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Category Archives: Genetic Therapy
The brain’s imprint on the skull shows what separates humans from other primates – Massive Science
Scientists are trying to tackle the lack of diversity seen in genomics research, but even ambitious efforts, like the NIHs All of Us program, often fall short, especially when it comes to the inclusion of Indigenous communities. This is one of the reasons why the Decolonize DNA Day conference is taking place on April 24th, one day before the National DNA Day.
Traditionally, National DNA Day is an annual celebration of the discovery of DNA's double helix structure (1953) and the completion of the Human Genome Project (2003).
I was having conversations with colleagues on what would it mean to decolonize DNA, says Krystal Tsosie, an Indigenous (Din/Navajo) PhD student at Vanderbilt University. As an Indigenous academic, we always talk about what it means to Indigenize and re-Indigenize different disciplines of academia that have been historically more white-centred or white-dominated... and what it would mean to remove the colonial lens.
In collaboration with Latrice Landry and Jerome de Groot, Tsosie co-organized the Decolonize DNA Day Twitter conference to help re-frame narratives around DNA. Each speaker will have an hour to tweet out their "talk" and lead conversations on various topics, including how DNA ancestry testing fuels anti-Indigeneity and how to utilize emerging technologies to decolonize precision medicine.
There is a divide between people who are doing the science or the academic work, and the people who we want to inform, says Tsosie. Twitter is a great way to bridge that divide.
The Decolonize DNA Day conference is simply one effort to Indigenize genomics. Tsosie is also a co-founder of the Native BioData Consortium, a non-profit organization consisting of researchers and Indigenous members of tribal communities, focused on increasing the understanding of Native American genomic issues.
We dont really see a heavy amount of Indigenous engagement in genetic studies, which then means that as precision medicine advances as a whole [] those innovations are not going to be applied to Indigenous people, says Tsosie. How do we get more Indigenous people engaged?
Some of the answers can be found in a recent Nature Reviews Genetics perspective, penned by Indigenous scientists and communities, including those from the Native BioData Consortium. The piece highlights the actions that genomics researchers can take to address issues of trust, accountability, and equity. Recommended actions include the need for early consultations, developing benefit-sharing agreements, and appropriately crediting community support in any academic publications.
By switching power dynamics, were hoping to get genomic researchers to work with us, instead of against us, says Tsosie.
See the original post:
The brain's imprint on the skull shows what separates humans from other primates - Massive Science
Posted in Genetic Therapy
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Regenxbio Is A Leader In Gene Therapies – A Case Where The Platform Is Worth More Than The Pipeline – Seeking Alpha
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Regenxbio (RGNX) is a pioneer in gene therapies with a wide set of licensing agreements and an internal pipeline. The company focuses on adeno-associated virus (AAV) gene therapies for gene replacement and antibody delivery pursuing markets in retinal, neurodegenerative, and liver diseases. With a market cap of ~$1.3B (enterprise value of ~$1B), ~$400M of cash on the balance sheet, and ~$35M in revenue, Regenxbio is well-positioned to complete its milestones around manufacturing and clinical development into 2020.
The core investment thesis for Regenxbio is described below.
Validated technology platform to develop successful AAV gene therapies:
Strong financial position:
Undervalued internal assets:
From its 52-week high, Regenxbio's stock is down over 40%. The stock reached a low point from COVID-19 development. This is likely due to a lack of near term catalysts for the stock. With additional data for their lead asset in wet AMD coming in the first half of 2020, the initiation of phase II trials for the asset, and the sales ramp up for Zolgensma, the stock has a few potential catalysts coming up. As a result, there is an attractive entry point for investors to become an owner in Regenxbio.
Figure 1: RGNX daily chart (Source: Capital IQ)
The opportunity is that Regenexbio's licensing agreement with AveXis (NVS) on a medicine called Zolgensma to cure spinal muscular atrophy can potentially alone earn Regenxbio $3B-$4B in revenue. Zolgensma is an AAV gene therapy that delivers a transgene of SMN1 to cure the disease. About 20K people in the US have the disorder. With the medicine being priced at a little over $2M per patient, the market potential is well over $40B.
In 2014, Regenxbio licensed their AAV technology to AveXis to cure spinal muscular atrophy. The deal included various milestone payments to Regenxbio and importantly a mid-single to low double-digit royalties on net sales.
This one deal alone beyond the 20 similar deals Regenxbio has and its internal pipeline makes the company an attractive business. A simple DCF analysis with various assumptions, with the most important being including a capital expenditure of $400M for the clinical work with their flagship internal product, supports that Regenxbio is undervalued:
Figure 2: DCF model for RGNX (Source: Internal)
All the modeling done doesn't really help anyone figure out why this opportunity exists? Why is Regenxbio undervalued? Doubts around the Zolgensma scale up? Worries that capital from licensing deals will be wasted on an internal drug pipeline?
It's unprecedented that a drug company's platform is worth a lot more than the internal pipeline of drugs. From Regenxbio's latest corporate presentation, the company's main internal program, RGX-314, is focused on wet AMD:
Figure 3: Overview of Regenxbio's main asset (Source: Corporate Presentation)
RGX-314 is an AAV therapy for wet AMD. The slide describes the problem (leaky blood vessels in the eye) and how large it is (~2M patients) along with the vector (AAV8) and delivery cargo (anti-VEGF Fab). However, the company doesn't mention Eylea or other wet AMD medicines that are already approved. Regenxbio alludes to issues around delivery of drugs like Eylea (REGN), but doesn't go too deep on this slide or the presentation in general about how competitive their RGX-314 program will really be amongst clinicians.
An important point for any gene therapy is delivery whether it's a transgene or a CRISPR protein. A major reason why Regenxbio focused on wet AMD and ophthalmology in general is that delivering something to the eye is a lot easier than delivering something to the brain. RGX-314 is undergoing a phase I/II trial focused on establishing safety; the pivotal trial will come later. For the phase I portion, the company met their primary endpoint and showed safety so far. They have also shown how increasing doses of their gene therapy reduces the number of injections. This is going to be an important experiment and data set to argue for clinicians to switch over from something like Eylea.
The real value in Regenxbio is in its AveXis deal and the various licensing partnerships:
Figure 4: Regenxbio licensing partnerships (Source: Corporate Presentation)
Figure 5: Regenxbio licensing partnerships (Source: Corporate Presentation)
Figure 6: Regenxbio licensing partnerships (Source: Corporate Presentation)
This business model is enabled by Regenxbio's core technology focused on AAV7-10 and natural or close-to-natural variants:
Figure 7: Overview of Regenxbio's platform (Source: Corporate Presentation)
Over the next two years, the key milestones are:
The business can continue to strike up more licensing deals and expand current ones. The margin of safety here is that Regenxbio is undervalued just for its deal with AveXis and its various licensing deals that provide periodic payments based on progress and potentially more royalties if the drugs are approved and commercialized.
This seems to be a case where the market is focusing on the company's internal pipeline. Regenxbio's headline drug is interesting but unlikely to be competitive. Whereas, the business has a wonderful platform and licensing business that is being ignored. Simple valuations show these cash flows are not being fully appreciated. As a result, Regenxbio is going to grow revenue without any additional work and still has the potential to strike again through the 20 or so deals it has.
Figure 8: Key upcoming milestones for Regenxbio (Source: Corporate Presentation)
Regenxbio's lead candidate is focused on wet age related macular degeneration (AMD). The disease is a severe form of macular degeneration, a condition in which layers of macula get progressively thinner. The wet form is caused by abnormal blood vessels grown under the macula and retina where leaky blood vessels cause problems with vision, ultimately leading to blindness. The current standard-of-care is an anti-vascular endothelial growth factor (anti-VEGF) therapy. Patients require monthly injection of anti-VEGF to stop the growth of leaky blood vessels. Wet AMD is not a genetic disease, but it is a large and established market for Regenxbio to capture.
To frame the market opportunity of wet AMD, a few facts are helpful:
196 million people worldwide & 288 million by 2040 have AMD
10% have wet AMD, but is the leading cause of blindness
175,000 new patients annually in US
Growing number of patients due to aging population
Current treatments are regular injections of anti-VEGF
Figure 9: Overview of wet AMD (Source: JMS)
For wet AMD, competition comes from Genentech, Regeneron (REGN), and Adverum (ADVM). Genentech sells Lucentis at a price of $1850 per dose. Regeneron sells Eylea at $1150 per dose. Genentech's Avastin is also used off lab and is becoming more popular due to its cheap price of $60 per dose; the medicine is currently used for metastatic colorectal cancer. For gene therapies in wet AMD, the sole competitor is Adverum Biotechnologies. With 20M people with wet AMD, the total market opportunity for these medicines are in the billions of dollars.
Where Genentech's and Regeneron's medicines require multiple doses over the lifetime of a patient, a gene therapy has the potential to be curative and remove the multiple dosing requirement. For wet AMD, over 50% recurrence rate in the first year after treatment has stopped, and over 25% recurrence rate in the second year after treatment has stopped For drugs like Eylea and Lucentis, monthly intravitreal injection creates large burden for patients and create difficulty in dosing for clinicians. These problems allow Regenxbio to potentially capture the market with a gene therapy:
Figure 10: Wet AMD market (Source: Reportlinker)
Regenxbio's lead asset, RGX-314 is pursuing wet AMD. So far the company has shown:
Dose dependent protein expression levels and drug efficacy
Sustained protein expression for over 1.5 years
Long term efficacy demonstrated for Cohort 3 for rescue-free patients
No serious adverse events (SAE), but mild adverse events (AE) such as inflammation
Significant improvement in visual acuity for rescue free patients
Figure 11: Trial design of Regenxbio's lead asset (Source: Corporate Presentation)
RGNX
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Cohort 5
Dose
3 x 109 gc/eye
1 x 1010 gc/eye
6 x 1010vg/eye
1.6 x 1011 gc/eye
2.5 x 1011 gc/eye
Rescue Injection Free
Not Available
Mean 4.7 rescue inj.
Not Available
Mean 3.8 rescue inj.
3 / 6 Patients
Mean 1.3 rescue inj.
5 / 12 Patients
Mean 2.2 rescue inj.
9 / 12 Patients
Mean 0.8 rescue inj.
Duration
52 Weeks
52 Weeks
78 Weeks
52 weeks (2H 2020)
52 weeks (2H 2020)
Best Corrected Visual Acuity (BCVA)
In ETDRS letters
Mean: -2.0
Range: -8/+10
Mean: +7
Range: -4/+15
Mean: +8
Range: 0/+21
Mean: +2
Mean: +4
Central Subfield Thickness (m)
Mean: -14
Range -81/+92
Mean: +26
Range -7/+62
Here is the original post:
Regenxbio Is A Leader In Gene Therapies - A Case Where The Platform Is Worth More Than The Pipeline - Seeking Alpha
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Research Roundup: New Protein Linked to Alzheimer’s Identified and More – BioSpace
Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.
New Protein IDed that May Cause Alzheimers
Scientists at the University of Tokyo tested 19,151 individual genes looking for their effect on amyloid beta levels. Amyloid beta is one of the proteins that accumulates in the brains of Alzheimers patients and is generally viewed as one of the primary drivers of the disease. They identified a new protein using CRISPR/Cas9 gene editing, called calcium and integrin-binding protein 1 (CIB1). They found that cells without functional CIB1 genes generate abnormally high levels of amyloid beta protein. The research was published in FASEB Journal.
We believe this is the first time anyone has used this CRISPR/Cas9 genetic screening technique to look for changes in amyloid beta production, said Yukiko Hori, co-first author and lecturer at the University of Tokyo.
In normal, healthy cells, CIB1 is not directly involved with processing amyloid beta, but it stays attached to another protein, gamma secretase inside cells and at the cell membrane. In cells that dont have CIB1, gamma secretase stays inside the cell longer and doesnt leave the membrane. Amyloid beta undergoes multiple steps before reaching its final form. Normally, gamma secretase processes amyloid beta precursors to help produce the final amyloid beta protein. This happens inside the cell, then gamma secretase moves to the cells outer surface membrane.
Patients diagnosed with early-stage Alzheimers disease have lower levels of CIB1 in their brains, while people with late-stage Alzheimers have higher-than-healthy levels of CIB1.
We cannot say for certain why CIB1 is increased in late-stage Alzheimers disease, said Taisuke Tomita, who runs the research lab where the study was conducted. What is important is that in both the early and late stages of Alzheimers disease, something is abnormal about the regulation of CIB1.
Possible Approach to Improving Gene Therapy
Investigators at the University of Groningen have developed a technique that may improve gene therapies. They use DNA/lipid complexes (lipoplexes). Because the viruses used traditionally in gene therapies can cause an immune response and the cells endosomes tend to degrade DNA or other particles, the lipoplex provides protection. They can fuse with the endosome membrane, which prevents degradation.
Gene Promoters that Can Be Used to Treat Neurological Diseases
Researchers at Princeton Neuroscience Institute have developed new gene promoters that act like switches to turn on gene expression. They can be used in gene therapy, with a particular interest in neurological diseases such as Parkinsons and Alzheimers. Viruses are used to carry genes into cells during gene therapy, typically adeno-associated viruses. The Princeton team used promoters found in herpes viruses, which take up less space than existing promoters and allow the transport of larger genes or multiple genes. They are also long-lasting.
Biosensor to Detect SARS-CoV-2 in the Air
Researchers at Switzerland-based Empa, ETH Zurich and Zurich University Hospital have developed a sensor that has the potential to identify SARS-CoV-2, the novel coronavirus that causes COVID-19, in the air. The work is led by Jing Wang at Empa, who usually works on measuring and analyzing airborne pollutants. The sensor has reliably shown it can identify the first SARS-CoV virus that was responsible for the SARS pandemic in 2003. It has numerous similarities to SARS-CoV-2. Tests showed that the sensor can clearly distinguish between the very similar RNA sequences of the two viruses, Jing Wang said. And the results appear in minutes.
Possible Gene Therapy for Glaucoma
Glaucoma is a common condition of the eye involved fluid buildup in the front part of the eye. It affects more than 64 million people globally and is the leading cause of irreversible blindness. Current treatments include eye drops, laser or surgery. Researchers at the University of Bristol demonstrated that a single injection of a gene therapy using CRISPR and a gene called Aquaporin 1 targeting the ciliary body, where fluid is produced within the eye, led to reduced eye pressure.
More Evidence Parkinsons is an Autoimmune Disease
A study co-led by investigators at the La Jolla Institute for Allergy and Immunology (LJI) adds to the theory that Parkinsons disease is at least partly an autoimmune disease. The research was published in Nature Communications. Science has known for some time that the clumps of a damaged protein known as alpha-synuclein build up in the dopamine-producing brain cells of Parkinsons disease patients. The clumps lead to death of the cells and cause motor symptoms and cognitive decline.
Once these cells are gone, theyre gone, said Cecilia Lindestam Arlehamn, first author of the study and LJI research assistant professor. So if you are able to diagnose the disease as early as possible, it could make a huge difference.
A 2017 study showed that alpha-synuclein attracted certain type of T-cells, causing them to mistakenly attack brain cells, which potentially contributed to the progression of Parkinsons. The new findings found that the T-cells that react to alpha-synuclein are the most abundant when patients are first diagnosed with the disease. They tend to disappear later in the disease and by 10 years after diagnosis, few patients still have them.
This tells us that detection of T-cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet, said LJI professor Alessandro Sette, who co-led the research with David Sulzer of the Columbia University Medical Center. Importantly, we could dream of a scenario where early interference with T-cell responses could prevent the disease from manifesting itself or progressing.
See the rest here:
Research Roundup: New Protein Linked to Alzheimer's Identified and More - BioSpace
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On National DNA Day, scientists are trying to take the colonialism out of genetics – Massive Science
Scientists are trying to tackle the lack of diversity seen in genomics research, but even ambitious efforts, like the NIHs All of Us program, often fall short, especially when it comes to the inclusion of Indigenous communities. This is one of the reasons why the Decolonize DNA Day conference is taking place on April 24th, one day before the National DNA Day.
Traditionally, National DNA Day is an annual celebration of the discovery of DNA's double helix structure (1953) and the completion of the Human Genome Project (2003).
I was having conversations with colleagues on what would it mean to decolonize DNA, says Krystal Tsosie, an Indigenous (Din/Navajo) PhD student at Vanderbilt University. As an Indigenous academic, we always talk about what it means to Indigenize and re-Indigenize different disciplines of academia that have been historically more white-centred or white-dominated... and what it would mean to remove the colonial lens.
In collaboration with Latrice Landry and Jerome de Groot, Tsosie co-organized the Decolonize DNA Day Twitter conference to help re-frame narratives around DNA. Each speaker will have an hour to tweet out their "talk" and lead conversations on various topics, including how DNA ancestry testing fuels anti-Indigeneity and how to utilize emerging technologies to decolonize precision medicine.
There is a divide between people who are doing the science or the academic work, and the people who we want to inform, says Tsosie. Twitter is a great way to bridge that divide.
The Decolonize DNA Day conference is simply one effort to Indigenize genomics. Tsosie is also a co-founder of the Native BioData Consortium, a non-profit organization consisting of researchers and Indigenous members of tribal communities, focused on increasing the understanding of Native American genomic issues.
We dont really see a heavy amount of Indigenous engagement in genetic studies, which then means that as precision medicine advances as a whole [] those innovations are not going to be applied to Indigenous people, says Tsosie. How do we get more Indigenous people engaged?
Some of the answers can be found in a recent Nature Reviews Genetics perspective, penned by Indigenous scientists and communities, including those from the Native BioData Consortium. The piece highlights the actions that genomics researchers can take to address issues of trust, accountability, and equity. Recommended actions include the need for early consultations, developing benefit-sharing agreements, and appropriately crediting community support in any academic publications.
By switching power dynamics, were hoping to get genomic researchers to work with us, instead of against us, says Tsosie.
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On National DNA Day, scientists are trying to take the colonialism out of genetics - Massive Science
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Hydroxychloroquine, antibody therapy and antivirals: The coronavirus treatments being investigated and how long they might take – ABC News
Until recently you probably hadn't heard of hydroxychloroquine.
But suddenly the drug, which is used to treat malaria and inflammatory conditions such as lupus, was thrust into the spotlight when US President Donald Trump spruiked it as a treatment for coronavirus.
With a vaccine to prevent the disease at least 12 to 18 months away, and the death toll from COVID-19 mounting, scientists are scrambling to develop treatments.
Many of these drugs, like hydroxychloroquine, are already used for a range of other conditions, so they can be fast-tracked in development to go straight to large human trials.
Since the pandemic erupted, more than 1,500 research papers have been published, and there are hundreds of trials around the world.
But there is growing concern about the quality of research and how it is being interpreted, said Steven Tong, an infectious diseases expert at the Peter Doherty Institute.
"I've previously been an advocate of 'any data is good data', but just seeing what's happened in the past couple of months I'm revising that view," Dr Tong said.
"Some data and the way it's been presented can be very unhelpful in this kind of situation," he said, referring to the hype around the original hydroxychloroquine study that purported to show some benefit when the drug was used in combination with an antibiotic.
"People shouldn't have been making any efficacy claims about those treatments based on a really flawed study."
Many other studies are based on retrospective data from severely ill people who've recovered after being given unapproved drugs on compassionate grounds as a last ditch attempt to save their lives.
"It's where good peer review and well-designed and reported studies are what we should be aiming for," said Dr Tong, who heads up a team that will be conducting randomised controlled trials of hydroxychloroquine and some other drugs
Double-blind randomised controlled trials (RCT) are the gold standard of clinical research.
In these trials participants are assigned to either a control group, and given a placebo along with standard care, or a treatment group, where they are given the experimental drug along with standard care.
Neither the researcher nor the patient knows which group participants are assigned to.
So let's look at some of the treatments and what we do and don't know at the moment.
Chloroquine and hydroxychloroquine have been shown to stop coronavirus from entering cells under lab conditions.
Hydroxychloroquine has also been used for years to dampen the immune system in people with autoimmune conditions.
But Dr Tong said we don't know whether it could harm someone by dampening the immune system, which they need to fight off the illness, or if it will help someone who is severely ill from coronavirus because their immune system has gone into overdrive.
Hydroxychloroquine is known to affect the heart, which is why it should only be used in carefully controlled clinical trials, where patients are monitored, he added.
The problem with developing treatments, even those that have been used in other conditions, is that we don't know enough about the new virus or the immune response to it, said Larisa Labzin, an immunologist at the University of Queensland.
"One of the key things is that a lot of these drugs we find are going to be effective against the virus just in cells, [and] probably won't be that effective in the disease setting," Dr Labzin said.
"Really what we're looking for is not just that these drugs inhibit the virus replicating in people, but also that the people who get sick with the virus actually do better."
So far, there have been no large-scale high quality randomised controlled trials to demonstrate whether or not hydroxychloroquine is effective.
The latest study, which has not been peer-reviewed and is not a RCT, indicates it's not.
"We don't understand enough about what it's doing in the context of the whole disease, but it looks like it's not being very helpful at the moment," Dr Labzin said.
Another antiviral drug capturing headlines at the moment is remdesivir.
This experimental drug, which belongs to a family of drugs used to treat HIV and hepatitis C, targets an enzyme that the viruses use to copy their genetic code, known as a polymerase.
A bit like a Trojan horse, it inserts a molecule into the virus's RNA to stop it replicating.
Originally developed for Ebola, where it initially showed promise but eventually failed in trials, it showed some promise in the lab for treating SARS and MERS and now, the novel coronavirus.
Early compassionate use studies of remdesivir, given to patients with severe coronavirus infections, have been criticised for having no controls to see whether the results were due to the drug or if the patients would have improved anyway because of other factors.
Two randomised controlled trials were recently suspended in China, with one of those reportedly failing and having significant side effects, according to leaked documents that were posted on the World Health Organization drug trial database and then removed because the study was yet to be peer-reviewed.
The company behind the drug said the documents had "provided inappropriate characterisations of the study" and that it had been ceased due to low enrolment numbers.
"As such the study results are inconclusive," they said in a statement on Friday.
Scientists are now waiting for the results of large RCTs in the US and Europe.
Scientists such as Dr Tong are also looking at other drugs that treat HIV, including lopinavir-rotinavir.
Instead of targeting the virus's genetic code, these drugs target an enzyme the virus uses to chop up proteins.
"If you stop that protease from working then those proteins aren't chopped up the right way and it impairs the virus's ability to make more of itself."
This drug was shown to have a small effect in the lab and in case studies when it was used in Hong Kong for SARS, Dr Tong said, but the evidence is not strong enough at the moment to recommend widespread use.
With both approaches, there is also the possibility that the virus can identify the drugs and become resistant over time.
"We see that in HIV where we've learnt over the years that you have to use more than one drug to stop this resistance occurring," Dr Tong said.
"We haven't seen that yet [with SARS-Cov-2] but it's early days."
Instead of tinkering with the virus, antibody therapies aim to bolster the immune system's ability to recognise and neutralise the virus.
Antibodies are y-shaped molecules released by B-cells in the immune system that bind to the virus and alert other immune cells to come and kill them.
"These antibodies are generally quite long-lived and our immune system is good at pumping out loads of them," Dr Labzin said.
One treatment approach is to use antibodies in blood plasma from someone who has recovered from the disease.
Known as convalescent therapy or passive immunisation, this strategy has been used the past for Lassa fever, Ebola and swine flu, but most of the data is from case studies without controls.
Y-shaped antibodies released from immune cells stick to viruses and flag them to be killed
(Getty Images:)
Y-shaped antibodies released from immune cells stick to viruses and flag them to be killed
If specific antibodies can be identified, they can replicated in the lab. This strategy, known as monoclonal antibody therapy, is used to treat Ebola.
But we don't know enough yet about the antibodies: which ones work against coronavirus, how much you need or what will happen if you transfer them to other people.
"There have been a couple of preliminary trials ... but we need really big randomised trials to know if patients have recovered from the convalescent serum or whether they were going to just recover on their own," Dr Labzin said
There are a couple of large randomised controlled trials using this approach starting in the US and Canada, and it may also be an approach that is trialled in Australia by Dr Tong's team.
By the time someone becomes seriously ill with COVID-19, the problem may no longer be the virus, but the person's immune system going into overdrive, creating what is known as a cytokine storm.
"We don't really understand why it's uncontrolled in some people and not others," Dr Labzin said.
Her team plans to work on clinical trials for tocilizumab, an immunosuppressive drug that targets interleukin-6, a small protein or cytokine that has been implicated in inflammation and severe COVID-19 infections.
So far, there have been some studies of this drug, but they are based on data from patients after they've been given the drug and did not have any case controls.
University of Queensland researchers conduct experiments to design a vaccine for the coronavirus.
(Supplied: The University of Queensland)
University of Queensland researchers conduct experiments to design a vaccine for the coronavirus.
Supplied: The University of Queensland
Vaccines are the first line of defence in preventing an infection, but ultimately, one or more of these treatments will work alongside a vaccine as a back-up.
"There is the chance we won't have a successful vaccine," Dr Labzin said.
"Even if we do have a successful vaccine, sometimes we have problems with vaccinating particularly elderly people or immunocompromised people because they're no longer able to mount as good an immune response."
In that case, she said, the antiviral could work both as a treatment if they are diagnosed with coronavirus or as a prophylactic for high risk individuals.
Dr Tong hopes some of the questions around these therapies, such as hydroxychloroquine, will be answered in the next two to three months.
For now, the challenge is to find a treatment to reduce the risk of mortality of people who are severely infected.
Ultimately, however, he thinks there will never be a perfect treatment.
"What we're going to see is, we'll reduce the risk for severe complications ... but I suspect it's not going to be a massive difference.
"We're not suddenly going to halve someone's risk of mortality," he said.
"Even a reduction of 20 per cent in your risk of dying is still a significant and important impact. And if we can find an agent that can do that, that would be a great advance."
The only way to do that, he said, is to conduct rigorous clinical trials that provide a high level of evidence.
"At the moment it's easy for people to throw around treatments, but you don't learn anything from that and you don't learn what works and what causes harm rather than being of benefit."
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Hydroxychloroquine, antibody therapy and antivirals: The coronavirus treatments being investigated and how long they might take - ABC News
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FDA Approves Pemazyre as First Targeted Therapy for Cholangiocarcinoma – Cancer Health Treatment News
On April 17, the Food and Drug Administration (FDA) granted accelerated approval ofPemazyre(pemigatinib), a targeted therapy for the treatment of locally advanced or metastatic cholangiocarcinoma that carries a specific genetic mutation.
Cholangiocarcinoma is a rare cancer that forms in the bile ducts that carry digestive fluid from the liver to the gallbladder and small intestine. It is often detected at a late stage after it has started to spread and can no longer be surgically removed. Pemazyre is the first targeted therapy approved for this type of cancer.
The new kinase inhibitor, developed by Incyte, blocks fibroblast growth factor receptor (FGFR) types 1, 2 and 3. It is indicated for adults with previously treated, inoperable cholangiocarcinoma with FGFR2 gene fusions or other genetic rearrangements. The FDA also approved the FoundationOne CDx companion diagnostic test to screen for such mutations, which occur in around 12% of patients with cholangiocarcinoma.
With Pemazyre, we considered the observed efficacy results to be clinically meaningful and the overall risk-to-benefit assessment for patients with tumors harboring FGFR2 gene fusions and other rearrangements to be favorable, particularly when we considered that these patients have no other good options following first line treatment with chemotherapy, Richard Pazdur, MD, director of the FDAs Oncology Center of Excellence, said in a press release.
The approval was based on findings from the Phase II FIGHT-202 trial, which enrolled 107 people with locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements who had received at least one prior line of treatment. Study results were presented at the 2019 European Society for Medical Oncology Congress last fall and published in Lancet Oncology.
More than half of the participants were women, and three quarters were under age 65. All were treated with Pemazyre tablets once daily for 14 days, followed by seven days off, until they experienced disease progressed or unacceptable side effects. The trial was not randomized, and no one received a placebo or other treatment for comparison. Participants underwent scans every eight weeks to monitor cancer progression.
After a median follow-up of 15 months, the overall response ratemeaning complete or partial tumor shrinkagewas 36%, including 3% with complete remission. Another 47% had stable disease with no further progression. Among the 38 patients who responded, 24 (63%) had responses that lasted at least six months and seven (18%) had responses that lasted at least a year.
Overall survival results were still preliminary when the data were analyzed, but the median survival time of 21.1 months in this group far exceeded the 4.0 month duration seen in another patient cohort without FGFR2 fusions or rearrangements.
Treatment was generally safe and well tolerated. The most common adverse reactions observed in people taking Pemzyre were high or low phosphate levels, hair loss, diarrhea, constipation, nausea, vomiting, abdominal pain, decreased appetite, dysgeusia (abnormal taste sensations), nail problems, mouth sores, dry mouth, dry eyes, fatigue, joint pain and back pain.
The prescribing information for Pemazyre includes a warning about the risk of serious eye problems and recommends ophthalmological exams before and during treatment. Severely elevated phosphate levels (hyperphosphatemia) may also occur. Pemazyre can cause fetal harm if used during pregnancy.
Pemazyre received FDApriority review and breakthrough therapy designations, intended to expedite the development and review of medications for serious conditions that may offer substantial improvement over existing therapies. Medications that receive accelerated approval based on response rates are expected to undergo further testing in randomized trials to determine whether they improve progression-free or overall survival; the FDAcan rescind approval if they dont measure up. A Phase III study of Pemazyre versus standard chemotherapy is currently underway (ClinicalTrials.gov number NCT03656536).
Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,lead study investigator Ghassan Abou-Alfa, MD,of Memorial Sloan Kettering Cancer Center in New York, said in an Incyte press release. It is encouraging to have a new targeted treatment option for patients who historically have had limited options after first-line chemotherapy or surgery, in which relapse rates remain high.
Click here for full prescribing information for Pemazyre.
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