving conditional approval for general public use within this year.

JAPAN

Japan has deals to purchase 120 million doses from Pfizer/BioNTech in the first half of next year, 120 million from AstraZeneca, of which first 30 million will be shipped by March 2021, and 250 million from Novavax.

It is also in talks with Johnson & Johnson and has a deal with Shionogi & Co.

Experts said vaccine makers would need to conduct at least Phase 1-2 trials in Japan before seeking approval.

SOUTH KOREA

It aims to secure vaccines for 10 million people from COVAX and 20 million people from separate deals with drugmakers by the end of this year.

It has the “Optional Purchase” arrangement with COVAX that allows it to select vaccines from specific vaccine makers.

The timing of the procurement and the amount depend on the production schedule of those vaccines, according to health officials.

Inoculation is likely to start in the second quarter of next year to allow more time to observe potential side effects.

INDIA

The head of the Serum Institute of India, which makes the AstraZeneca vaccine, said on Nov 23 the positive late-state trial result of the candidate will allow it to seek emergency use authorisation by year-end, before gaining approval for a full rollout by February or March next year.

India also expects a government-backed vaccine to be launched as early as February, while it is conducting a late-stage trial of Sputnik V.

TAIWAN

Taiwan aims to secure around 15 million doses initially, both via the COVAX scheme and by directly purchasing from vaccine makers, and may buy additional 15 million doses.

The government has said it hopes to begin vaccinations in the first quarter of next year.

THE PHILIPPINES

It is in talks with AstraZeneca for the supply of at least 20 million doses, which may arrive in the country in the second quarter of next year. It hopes to lock in 60 million doses in total and also is in talks with Pfizer and Sinovac.

Vaccine makers can apply for approval with the country’s regulators even if no clinical trial is done in the Philippines.

INDONESIA

It is one of the countries listed as 92 low and middle income economies, which means it is entitled to have access to vaccines through COVAX for 20% of its population, or approximately 106-107 million doses if each person gets two injections.

Indonesia is testing Sinovac vaccine and preparing to start mass vaccination for medical staff and other frontline workers as early as late January.

VIETNAM

A government official says vaccines from COVAX would cover only 20% of its population and the country is likely to have a chance to secure separate deals soon as overall demand is very high.

BANGLADESH

Bangladesh signed a deal with India’s Serum to buy 30 million doses of the AstraZeneca vaccine.

It also expects to receive 68 million doses from GAVI at a subsidized rate, a senior health ministry official said.

https://www.reuters.com/article/us-health-coronavirus-vaccines-asia-fact/factbox-when-and-which-covid-19-vaccines-are-likely-to-be-available-in-asia-idUSKBN28B3QD

UK not planning vaccine passports for pubs, theatre, sports events

 Senior British minister Michael Gove said that the government was not planning a system of vaccine passports which would prevent those who hadn’t had a COVID-19 jab from going to the pub or attending events.

“I certainly am not planning to introduce any vaccine passports and I don’t know anyone else in government (who is),” Gove told Sky News on Tuesday.

The minister in charge of vaccines, Nadhim Zadhawi, said on Monday that he expected people who refused the COVID-19 vaccine could find that they were refused entry to restaurants, bars, cinemas and sports venues.

When asked about that, Gove said he did not think people would need a vaccine passport to go to the pub, the theatre or to sports events.

“The most important thing to do is to make sure we vaccinate as many people as possible,” he said.

https://www.reuters.com/article/us-health-coronavirus-britain/uk-not-planning-vaccine-passports-for-pubs-theatre-sports-events-idUSKBN28B42W

European agency to decide on Pfizer's vaccine by Dec. 29, Moderna's by Jan. 12

  The European Medicines Agency said on Tuesday that if its experts have received enough data from drugmakers Pfizer and Moderna about their candidate vaccines against the coronavirus, the agency would complete its reviews by Dec. 29 and Jan. 12, respectively, at latest.

The companies said earlier on Tuesday that they had submitted approval requests for their vaccine candidates to the European drugs regulator.

https://www.reuters.com/article/us-health-coronavirus-vaccines-europe/european-agency-to-decide-on-pfizers-vaccine-by-dec-29-modernas-by-jan-12-idUSKBN28B4P6

AstraZeneca sells former blockbuster cholesterol drug for $320 m

 AstraZeneca said on Tuesday it would sell rights to its erstwhile blockbuster cholesterol drug, Crestor, to German pharmaceutical company Gruenenthal GmbH for an upfront payment of $320 million as the British drugmaker focuses on its cancer treatments portfolio.

Crestor, which brought in revenue of over $5 billion for AstraZeneca in 2015, was among its best-selling medicines and used to contribute to around 20% of the company’s total revenue.

Crestor was hit by the arrival of cheap generic rivals in 2016 and newer medicines such as Tagrisso and Imfinzi for cancer and Fasenra for severe asthma were touted by AstraZeneca as medicines that would take over.

AstraZeneca, which is among the front-runners in the race to develop a vaccine for the novel coronavirus, has been trying to focus on its cancer drugs as it streamlines its business.

The London-listed company has been viewed as having a head start in the race for cancer treatments and sales of those medicines, including blockbuster lung cancer treatment Imfinzi, have been key to its turnaround.

Tuesday’s deal will give Gruenenthal rights to sell Crestor and associated medicines in more than 30 countries in Europe, except the UK and Spain, AstraZeneca said.

AstraZeneca will continue to manufacture and supply the drug to GrĂ¼nenthal during a transition period and will continue to sell it in other regions, including North America and China, it said.

The deal is expected to close in the first quarter of 2021, AstraZeneca said, adding that GrĂ¼nenthal could make milestone payments of up to $30 million.

In October, AstraZeneca said it would sell rights for its heart failure and blood pressure medicines Atacand and Atacand Plus to Germany’s Cheplapharm Arzneimittel GmbH for $400 million.

The British drugmaker said that the divestment of Crestor will not affect its financial guidance for 2020.

https://www.reuters.com/article/us-astrazeneca-divestiture/astrazeneca-sells-former-blockbuster-cholesterol-drug-for-320-million-idUSKBN28B3Z5

Monday, November 30, 2020

Moderna's COVID vaccine scheduled for FDA review on Dec. 17

 

  • Moderna (NASDAQ:MRNA) +6.9% post-market after soaring to another all-time high in today's trade, as the company asked U.S. and European health regulators to authorize use of its COVID-19 vaccine, which was shown to be 94.1% effective - with 100% efficacy in preventing severe COVID - in a full analysis of a pivotal study.
  • A panel of outside experts advising the U.S. Food and Drug Administration will meet Dec. 17 to review the evidence for Moderna's vaccine and vote on whether to recommend that the agency authorize its emergency use; a similar meeting has been set for Dec. 10 for the Pfizer-BioNTech vaccine.
  • It is unclear how long the FDA will take to make a decision on allowing use, but Moderna CEO StĂ©phane Bancel says it is possible the agency could decide within a few days of the advisory panel meeting, or between Dec. 18-20.
  • Both vaccines have shown more than 90% efficacy, and mRNA-1273's less-rigorous distribution and shipping requirements give the Moderna drug a slight edge, though both will be used given current production constraints.
  • Moderna's market value has now reached a record $60B, topping pharma heavyweights such as Vertex and Regeneron, even though it has yet to bring a drug to market.
  • https://seekingalpha.com/news/3640180-modernas-covid-vaccine-scheduled-for-fda-review-on-dec-17

Release of immature blood cells from bone marrow signature of severe COVID-19

 In severe cases of COVID-19 disease, not only classic immune cells play a role. In particular, the release of immature precursor cells from the bone marrow into the blood indicates a particularly severe course of the disease and could contribute to complications. This has been shown by an international research team involving the DFG Cluster of Excellence "Precision Medicine in Chronic Inflammation" (PMI). The team included physicians and researchers from Kiel University (CAU), the University Medical Center Schleswig-Holstein (UKSH) and the Universities of Bonn, Cologne, Luebeck, Tuebingen and Nijmegen as well as the Research Center Borstel—Leibniz Lung Center and the German Centre for Neurodegenerative Disorders (DZNE), together with colleagues from the national DFG research association DeCOI. The findings have been published in the journal Immunity on Thursday, November 26th.

In search of a biomarker for a severe COVID-19 course

Infections with the novel  SARS-CoV2 may result in highly heterogeneous clinical pictures. While many of the infections are mild or even asymptomatic, the disease can become life-threatening, especially in older people. In these severe cases, other organs such as the heart or kidneys can be affected in addition to the lung. A immunological misfiring plays an important role, but findings are accumulating that damage to  and over-activated  are decisive factors for a severe course. One of the most common direct causes of death from COVID-19 is  clots in the lungs.

"Despite numerous studies, we actually know relatively little about the course of the disease over time. Which  play an important role here and when? And can we identify early molecular signatures in the blood that point to severe course of the disease later on? These were questions we asked ourselves at the beginning and we got surprising answers," explains one of the lead authors of the study, Professor Philip Rosenstiel, Director of the Institute for Clinical Molecular Biology (IKMB) at the CAU and the UKSH and member of the steering committee of the Cluster of Excellence PMI.

Two immature blood cell types characteristic of severe course

The team examined blood samples from COVID-19 patients who were hospitalized at the university hospitals in Kiel, Bonn, Cologne and Nijmegen. In a group of 14 patients, circulating  were analyzed in a time series. Blood samples from healthy people were used as a comparison. " The special feature is that we were able to analyze hundreds of thousands of  in parallel with the help of so-called single cell genomics and were thus able to identify rare cell types," explains Dr. Joana Pimenta Bernardes, young scientist of the Cluster of Excellence PMI and postdoc at the IKMB, who is one of the first authors of the study together with the other two young researchers Dr. Florian Tran, Clinician Scientist of the Cluster of Excellence PMI, and Dr. Neha Mishra. Mishra, who is also researching at the IKMB as a postdoc, explains further: "Together with other data such as clinical laboratory values and measurements of inflammatory messengers, we were able to create a kind of fingerprint, a signature, of the altered functioning of these cells and track it over time."

Signatures of two immature cell types are therefore particularly characteristic of severe COVID-19 disease: platelet precursor cells, so-called megakaryocytes, and immature red blood cells. "This is particularly surprising because these precursor cells are normally not in the blood but in the bone marrow, where they mature as needed," explains Tran. "We know of such progenitor cells being washed out into the blood of seriously ill patients, for example in bacterial sepsis (blood poisoning). This has not yet been described for COVID-19," Tran continues.

"With the help of high-precision cellular genomic analyses, we were able to draw a very detailed picture of the cellular changes throughout the course of the disease. While previously we mainly looked at immune cells, we were now able to find cell types that had previously been overlooked," says Joachim Schultze, professor at the University of Bonn and research group leader at the DZNE, one of the last authors of the study.

Possible explanation for coagulation problems with COVID-19 found

The scientists gained important insights from a group of 39 COVID-19 patients who had been treated in the intensive care unit in Nijmegen, i.e. had particularly severe courses of disease. In this group of patients, a signature of the megakaryocytes and red blood cell progenitor cells was particularly strong in patients who died of the disease compared to patients who recovered. "The megakaryocytes reflect a well-known COVID-19 problem: blood platelets are responsible for blood coagulation. One of the most common direct causes of death from COVID-19 is coagulation problems. The emergency-activated megakaryocytes in the blood may produce platelets that aggregate more easily and thus lead to the coagulation problems," assumes Rosenstiel . The increase in red blood cell progenitor cells indicates a lack of oxygen and is known as an emergency reaction in severe lung diseases.

Together to success

The study has been made possible by the nationwide consortium—the "German COVID-19 OMICS Initiative" (DeCOI) - and was carried out in cooperation with partners from the "Human Cell Atlas," an international consortium for single cell analysis. "It was only through this teamwork that the complex analyses and interpretation of the data could be mastered in the short time available," says Schultze, who is also the coordinator of the DeCOI consortium.

"With the present work, we have now created the basis for validating novel biomarkers at an early stage of COVID-19 disease to identify patients at risk for a severe course of the . This would enable us to improve the care of particularly severely affected patients even more specifically," says Professor Stefan Schreiber, Director of the Clinic for Internal Medicine I, UKSH, Campus Kiel, Director at the IKMB and spokesperson of the Cluster of Excellence PMI. "I am particularly pleased that three young researchers from the PMI Cluster of Excellence have been significantly involved in this work as lead authors, including one of our Clinician Scientists. This shows how the young researchers in the cluster are already doing excellent research with relevance for society."

More information: Joana P. Bernardes et al. Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories, Immunity (2020). DOI: 10.1016/j.immuni.2020.11.017

https://medicalxpress.com/news/2020-11-immature-blood-cells-bone-marrow.html

Pandemic to delay cancer advances nearly 18 months, researchers fear

 Cancer researchers fear advances for patients could be delayed by almost a year and a half because of the effects of the COVID-19 pandemic, a new survey reveals.

Scientists at The Institute of Cancer Research, London, told the survey that their own research advances would be pushed back by an average of six months by the initial lockdown, subsequent restrictions on laboratory capacity and the closure of national scientific facilities.

With broader effects on charity funding, disruption of collaboration and personal interaction between scientists, and diversion of research efforts to COVID-19, the respondents estimated that major advances in  would be delayed by an average of 17 months.

But the researchers said science had now adapted in many ways to the pandemic and that long-lasting damage to cancer research could be mitigated through extra funding from charitable donations or Government support—calling for investment in staffing, new technology such as robotics and computing power.

Making up for lost time

The Institute of Cancer Research (ICR), which has discovered more cancer drugs than any other academic center in the world, has like many research organizations been hit by cuts to its own fundraising income and to grants from other charities. The ICR had to pause much of its work during the initial lockdown, and is now running a major fundraising appeal to help kick-start its research and make up for lost time.

The ICR surveyed 239 of its researchers in order to detail the impact the pandemic has had on its research and to point towards ways of moving research forward again as quickly as possible.

Respondents said they had lost an average of 10 weeks of research time to the first lockdown itself, and that their own scientific advances would be pushed back by an average of six months. Almost all said COVID-19 had had an impact on their work—with 36 percent saying it had had a 'moderate' impact, another 36 percent a 'substantial' impact and 5 percent an 'extreme' impact.

Some 91 percent said the biggest problem had been the closure of labs during lockdown and subsequent restrictions in access to facilities and equipment—citing, for example, closure of major, national research facilities. The average ICR researcher spent 53 percent of their working time in a lab before lockdown, plummeting to 5 percent during lockdown and since recovering to 34 percent.

The next most cited impacts were inability to enroll patients on  (60 percent), to access clinical samples (46 percent) or to interact in person with colleagues (41 percent) – with video conferencing seen as a poor substitute for meeting in person at conferences and other events.

Keeping labs open to prevent further disruption

Many researchers were, however, able to use the time productively—for example through doing training (48 percent), or carrying out desk-based (62 percent) or computational (33 percent) research. Some carried out research into COVID-19 (5 percent), including studies that have given us greater insight into the effects of COVID-19 on cancer treatment pathways.

But the survey nevertheless laid bare the emotional impact of the pandemic on researchers. Some 69 percent of researchers said the impact of the pandemic on their work had left them 'frustrated," 39 percent had been 'saddened' and 25 percent 'depressed."

The respondents were strongly supportive of efforts to keep labs open to prevent any further disruption to research advances for cancer patients. The ICR's labs have managed to stay open during the second lockdown period while taking significant measures to help prevent risk of spread.

The ICR's researchers did feel that science had adapted to COVID-19 and that there were various ways to make up for lost time—over 60 percent felt funding for extra staff time would help; almost 40 percent wanted upgrades in technology, for example for robotics, and 29 percent increased computing power.

Inspiring to see how researchers have adapted

Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said:

"Our researchers are passionate about making advances to benefit patients, so it has been hugely frustrating that their work has been so disrupted, although also inspiring to see how well they have adapted to the restrictions the pandemic has imposed on our lives.

"It is sobering to see that our researchers are estimating that their own research advances will be delayed by six months—and that the wider impact, because of the interconnectedness of science, is likely to push back major advances for patients by nearly a year and a half.

"Our survey though does provide solutions to mitigate the impact—in the form of investment in staffing, new technologies and computing power. For that, we need more of the generous donations we have been receiving to our emergency appeal, along with a commitment from the Government to help fill the funding gap for the life sciences left by the pandemic."

Impossible to replace the light bulb moments from being together

Dr. Sebastian Guettler, deputy head of structural biology at The Institute of Cancer Research, London, said:

"Our work is reliant on access to shared infrastucture in London and nationally, and during the first lockdown this became impossible. These facilities have now introduced or widened remote access—we can control experiments hundreds of miles away from our own homes, with good broadband internet speeds. But we continue to be limited when it comes to preparing samples in the lab, which are then shipped to these facilities for experiments. It's been an intensely frustrating time, and some teams are much more affected than others—depending on which facilities they need.

"The coronavirus has also reduced or stopped the spontaneous interactions with colleagues that science is so dependent on for generating new ideas. Video conferencing has helped us stay connected as a lab and a community, but it's not a true replacement for those light bulb moments you might get from chatting with someone at a conference or over coffee in the canteen.

"There are some positives from this period. Being able to access shared facilities remotely will be helpful in the future, and we know we can make up for some of the lost time if we have more funding for people and equipment to catch up on the lost laboratory work."

Improving clinical research after COVID

Professor Emma Hall, deputy director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, said:

"Our work relies on new clinical trials starting up and existing ones continuing to happen—and COVID-19 has made that incredibly challenging. The pandemic has meant that it will take longer to answer the questions asked in our trials, and that will delay new treatments getting to patients.

"During the initial lockdown, non-COVID clinical research pretty much shut down within the NHS. A lot of our trials were effectively paused because the hospitals that host them had to redeploy resources to COVID-19 research or treatment.

"COVID-19 has forced some changes in how we work that are for the better though. We can capture and manage data remotely rather than relying on paper. The COVID-19 trials have also shown how research can benefit from easier access to routine medical data—hopefully this will be translated to other clinical research and mean more streamlined, simpler to run trials.

"I hope we can use this experience to benefit cancer patients in the long term, but that will only be possible with more support or future advances will be delayed."

The impact of the pandemic on patients

Mother of two Sally Steadman-South, from Sheffield, is living with stage 4 melanoma. She was first diagnosed in 2014 at the age 35, after having a mole removed on her chest. Despite trying numerous treatments including surgery, radiotherapy and immunotherapy, the cancer continued to spread.

For the last two years she has been on the targeted drugs, dabrafenib—a treatment underpinned by the ICR's science—and trametinib, and currently has no evidence of disease.

This year Sally celebrated her 40th birthday with her family—a milestone she never thought she would reach.

Sally shared her concerns about the impact of COVID-19 on cancer patients:

"The coronavirus has been especially devastating for many cancer patients—I have been lucky my treatment has been unaffected but we know many have not and their care has been affected. It's also clear that future research advances have also been delayed.

"I feel lucky that my treatment has worked well so far but I know that the  could become resistant to the drugs at any time. When you get a diagnosis like mine it changes what time means to you—maybe this pandemic has made many more people value and appreciate quality time with family and loved ones. I want to be around for school plays and sports days, see my daughter go to secondary school and see my son enjoy his time there too and start planning his own future.

"We recently went to pick our Christmas tree and they are planting fields of new trees which will be ready in 2028. We agreed that this would be our new goal. I would be there to see this new field of Christmas trees and we would go as a family to pick one. We need to make up for the time lost to this virus so people like me can live longer and make important memories like these."


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Nearly one in five cancer patients less likely to enroll in clinical trials during pandemic