Saturday, February 8, 2025
Home Blog Page 132

Healx partners with Children’s Tumor Foundation to progress neurofibromatosis treatments; recruits patient advocate to lead collaborative drug discovery efforts

0

April 15, 2020: “Healx, the AI-powered and patient-inspired tech company specialising in accelerating the discovery and development of rare disease treatments, today announced a partnership with US and Europe-based patient group Children’s Tumor Foundation (CTF) to progress new AI-derived therapies for neurofibromatosis (NF).

NF is a rare genetic disorder that affects 1 in 3,000 people worldwide. Currently, no treatments exist for any of the three types of NF (NF1, NF2 and schwannomatosis). Healx will combine its AI technology and drug discovery expertise with the disease data, networks and patient insights of CTF to predict and progress novel therapies for NF1.

Leading the collaborative drug discovery efforts is Simone Manso who joins Healx as Head of NF Strategic Partnerships. Simone also serves as a member of CTF’s Board of Directors (BoD) and is the Chairman of CTF Europe’s BoD.

Simone Manso, Head of Neurofibromatosis Strategic Partnerships at Healx said: “Healx has the tech and pharmacology expertise, along with the ability to quickly move treatments towards patients, whilst CTF brings the strong NF know-how and patient, clinical and academic networks. Most importantly, both teams have a shared passion for striving to improve the quality of life for NF patients. I can’t think of a better partnership and I am honoured to lead this effort, which is personally, very close to my heart. This is where the magic can happen!”

Dr Annette Bakker, President of CTF commented: “We at CTF are very excited about this partnership. It is very encouraging that Healx is committed to developing innovative treatments for NF patients in collaboration with CTF. CTF will facilitate the translation of Healx’s comprehensive AI-based discoveries into clinical benefit using our non-profit R&D enabling platform.

The partnership marks the latest in a growing number of collaborative projects between Healx and patient groups worldwide – spanning multiple disease areas (including rare cancers, metabolic and neurological disorders). Healx’s most advanced project currently is with the US-based patient group FRAXA Research Foundation, which has progressed a number of new therapies for fragile X syndrome from the drug prediction stage, to being ready for clinical testing – in just 24 months.

Whilst Healx has recently taken on extra work to use AI and repurposing to help find treatments to target COVID-19, the Company continues to move forward with their primary mission to develop new therapies for rare disease patients. This collaboration with CTF will accelerate their work in NF.

In addition to the CTF collaboration, Healx recently closed the first call for applications to its Rare Treatment Accelerator – a global partnering programme that gives patient groups and Healx the opportunity to work together to progress new rare disease treatments. Healx has committed $20 million in AI drug discovery resources over the next two years to this programme and will be announcing more details on the chosen collaborations in the next few months.”
https://www.cambridgenetwork.co.uk/news/healx-partners-children%E2%80%99s-tumor-foundation-progress-neurofibromatosis-treatments-recruits

First UN solidarity flight departs Addis Ababa carrying vital COVID-19 medical supplies to all African nations

0

April 14, 2020: “The first United Nations “Solidarity Flight” is scheduled to leave Addis Ababa, Ethiopia, from there the aircraft will transport the vital medical cargo to all countries in Africa, where supplies are desperately needed to contain the spread of COVID-19.

WHO cargo is being  transported by the United Nations World Food Programme (WFP), and includes face shields, gloves, goggles, gowns, masks, medical aprons and thermometers, as well as ventilators.

The cargo also includes a large quantity of medical supplies donated by the Prime Minister Abiy Ahmed and Jack Ma Foundation Initiative to reverse COVID-19 in Africa. The African Union, through the Africa Centres for Disease Control and Prevention (Africa CDC) is providing technical support and coordination for the distribution of the supplies.

“Commercial flights are grounded and medical cargo is stuck. We can stop this virus in its tracks, but we’ve got to work together. WFP is committed to getting vital medical supplies to front lines and shielding medical workers as they save lives,” said David Beasley, WFP’s Executive Director. “Our air bridges need to be fully funded to do this, and we stand ready to transport frontline health and humanitarian workers as well as medical cargo,” he added.

“The Solidarity Flight is part of a larger effort to ship lifesaving medical supplies to 95 countries,” said Dr. Tedros Adhanom Ghebreyesus, Director-General of WHO. “I would like thank the African Union, the governments of UAE and Ethiopia, the Jack Ma Foundation and all our partners for their solidarity with African countries at this critical moment in history.” 

The crucial WHO cargo includes one million face masks, as well as personal protective equipment, which will be enough to protect health workers while treating more than 30 000 patients across the continent and laboratory supplies to support surveillance and detection.

“The African Union values the efforts of our partners – the World Health Organization, the World Food Programme, the Jack Ma Foundation/Prime Minister Abiy Ahmed – in supporting the African continental strategy for COVID-19 response. The medical supplies are much needed at this critical time that medical commodities are in short supply worldwide,” said Moussa Faki Mahamat, Chairperson of the African Union Commission. “The African Union will continue to provide the coordination needed as well as resources to ensure that our Member States are able to meet the need for healthcare services during this pandemic,” he added.  

“We have seen time and again our health workers fall victim to infectious diseases as they work in hospitals and sometimes pass away,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “This is unacceptable. This personal protective equipment will help keep them safe. WHO is committed to protecting those on the front-lines of health care.”

WHO’s logistics hub in Dubai, staffed by a team of seven, has been working around the clock to dispatch over 130 shipments of PPE and laboratory supplies to 95 countries across all six WHO regions.

“Thanks to the Government of the United Arab Emirates for its generous support of this operation, WHO’s regional logistics hub in Dubai has played a key role in making sure these supplies are prepared and shipped to where they are most needed. This is by far the largest single shipment of supplies since the start of the pandemic, and will ensure that people living in countries with some of the weakest heaths systems are able to get test and treated, while ensuring that health workers on the frontlines are properly protected,” said Dr Ahmed Al-Mandhari, WHO Regional Director for the Eastern Mediterranean.

The WFP and WHO extend thanks to the Government of Ethiopia, which helped WFP set up the Addis Ababa Humanitarian Air Hub this week, to help transport protective equipment, medical supplies and humanitarian workers across Africa for the COVID-19 response, as well as ensuring medical evacuations for humanitarian responders.

A team of 25 WFP aviation and logistics staff is based at Bole International Airport in Addis Ababa, managing the 24-hour operation. They manage warehouse space for dry bulk, temperature-controlled and cold storage cargo and its onward transport by air. WFP also provides dedicated cargo tracking, warehouse management and customer service to countries across Africa in collaboration with the Africa CDC. 

“The medical supplies are timely as the continent still has a window of opportunity to fight the COVID-19 pandemic. Collective and fast actions as exemplified by the Solidarity Flight are therefore critical,” said John Nkengasong, Director of the Africa CDC. 

As part of a global appeal to raise a US$2 billion for the COVID-19 response, launched by the United Nations Office for Coordination of Humanitarian Affairs (OCHA) on 25 March, WFP is calling for US$350 million to establish vital humanitarian hubs around the world to facilitate the storage and dispatch of essential medical cargo, set up air transport links for cargo and personnel, contract charter vessels for shipping services, and provide passenger air and Medevac services for humanitarian and health workers. This includes such Solidary Flights through Addis Ababa.  Currently, WFP has received only 24% (US$84 million) of the US$350 million it requires to provide these vital common services to the global humanitarian community.”
https://www.who.int/news-room/detail/14-04-2020-first-un-solidarity-flight-departs-addis-ababa-carrying-vital-covid-19-medical-supplies-to-all-african-nations

WHO Director-General’s Statement on IHR Emergency Committee on Ebola Virus Disease in the Democratic Republic of the Congo

0

14 April 2020: “The International Health Regulations Emergency Committee for Ebola in the Democratic Republic of the Congo (DRC) met and has advised me that in its view the Ebola outbreak in the DRC continues to constitute a Public Health Emergency of International Concern. I have accepted that advice.

Tremendous progress has been made containing this outbreak in very difficult circumstances. Up until Friday, 54 days had passed without a confirmed case being reported, and 40 days had passed since the last person known to have Ebola tested negative and was discharged from treatment.

Since Friday, three new cases have been confirmed – two in people who died in the community, and one person who was in contact with one of them. The source of their infection is still under investigation. It is likely that additional cases will be identified.

Flare-ups are expected at the tail-end of Ebola outbreaks. Our teams in Beni are experienced in responding to new cases, and acted quickly to engage with affected communities, investigate alerts, identify and vaccinate contacts, decontaminate affected homes and health facilities, and send samples for sequencing.

The Committee noted that armed groups are active in the area where these cases were identified, a lack of funding is constraining the response, and the COVID-19 pandemic is adding more challenges to an already complex operation.

We have to anticipate and be prepared for additional small outbreaks. We need the full force of all partners to bring these outbreaks under control and to meet the needs of the people affected. 
I thanks to the members of the Committee for their advice. And I thank the government and people of DRC, the responders, partners and WHO colleagues, who are dedicated to ending this outbreak.”
https://www.who.int/news-room/detail/14-04-2020-who-director-general-s-statement-on-ihr-emergency-committee-on-ebola-virus-disease-in-the-democratic-republic-of-the-congo

Sanofi and GSK to join forces in unprecedented vaccine collaboration to fight COVID-19

0

April 14, 2020: “Sanofi and GSK announce that they have signed a letter of intent to develop an adjuvanted vaccine for COVID-19, using innovative technology from both companies, to help address the ongoing pandemic. 
 
Sanofi will contribute its S-protein COVID-19 antigen, which is based on recombinant DNA technology. This technology has produced an exact genetic match to proteins found on the surface of the virus, and the DNA sequence encoding this antigen has been combined into the DNA of the baculovirus expression platform, the basis of Sanofi’s licensed recombinant influenza product in the US. 
 
GSK will contribute its proven pandemic adjuvant technology. The use of an adjuvant can be of particular importance in a pandemic situation since it may reduce the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and therefore contributing to protect more people.  
 
“As the world faces this unprecedented global health crisis, it is clear that no one company can go it alone.” says Paul Hudson, Chief Executive Officer, Sanofi. “That is why Sanofi is continuing to complement its expertise and resources with our peers, such as GSK, with the goal to create and supply sufficient quantities of vaccines that will help stop this virus.”

“This collaboration brings together two of the world’s largest vaccines companies.” says Emma Walmsley, Chief Executive Officer, GSK. “By combining our scientific expertise, technologies and capabilities, we believe that we can help accelerate the global effort to develop a vaccine to protect as many people as possible from Covid-19.”

The combination of a protein-based antigen together with an adjuvant is well-established and used in a number of vaccines available today. An adjuvant is added to some vaccines to enhance the immune response and has been shown to create a stronger and longer- lasting immunity against infections than the vaccine alone. It can also improve the likelihood of delivering an effective vaccine that can be manufactured at scale.  
 
The companies plan to initiate phase I clinical trials in the second half of 2020 and, if successful, subject to regulatory considerations, aim to complete the development required for availability by the second half of 2021.  

As previously announced by Sanofi, development of the recombinant-based COVID-19 vaccine candidate is being supported through funding and a collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services. The companies plan to discuss funding support with other governments and global institutions prioritising global access.

“Strategic alliances among vaccine industry leaders are essential to make a coronavirus vaccine available as soon as possible,” says BARDA Director, Rick A. Bright, Ph.D. “Development of the adjuvanted recombinant-based COVID-19 vaccine candidate holds the potential to lower the vaccine dose to provide vaccine to a greater number of people to end this pandemic, and help the world become better prepared or even prevent future coronavirus outbreaks.”

The companies have set up a Joint Task Force, co-chaired by David Loew, Global Head of Vaccines, Sanofi and Roger Connor, President Vaccines, GSK. The taskforce will seek to mobilize resources from both companies to look for every opportunity to accelerate the development of the candidate vaccine. 

Considering the extraordinary humanitarian and financial challenge of the pandemic, both companies believe that global access to COVID-19 vaccines is a priority and are committed to making any vaccine that is developed through the collaboration affordable to the public and through mechanisms that offer fair access for people in all countries. 
  
These efforts mark a significant milestone in Sanofi’s and GSK’s ongoing contributions to help fight COVID-19. The companies have entered into a Material Transfer Agreement to enable them to start working together immediately.  Definitive terms of the collaboration are expected to be finalised over the next few weeks.”
https://www.sanofi.com/en/media-room/press-releases/2020/2020-04-14-13-00-00

AstraZeneca initiates CALAVI clinical trial with Calquence against COVID-19

0

April 14, 2020: “AstraZeneca will initiate a randomised, global clinical trial to assess the potential of Calquence (acalabrutinib) in the treatment of the exaggerated immune response (cytokine storm) associated with COVID-19 infection in severely ill patients. The trial design is based upon strong scientific evidence supporting the role of the Bruton’s tyrosine kinase (BTK) pathway in the production of inflammatory cytokines and on encouraging early clinical data. Calquence is a next-generation, highly selective BTK inhibitor currently used to treat certain types of blood cancers.

The trial, called CALAVI, is based on early clinical data with Calquence demonstrating that a decrease in inflammation caused by BTK inhibition appears to reduce the severity of COVID-19-induced respiratory distress. The goal of the trial is to evaluate the efficacy and safety of adding Calquence to best supportive care (BSC) to reduce mortality and the need for assisted ventilation in patients with life-threatening COVID-19 symptoms.

This large, multicentre, global, randomised trial uses a two-part patient-centric design developed in record time to accelerate data capture and analysis. Part one evaluates the addition of Calquence to BSC versus BSC alone in patients hospitalised with COVID-19 who are not in the intensive care unit (ICU). Part two evaluates the addition of Calquence to BSC in a cohort of patients in the ICU.

José Baselga, Executive Vice President, Oncology R&D, said: “With this trial we are responding to the novel insights of the scientific community and hope to demonstrate that adding Calquence to best supportive care reduces the need to place patients on ventilators and improves their chances of survival. This is the fastest launch of any clinical trial in the history of AstraZeneca.”

Louis M. Staudt, M.D., Ph.D., Chief of the Lymphoid Malignancies Branch at the National Cancer Institute (NCI), said: “Given the well documented role of the protein BTK in regulating inflammation, it is possible that inhibiting BTK with acalabrutinib could provide clinical benefit in patients with advanced COVID-19 lung disease. As with all new treatments, it will be necessary to gather data from clinical trials in order to understand the best and safest treatment options for patients.”

The CALAVI trial is expected to open for enrolment in the coming days in the US and several countries in Europe. Wyndham H. Wilson, MD, PhD, of NCI in the US, will serve as the principal investigator of the trial. Louis M. Staudt, MD, PhD will serve as senior investigator.

CALAVI: CALAVI is a large, randomised, open-label, multicentre, global, two-part trial evaluating the efficacy and safety of Calquence with BSC versus BSC alone in patients hospitalised with respiratory complications of COVID-19. Part one is randomised (2:1) and evaluates the addition of Calquence to current BSC in patients who are hospitalised but not on assisted ventilation and not in the ICU. Part two evaluates the addition of Calquence to BSC in a cohort of patients in the ICU with more severe respiratory complications. The trial is being conducted in multiple sites around the world. The primary endpoint measures the use of assisted ventilation or death.

COVID-19: Coronavirus disease 2019 (COVID-19) is a new pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most COVID-19 cases (~80%) are mild respiratory illnesses. However, some require hospitalisation, mostly due to pneumonia, and can progress quickly to severe acute lung injury and acute respiratory distress syndrome (ARDS), which is associated with high mortality.A viral-induced cytokine storm or “hyperimmune response” is hypothesised to be a major pathogenic mechanism of ARDS in these patients through modulation of pulmonary macrophages and dendritic cells and/or neutrophils.

Calquence: Calquence is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity. In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

Calquence (acalabrutinib) is approved for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) in the US and a few other countries with an active global filing programme. In addition, Calquence is indicated for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in the US and several other countries.

BTK Inhibition: In lung macrophages, BTK is a key regulator of the production of multiple cytokines and chemokines including TNFa, IL-6, IL-10, and MCP-1, among others.  BTK inhibition reduces the production of these cytokines and is, therefore, a promising strategy to reduce the respiratory complications of COVID-19.

There is evidence that dysregulated BTK-dependent macrophage signalling may be central to the exaggerated inflammatory responses to SARS-COV-2 and play a role in COVID-19 pneumonia and ARDS.In macrophages, TLR3, TLR7 and TLR8 can recognise single strand RNA from viruses such as SARS-COV-2 and initiate signalling through BTK-dependent activation of NF-kB and IRF3, triggering the production of multiple inflammatory cytokines and chemokines.In support of the role of BTK inhibition, therapeutic inhibition of BTK in patients with lymphoid malignancies results in decreased proinflammatory cytokines and chemokines. Similar findings have been observed in mouse influenza models, where BTK inhibition also decreased these inflammatory mediators and rescued mice from lethal acute lung injury.” https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazeneca-initiates-calavi-clinical-trial-with-calquence-against-covid-19.html

A new Rutgers coronavirus test based on a simple spit into a tube will come to a N.J. testing site this week

0

 April 13, 2020: “A new COVID-19 test developed at Rutgers University that uses saliva samples instead of nasal and throat swabs has gotten emergency approval by the Food and Drug Administration, and is expected to be put out into the field as early as Wednesday.

The test will mean people will need only spit into a tube, rather than submit to swabbing deep into their nasal passages to obtain samples — the current conventional testing method that can be uncomfortable, often painful, and has limited testing nationwide.

Officials said the saliva tests, coupled with a genetic testing service for the coronavirus also developed at Rutgers that can process thousands of samples daily, offering a route to large-scale testing that will be able to greatly increase the numbers of people screened for COVID-19.

“It truly expands the ability to collect and test more samples, not just for us, but for everyone,” said Andrew Brooks, chief operating officer and director of technology development at Rutgers’ RUCDR Infinite Biologics.

RUCDR developed the collection method and a new lab method to greatly increase the number of tests that can be done, in partnership with Spectrum Solutions and Accurate Diagnostic Labs.

The saliva tests will initially be made available to the RWJBarnabas Health network, which has partnered with Rutgers University and includes Robert Wood Johnson University Hospital in New Brunswick and University Hospital in Newark. Those tests will be initially deployed at a Middlesex County coronavirus drive-thru facility on Kilmer Road in Edison, for county residents and first responders, beginning Wednesday. Results are expected to be reported back within 24 to 48 hours, according to county officials.

The FDA granted emergency use authorization to RUCDR and its partners for the saliva collection approach on Friday, which officials said was the first such approval granted by the federal agency. The saliva samples will be analyzed at a Rutgers lab, which also received FDA approval, and will be able to analyze as many as 10,000 samples daily, by using automated lab equipment to perform “nuclear extractions” from collected specimens.

Whether by swab or saliva, the science for detecting COVID-19 is typically the same, utilizing what is known as “standard QPCR approaches.” It’s the same type of molecular analysis already being used in New Jersey. But while highly accurate, the turnaround time for the current testing is slow and the collection of samples through nose swabs is arduous and labor-intensive. The saliva tests, together with new Rutgers-based lab, will make it possible to far expand testing capabilities, said Brooks, who also is a professor in the university’s Department of Genetics.

“We can significantly increase the number of people tested each and every day, as self-collection of saliva is more quick and scalable than swab collections,” Brooks said.

In its authorization letter to Rutgers, the FDA said the test should only be performed “in a health care setting under the supervision of a trained health care provider.” The FDA has not cleared any COVID-19 tests for use at home, though several companies have announced plans to make them available. Additionally, the FDA said patients who test negative with the saliva-based kit should have their results confirmed with a second testing method.” https://www.nj.com/coronavirus/2020/04/a-new-rutgers-coronavirus-test-based-on-a-simple-spit-into-a-tube-will-come-to-a-nj-testing-site-this-week.html

BD Announces Second FDA Emergency Use Authorization, CE Mark for New COVID-19 Molecular Diagnostic for Global Use

0

April 13, 2020: “BD (Becton, Dickinson and Company), a leading global medical technology company announced that the U.S. FDA  has granted Emergency Use Authorization (EUA) for an additional molecular diagnostic test for COVID-19 that can return results in two to three hours. The new test also has been CE marked to the IVD Directive (98/79/EC).

The test, which is run on the BD MAX™ System, provides additional testing capacity for COVID-19 in the United States and in countries that recognize the CE Mark to test patients and health care workers. The test is in addition to the other tests already available on the BD MAX™ System from collaborations with BioGX and CerTest and is based on the CDC assay design. The BD MAX™ System, a molecular diagnostic platform, is already in use at thousands of laboratories worldwide, and each unit is capable of analyzing hundreds of samples over a 24-hour period.

“The new BD COVID-19 test for the BD MAX™ System will help increase availability of these much-needed tests around the world,” said Dave Hickey, president of Integrated Diagnostics for BD. “We continue to work towards a full portfolio of testing options to give health care workers choice and access to the right test for the right situation.”

The majority of BD MAX™ Systems are installed in hospital laboratories, reducing the added time and complexity of needing to send samples to a reference lab. The system is fully automated, reducing the opportunity for human error and increasing the speed to result, and can process 24 samples simultaneously. The assay is based on the same viral RNA targeting sequences and real-time PCR detection method as the test developed by the U.S. Centers for Disease Control and Prevention (CDC).

Hospitals and laboratories that use a BD MAX™ System can order tests through their BD sales representative.

The BD SARS-CoV-2 Reagent Kit for BD MAX™ System has been CE marked to the IVD Directive (98/79/EC), but it has not been cleared or approved by FDA. The test has been authorized by FDA under an EUA only for the detection of RNA from SARS-CoV-2 virus to aid in the diagnosis of SARS-CoV-2 virus infection. It has not been authorized for use to detect any other viruses or pathogens. The test is authorized in the United States for the duration of the declaration that circumstances exist justifying the authorization of emergency use of in vitro diagnostic tests for detection and/or diagnosis of COVID-19 under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.”
https://fda.einnews.com/article/514526914?lcf=8DWPqPuUsDVNDakfEIxsCA%3D%3D

AstraZeneca-Merck genetic disorder treatment wins FDA nod

0

April 14, 2020: A treatment developed by AstraZeneca Plc and Merck & Co Inc for a rare genetic disorder was approved by the U.S. Food and Drug Administration Tuesday, the companies said.

Koselugo has been approved for the treatment of paediatric patients aged two years and older with a type of neurofibromatosis, which is a crippling genetic disease affecting one in every 3,000 to 4,000 individuals. https://fda.einnews.com/article/514537392?lcf=8DWPqPuUsDVNDakfEIxsCA%3D%3D

Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization to Decontaminate Millions of N95 Respirators

0

April 12, 2020: “The U.S. Food and Drug Administration issued an emergency use authorization (EUA) that has the potential to decontaminate approximately 4 million N95 or N95-equivalent respirators per day in the U.S. for reuse by health care workers in hospital settings.

“Our nation’s health care workers are among the many heroes of this pandemic and we need to do everything we can to increase the availability of the critical medical devices they need, like N95 respirators,” said FDA Commissioner Stephen M. Hahn, M.D.

“FDA staff continue to work around the clock, across government and with the private sector to find solutions. This authorization will help provide access to millions of respirators so our health care workers on the front lines can be better protected and provide the best care to patients with COVID-19.”

The FDA granted the EUA to Advanced Sterilization Products (ASP) for the STERRAD Sterilization Cycles (STERRAD 100S Cycle, STERRAD NX Standard Cycle, or STERRAD 100NX Express Cycle), which uses vaporized hydrogen peroxide gas plasma sterilization. There are approximately 9,930 STERRAD Sterilization systems in approximately 6,300 hospitals across the U.S. STERRAD 100S Cycle, STERRAD NX Standard Cycle and STERRAD 100NX Express Cycle vary in reprocessing times from 55 minutes, to 28 minutes, and 24 minutes. Each can reprocess approximately 480 respirators per day.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.” https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-decontaminate-millions-n95

FDA Approves AstraZeneca’s First Therapy for Children with Debilitating and Disfiguring Rare Disease

0

April 10, 2020: “U.S. FDA approved AstraZeneca’s Koselugo (selumetinib) for the treatment of pediatric patients, 2 years of age and older, with neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves. Koselugo is the first drug approved by the FDA to treat this debilitating, progressive and often disfiguring rare disease that typically begins early in life.

“Everyone’s daily lives have been disrupted during the COVID-19 pandemic, and in this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life threatening diseases, and their unique needs, a top priority. We continue to expedite product development for these patients,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

Koselugo is approved specifically for patients who have symptomatic, inoperable plexiform neurofibromas (PN), which are tumors involving the nerve sheaths (coating around nerve fibers) and can grow anywhere in the body, including the face, extremities, areas around the spine and deep in the body where they may affect organs. Koselugo is a kinase inhibitor, meaning it functions by blocking a key enzyme, which results in helping to stop the tumor cells from growing.

NF1 is a rare, progressive condition caused by a mutation or flaw in a particular gene. NF1 is usually diagnosed in early childhood and appears in an estimated 1 out of every 3,000 infants. It is characterized by changes in skin coloring (pigmentation), neurologic and skeletal impairments and risk for development of benign and malignant tumors throughout life. Between 30% and 50% of patients born with NF1 develop one or more PNs.

“We are committed to regulatory flexibility and providing extensive guidance to industry in an effort to bring drugs forward that fulfill unmet medical needs. Koselugo represents this commitment,” noted Pazdur. “For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1.”

The FDA approved Koselugo based on a clinical trial conducted by the National Cancer Institute of pediatric patients who had NF1 and inoperable PN (defined as a PN that could not be completely removed without risk for substantial morbidity to the patient). The efficacy results were from 50 of the patients who received the recommended dose and had routine evaluations of changes in tumor size and tumor-related morbidities during the trial. Patients received Koselugo 25 mg/m2 orally twice a day until disease progression or until they experienced unacceptable adverse reactions. The clinical trial measured the overall response rate (ORR), defined as the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3-6 months. The ORR was 66% and all patients had a partial response, meaning that no patients had complete disappearance of the tumor. Of these patients, 82% had a response lasting 12 months or longer.

Other clinical outcomes for patients during Koselugo treatment including changes in PN-related disfigurement, symptoms and functional impairments. Although the sample sizes of patients assessed for each PN-related morbidity (such as disfigurement, pain, strength and mobility problems, airway compression, visual impairment and bladder or bowel dysfunction) were small, there appeared to be a trend of improvement in PN-related symptoms or functional deficits during treatment.

Common side effects for patients taking Koselugo were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain (pain in the body affecting bones, muscles, ligaments, tendons and nerves), fever, acneiform rash (acne), stomatitis (inflammation of the mouth and lips), headache, paronychia (infection in the skin that surrounds a toenail or fingernail) and pruritus (itching).”

“Koselugo can also cause serious side effects including heart failure (manifested as ejection fraction decrease, or when the muscle of the left ventricle of the heart is not pumping as well as normal) and ocular toxicity (acute and chronic damage to the eye) including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision. Patients should have cardiac and ophthalmic assessments performed prior to initiating Koselugo and at regular intervals during treatment. Koselugo can also cause increased creatinine phosphokinase (CPK). CPK is an enzyme found in the heart, brain and skeletal muscles. When muscle tissue is damaged, CPK leaks into a person’s blood. CPK elevation in a patient receiving Koselugo should prompt an evaluation for rhabdomyolysis (breakdown of skeletal muscle due to direct or indirect muscle injury). Koselugo should be withheld, dosage reduced or dosage permanently discontinued based on the severity of adverse reactions. Further, Koselugo contains Vitamin E, and patients are at an increased risk of bleeding if their daily intake of Vitamin E exceeds the recommended or safe limits.

Based on findings from animal studies, Koselugo may cause harm to a newborn baby when administered to a pregnant woman. The FDA advises health care professionals to tell females of reproductive age, and males with female partners of reproductive potential, to use effective contraception during treatment with Koselugo, and for one week after the last dose.

The FDA granted this application Priority Review and Breakthrough Therapy designation. Koselugo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases, and Rare Pediatric Disease Designation for the treatment of pediatric NF1. The application is awarded a Rare Pediatric Disease Priority Review Voucher.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”

https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-children-debilitating-and-disfiguring-rare-disease

New Ebola case confirmed in the Democratic Republic of the Congo

0

April 10, 2020, WHO reported that a new case of Ebola virus disease was confirmed today in the city of Beni in the Democratic Republic of the Congo (DRC).

While not welcome news, this is an event we anticipated. We kept response teams in Beni and other high risk areas for precisely this reason,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General.

As part of the active Ebola surveillance system in place to respond to this ongoing outbreak in DRC, thousands of alerts are still being investigated every day. An alert is a person who has symptoms that could be due to Ebola, or any death in a high risk area that could have been as result of Ebola.

As with all confirmed cases, efforts are already underway to find everyone who may have been in contact with the person in order to offer them the vaccine and monitor their health status.

“WHO has worked side by side with health responders from the DRC for over 18 months and our teams are right now supporting the investigation into this latest case,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “Although the ongoing COVID-19 pandemic adds challenges, we will continue this joint effort until we can declare the end of this Ebola outbreak together.”

The news of the confirmed case came minutes after the conclusion of a meeting of the International Health Regulations Emergency Committee on Ebola in DRC. The Emergency Committee will reconvene next week in order to re-evaluate their recommendations in light of this new information.

Prior to this, the last person who was confirmed to have Ebola in DRC tested negative twice and was discharged from a treatment centre on 3 March 2020.

As of 10 April 2020, 3456 confirmed and probable cases and 2276 deaths have occurred as a result of the outbreak.
https://www.who.int/news-room/detail/10-04-2020-new-ebola-case-confirmed-in-the-democratic-republic-of-the-congo

Artificial Intelligence and COVID19

0

Let’s understand the AI:Artificial Intelligence (AI) can be described as the ability of a computer-controlled robot or digital device to perform tasks typically associated with intelligent beings. The concept is also applied to the project of designing structures endowed with the characteristic mental processes of humans, such as the capacity to think, to discover meaning, to generalize, or to learn from past experience “as per the Encyclopedia Britannica.

COVID-19 disease, caused by the SARS-CoV-2 virus, was detected in China in December 2019 and declared a global pandemic on 11 March 2020 by the WHO.

The new novel coronavirus, called SARS-CoV-2, had infected 735,560 patients worldwide as of March 30. The disease has caused more than 34,830 deaths to date, most often among older patients with underlying health problems, according to the World Health Organisation.

Artificial Intelligence (AI) is a potentially effective tool in fighting the pandemic COVID-19.

AI can be described as Machine Learning (ML), Natural Language Processing (NLP), and Computer Vision applications for present purposes to teach computers to use broad data-based models for pattern recognition, interpretation, and prediction.

Such functions can be useful in identifying (diagnosing), forecasting, and describing (treating) COVID-19 infections and assisting in controlling socio-economic impacts.

Since the occurrence of the pandemic, there has been a scramble to use and discover AI, and other data analytic tools, for these purposes.

The Artificial Intelligence (AI) tool has been shown to precisely predict which patients that have been newly infected with the COVID-19 virus would go on to develop severe respiratory disease.

Identifying vulnerable patients with AI:

The study has exposed the best indicators of future severity and found that they were not as expected.

Corresponding author Megan Coffee, clinical assistant professor in the Division of Infectious Disease & Immunology at NYU Grossman School of Medicine, said: “While work remains to further validate our model, it holds promise as another tool to predict the patients most vulnerable to the virus, but only in support of physicians’ hard-won clinical experience in treating viral infections.”

“Our goal was to design and deploy a decision-support tool using AI capabilities – mostly predictive analytics – to flag future clinical coronavirus severity,” says co-author Anasse Bari, PhD, a clinical assistant professor in Computer Science at the Courant institute.

“We hope that the tool, when fully developed, will be useful to physicians as they assess which moderately ill patients really need beds, and who can safely go home, with hospital resources stretched thin.”

Unexpected predictors:

Demographic, laboratory, and radiological findings of each subject tested positive for COVID-19 at the two Chinese hospitals in January2020 was recorded. Significant symptoms established over a week in a minority of patients like pneumonia.

The researchers decided to find out whether AI techniques could help predict precisely the patients with the virus will begin to develop Acute Respiratory Distress Syndrome or ARDS, the fluid buildup in the lungs that can be fatal in the elderly.

To do this, they have developed computer models that make decisions based on data fed into them, with more data being considered by programs being “smarter.” Specifically, at each step in a process, the current study used decision trees that track series of choices between options and model the possible consequences of choices.

The AI method found that changes in three functionalities – levels of the liver enzyme alanine aminotransferase (ALT), documented myalgia, and rates of haemoglobin – were most reliably predictive of subsequent serious illness. The team reported being able to predict ARDS risk with an accuracy of up to 80 percent, along with other variables.

ALT rates, which increase dramatically in patients with COVID-19 as diseases such as hepatitis damage the – liver, were only marginally higher, but still featured prominently in severity prediction. Furthermore, deep muscle aches (myalgia) were much more frequent, and were related to higher general inflammation in the body through past studies.

Eventually, higher levels of haemoglobin, were also associated with subsequent respiratory distress. Can this be clarified by other factors, such as unreported cigarette smoking, which has long been correlated with elevated rates of haemoglobin?

Of the 33 patients at Wenzhou Central Hospital interviewed on the smoking status, the two who reported having smoked, also reported that they had quit.

Limitations of the study, say the authors, included the comparatively small data set and the limited clinical severity of disease in the population studied.

“I will be paying more attention in my clinical practice to our data points, watching patients closer if they for instance complain of severe myalgia,” adds Coffee.

 “It’s exciting to be able to share data with the field in real time when it can be useful. In all past epidemics, journal papers only published well after the infections had waned.”

Actual and Potential Contributions of AI against COVID-19:

There are six areas where AI can contribute to the fight against COVID-19:

  • Early warnings and alerts
  • Tracking and prediction
  • Data dashboards
  • Diagnosis and prognosis
  • Treatments, and cures
  • Social control.

Early warnings and Alerts:

The case of BlueDot, the Canadian-based AI platform, has already become legendary. This shows that a fairly low-cost AI device (BlueDot was funded by a start-up investment of approximately US$ 9 million) can out-predict human outbreaks of infectious disease.

According to accounts, BlueDot expected the outbreak of the infection at the end of 2019 and released a warning to its customers on 31 Dec 2019, before the World Health Organization on 9 January 2020 did.

A note was also released by researchers working with BlueDot in the Journal of Travel Medicine on 14 January 2020, where it identified the top 20 destination cities where Wuhan passengers will arrive.

Although BlueDot is undeniably a powerful device, there is some distortion and some undervaluing of the role of human scientists in much of the attention it has earned.

Indeed, though BlueDot sounded an alarm on December 31, 2019, another AI-based application, HealthMap, sounded an alarm much earlier on December 30, 2019 at Boston Children’s Hospital in the USA.

In addition, a scientist at the Emerging Disease Monitoring System released an warning just 30 minutes after that. While the AI-based model was only 30 minutes quicker, it did add very low significance to the outbreak, however.

Essentially, identifying the danger involved human understanding and providing meaning. In addition, even in the case of BlueDot, humans remain central in assessing their performance, as explained in this podcast by Kamran Khan, Founder of BlueDot. Therefore it is rightly emphasized that human input is required for the optimal application of AI, and from various disciplines.

Tracking and Prediction

“AI can be used to track (including nowcasting) and to predict how the COVID-19 disease will extend over time and over space. For instance, following a previous pandemic, that of the 2015 Zika-virus, a dynamic neural network was developed to predict its spread. Models such as these will, however, need to be re-trained using data from the COVID-19 pandemic. This seems to be happening now. At Carnegie Mellon University, algorithms trained to predict the seasonal flu, are now be re-trained on new data from COVID-19.

Various problems bedevil the accurate forecasting of how the pandemic will spread. These include a lack of historical and unbiased data on which to train the AI; panic behavior which leads to “noise” on social media; and the fact that the characteristics of COVID-19 infections differ from those of previous pandemics. It is not only the lack of historical data but also the problems with using “big data,” e.g., harvested from social media, that have shown to be problematic.”

Here, the risks of big data and AI in the sense of infectious diseases, as seen in the notorious Google Flu Trends debacle, remain real.

During a 2014 paper during Science David Lazer, Ryan Kennedy and Alessandro Vespignani referred to these as “big data hubris and algorithm dynamics.” Of example, as the virus continues to spread and the social media traffic surrounding it accumulates, so accumulates the amount of noise that must be filtered through before clear patterns become discernible. For predictive tools based on past behaviour, Ian Rowan has described a global outlier event with its mass of new and unparalleled data such as COVID-19 as “the kryptonite of modern Artificial Intelligence approach” that will impact not only the prediction of infectious diseases but all predictive models, including those in finance, economics. As he explains, “many industries are going to be pulling the humans back into the forecasting chair that had been taken from them by the models”.

“One way to deal with big data hubris and algorithm dynamics is through content moderation on social media. The large social media platforms such as Google (YouTube) and Facebook have started to use AI more intensively to do content moderation, including checking for fake news, due to the reduction in human staff resulting from lockdown measures. Relying more on AI for content moderation has laid bare the fact that AI is still doing a poor job of it. YouTube admitted that using AI more extensively in content moderation is “error-prone.” This again illustrates the need for human input to, and direction of, AI.”

As a result of a lack of data, excessively much outlier data and noisy social media, big data hubris, and algorithmic dynamics, AI forecasts of the spread of COVID-19 are not yet very accurate or reliable.

Hence, so far, most models used for tracking and forecasting do notuse AI methods. As an alternative, most forecasters prefer established epidemiological models, so-called SIR models, and the abbreviation standing for the population of an area that is Susceptible, Infected, and Removed.

For example, the Institute for the Future of the Humanity at Oxford University provides forecasts of the spread of the virus based on the GLEAMviz epidemiological model. Metabiota, a San Francisco-based company, offers an Epidemic Tracker and a near-term forecasting model of the disease spread, which they use to make predictions. Tom Crawford, an Oxford University mathematician, provides a short and concise explanation of these SIR-models in a recent YouTube video.

The Robert Koch Institute in Berlin is using an epidemiological SIR model that takes into account government control steps, such as lockdowns, quarantines and prescriptions for social distancing.

A similarly expanded SIR model has recently been pre-published and made available in R format, taking into account public health initiatives against the pandemic and using data from China. In the case of China, the model of the Robert Kock Institute used earlier to demonstrate that containment can be effective in reducing the spread to slower than exponential levels.

Tracking and predicting the spread of the COVID-19 are important data inputs for public health authorities to plan, prepare, and manage the pandemic. And to evaluate where they are on the epidemiological curve and whether they succeed in flattening it. It can also provide rough reflection on the possible effect of measures taken to reduce or delay the spread.

For instance, the Robert Koch Institute predicted that by 28 March 2020 the number of infections in the Netherlands will reach 10,922. At this date, according to the CSSE of John’s Hopkins University, the overall number of patients infected in the Netherlands was 8647 lower than expected.

This may strengthen arguments that the government’s approach is helping to reduce the growth in infections.

Data Dashboards:

COVID-19’s monitoring and forecasting has contributed to the development of a technology dashboard industry that visualizes the pandemic. MIT Technology Review created a list of these Dashboards for monitoring and forecasting.

List the top dashboards as UpCode, NextStrain, JHU CSSE for the John’s Hopkins, Thebaselab, the BBC, the New York Times, and HealthMap. Many notable dashboards include an AI tracker for Microsoft Bing.

Diagnosis and Prognosis:

Fast and precise COVID-19 diagnosis will save lives, restrict disease spread and generate data to train AI models. In this regard, AI can provide useful feedback, especially with a medical diagnosis based on photographs. Studies have shown that AI can be as reliable as humans, save time for radiologists, and perform a diagnosis faster and cheaper than with standard COVID-19 tests, according to a recent study of AI applications against COVID-19 by researchers working with UN Global Pulse; You can use both the X-rays and the Computated Tomography (CT) scans.  Adrian Rosebrock offers a guide on how to use Deep Learning to use X-ray images to diagnose COVID-19. He points out that COVID-19 tests are “fast and costly, but all hospitals have machines with X-rays (or CTs).” Maghdid et al. (2020) suggested a technique for scanning CT images from cell phones.

The potential of AI in the diagnostics is not yet carried over into practice, although it has been reported that a number of Chinese hospitals have been deployed “AI-assisted” radiology technologies. Radiologists, conversely, have expressed their worry that there is not enough data available to train AI models, that most of the available COVID-19 images come from the Chinese hospitals and may suffer from selection bias, and that using CT-scans and X-rays may contaminate equipment and spread the disease further. Definitely, the use of CT scans in the European hospitals has dropped after the pandemic broke, perhaps reflecting this concern.

Finally, once the disease is diagnosed in the  person, the question is whether and how intensively that person will be affected, not all the people diagnosed with COVID-19 will need intensive care. Being able to estimate who will be affected more severely can help in targeting assistance and planning medical resource allocation and utilization. Researchers at China’s Huazhong University of Science and Technology have used ML in order to develop a prognostic prediction algorithm to predict the likelihood of somebody surviving the infection. And a team of the researchers from Wenzhou and New York prepared an AI that can predict with 80 percent accuracy which person affected with COVID-19 will develop acute respiratory distress syndrome (ARDS). The sample that they used to train their AI system is, still, small (only 53 patients) and restricted to two Chinese hospitals.

In conclusion, the application of AI to diagnose COVID-19 and to make a prediction of how patients will advance has stimulated a lot of work but is not yet widely operational. As Devan Coldeway concludes, “No one this spring is going to be given a coronavirus diagnosis by an AI doctor.” Also It seems that comparatively much less effort is on using AI for very early diagnostic purposes, for instance, in identifying whether someone is infected before it shows up in the X-rays or CT scans, or on finding data-driven diagnostics that have less contamination risk.

Treatments and Cures:

Long before the COVID-19 outbreak, AI had been lauded for its ability to lead to the development of new drugs. In the case of COVID-19, a number of research laboratories and data centers have reported that they are hiring AI to pursue care for and a COVID-19 vaccine. The expectation is that AI can accelerate both the processes of discovering new drugs as well as for repurposing existing drugs.

For example, Google’s DeepMind has predicted the structure of the proteins of the virus — information that could be useful in the development of new drugs. However, as DeepMind makes clear on its website, “we emphasize that these structure predictions have not been experimentally verified…we can’t be certain of the accuracy of the structures we are providing.”

South Korean and US researchers have reported results from the use of ML to classify an existing drug, atazanavir, that could potentially be repurposed to treat COVID-19. Researchers at the UK AI startup Benevolent AI and Imperial College published a paper in The Lancet describing Baricitinib, a drug used for rheumatoid arthritis and myelofibrosis, as a possible COVID-19 treatment. Researchers attached to the Singaporean firm Gero identified a variety of different experimental and licensed drugs using a deep neural network, including Afatinib, a lung-cancer medication that could theoretically be used to treat COVID-19. – But their paper was not peer-reviewed.

These therapies (and perhaps cures) are not very likely to be available in the immediate future, at least to be of great use during the current pandemic. The explanation is that, after these vaccines have been detected and tested, the medical and research tests, tracks, and controls that need to be carried out before they are licensed will take time for a vaccine according to estimates of up to 18 months.

Social Control:

AI has been, and can more be used, to manage the pandemic by scanning public spaces for the people potentially infected, and by enforcing social distancing and lockdown measures. For example, as described in the South China Morning Post, “At airports and train stations across China, infrared cameras are used to scan crowds for high temperatures. They are sometimes used with a facial recognition system, which can pinpoint the individual with a high temperature and whether he or she is wearing a surgical mask”.

Baidu, a Chinese firm, is one of the producers of these infrared cameras that scans crowds using computer vision. Such cameras are claimed to be able to scan 200 people per minute and identify those whose body temperature is above 37.3 degrees. Although, Thermal imaging has been criticized as being inadequate to identify from the distance a fever in people who are wearing glasses (because scanning the inner tear duct gives the most reliable indication) and because it cannot identify whether a person’s temperature is raised because of COVID-19, or some other reason.

More ominously, as the South China Morning Post further reports, “This system is also being used to ensure citizens obey self-quarantine orders. According to reports, individuals who flouted the order and left home would get a call from the authorities, presumably after being tracked by the facial recognition system.”

This use isn’t confined to China. A machine vision camera program focused on AI scanning public areas has been used to track whether people in the UK city of Oxford are adhering to the government’s social distancing initiativesA US computer-based vision company also provides “social distancing detection” software, which uses camera images to determine when social distancing norms are violated, after which a alert will be sent out.

In more severe situations, the Israeli government has approved cyber-monitoring to detect and quarantine people who may be compromised by its security services, and Russia is testing out a combination of an app and QR network to track infected people and manage movement.

When using AI to predict and diagnose COVID-19 is hindered by lack of historical training data, there are no AI resources like computer vision and robots. And in the short term, we are more likely to see this form of AI being used and used for social control in addition. Related technologies, such as mobile phones with AI-powered apps or wearables which harvest their owners’ location, usage and health data, are also more likely to be used . Georgios Petropoulos at Bruegel states that such apps “enable patients to receive real-time waiting-time information from their medical providers, to provide people with advice and updates about their medical condition without them having to visit a hospital in person, and to notify individuals of potential infection hotspots in real-time so those areas can be avoided.”

Google has made available “COVID-19 Group Mobility Studies” based on data from mobile devices, available for 131 countries, allowing one to analyze the effect of containment policies on the mobility of people.

Structure Identification:

Google DeepMind introduced AlphaFold which can predicts the 3D structure of a protein based on its genetic sequence. In March, this system was used to predict protein structure  several under-studied proteins associated with SARS-CoV-2,

University of Washington’s Institute for Protein Design  used computer models to develop 3D atomic-scale models of the SARS-CoV-2 spike protein. “Google’s machine-learning and data science platform Kaggle is hosting the Covid-19 Research Challenge, which aims to provide a broad range of insights about the pandemic, including the natural history; transmission and diagnostics for the virus; lessons from previous epidemiological studies; and more.“

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616181/ https://towardsdatascience.com/artificial-intelligence-against-covid-19-an-early-review-92a8360edaba?gi=dc137d7efa96
https://www.healtheuropa.eu/how-artificial-intelligence-is-helping-the-fight-against-covid-19/99258/