24 Feb 2020

Another gene therapy for a central nervous system disorder has posted positive results. The Phase 1/2 trial enrolled 18 men with X-linked retinitis pigmentosa (RP), a disease of retinal degeneration that leads to blindness. Robert MacLaren of the University of Oxford led the study, published February 24 in Nature Medicine.

The dose-escalation trialtested six doses; the therapy consisted of an adeno-associated virus 8 expressing a normal copy of the RP GTPase gene. Seven patients saw improvements in their vision that endured for the six-month duration of the trial. Inflammation within the eye cropped up at the higher doses, which may have temporarily blurred therapeutic effects in some patients.

Interest in using gene-based therapy for AD and other neurodegenerative disorders has grown ever since such a therapy was approved for treating spinal muscular atrophy (SMA) in babies and toddlers, and the field is now looking to learn from trials of other nervous system disorders (Nov 2019 news;Dec 2019 news).

X-linked RP is caused by mutations in the RP GTPase regulator (RPGR) gene. The mutations trigger degeneration of photoreceptors starting in childhood. No treatments exist. Recent approval of a gene therapy for another retinal disorderRPE65-related retinal degenerationsuggests retinal gene therapy could work (Russell et al., 2017).

However, the RPGR gene has confounded scientists, as it contains a repetitive, purine-rich stretch that undergoes alternative splicing. Tinkering with the sequence has boosted fidelity and stability of the gene, and conferred therapeutic benefits in animal models of the disease (Fischer et al., 2017).

In this trial, each of the 18 men, who were between 22 and 50 years old, had severe retinal degeneration. They were recruited in six cohorts of three patients each, who received increasing doses of the viral therapy. The participants received an injection of the virus into their subretinal space; they were then monitored for safetythe trials primary outcomeand tested for vision and retinal sensitivity for six months.

Across the cohorts, 55 adverse events occurred, all mild. Seven out of nine patients on the three highest doses experienced mild retinal inflammation, which was corrected by oral corticosteroids. In all, the trial met its primary safety endpoint.

Seven out of 12 patients receiving one of the top four doses had visual gains in the treated eye. This was gauged by retinal microperimetry, a map of the quality of light perceived across the retina. The improvements started at one month and continued at the six-month follow-up. The researchers proposed that inflammation in the top three dose cohorts may have offset visual improvements in some patients.

The trial was not designed to draw conclusions about efficacy. The researchers speculated that the therapys effectiveness will boil down to the stage of retinal degeneration, vector dose, and any interfering effects of inflammation. The second phase of the study will compare two doses to placebo.

Though the eyes are not strictly the brain, retinal therapy can be considered as part of the revitalization of gene-therapy approaches for neurodegenerative diseases. AAV-based expression of survival motor neuron 1 has improved life for those with SMA, but the tricky aspects of RPGE gene expression, and the inflammatory response that cropped up at higher doses, point to potential challenges other gene therapies may have to overcome (Nov 2016 news; Mendell et al., 2017).Jessica Shugart

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Retinal Gene Therapy Trial Posts Positive Result - Alzforum

In London, the firm Ori Biotech is developing an automated way to manufacture gene and cell therapies, a bottleneck for many biotech companies.

Mission: To develop a robotic system to automate the labor-intensive tasks involved in manufacturing cell and gene therapies, such as gene transduction and cell expansion.

Gene and cell therapies are maturing as a field, as advances in genomics and data analysis open up the way for ever more advanced therapies. One limitation of this trend is that much of the manufacturing process is currently manual, making it expensive and hard to produce consistent results.

The first generation of cell and gene therapies have demonstrated the revolutionary potential of these products but also the challenge of making them available to patients at scale, Ori Biotechs co-founder and CSO, Farlan Veraitch, told me.

Ori Biotech aims to address this manufacturing bottleneck by making robots take care of simple, but time-consuming tasks. For example, adding or taking away cells from cell culture containers in current practice is laborious, and also can also introduce contamination into the batch. Part of Oris approach is to make adjustable containers that reduce the need for moving cells between containers and exposing them to contamination.

There are many companies similarly developing methods for improving the manufacture of gene and cell therapies. For example, the Belgian company Univercells recently raised 50M to fund manufacturing technology to make viral vector production cheaper in gene therapies. Synthace is another company automating lab protocols involved in the quality control process of manufacturing. According to Veraitch, Ori stands out from other companies because it was set up by experts in the gene therapy field.

Many of them are startups innovating in one unit operation, others are part of established service providers that arent really technology companies and still others are repurposing technologies from other uses to try to find a way to fit a square peg to into a round hole, he told me.

Ori Biotech has a number of partners involved, such as Hitachi Chemical, and the UK innovation center Cell and Gene Therapy Catapult. The company aims to test its system in early 2020 in its partners labs. Ori is funding the development with an 8.6M seed round that it raised last month.

What we think:

With the current difficulties in manufacturing cell and gene therapies, they are expensive to make and arent meeting their full mainstream potential. With companies like Ori Biotech working on it, this may not be the case for long.

With the amazing clinical data coming through and more than 900 companies running more than 1,000 clinical trials in cell and gene therapy, the industry is poised at a tipping point, Veraitch said. We are seeing cures for previously untreatable types of cancer and terminal rare disease being studied and approved so there is plenty of reason to be hopeful.

In addition, Veraitch believes that overcoming manufacturing obstacles will also lead to the treatments becoming more accessible to healthcare systems and patients. At present, gene therapies are among the most expensive drugs in the world, such as Novartis spinal muscular atrophy treatment Zolgensma, which is priced at over 1.8M per person.

The industry is currently at a similar stage to Henry Ford building one Model-T at a time in his workshop and needs a move to the equivalent of assembly-line manufacturing, which would increase throughput, decrease costs, and increase quality, concluded Veraitch.

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This Startup Is Automating the Manufacture of Gene and Cell... - Labiotech.eu

A health ministry panel approved Wednesday the production and sale of a gene therapy for treating spinal muscular atrophy, a rare incurable disease that destroys muscle function through a decrease in motor neuron cells.

The health minister is expected to formally approve the drug, Zolgensma, by the end of March, with public health insurance coverage seen starting this summer.

The one-time-only gene therapy, developed by Swiss drug giant Novartis AG, will cover patients below 2 years old with abnormalities in their genes to make proteins necessary for maintaining motor nerves. Novartis estimates 15 to 20 children a year are likely to receive treatment using the drug in Japan.

In the therapy, proteins are created after the genes, carried by adeno-associated viruses, are delivered to motor nerves through intravenous drips. In an overseas clinical trial, all of the 15 severe SMA patients who used the therapy were able to live without an artificial ventilator. If no treatment is offered, about 75 percent of such patients are expected to die or need an artificial ventilator before they reach the age of 13.6 months.

The therapy, which has already been approved in the United States, is expensive, costing the dollar equivalent of 230 million for a one-time infusion.

See the article here:
Japanese government panel OKs expensive gene therapy for rare disease - The Japan Times

For the cell and gene therapy revolution to be fullyrealized, physicians, research scientists, biomanufacturing experts, advocacygroups, regulatory bodies like the Food & Drug Administration (FDA) andother key stakeholders have to Think Different, as Apple famously encouraged.

The vein-to-vein, one batch to one patientformula of personalized medicine is radically and rapidly forcing changes onbiomanufacturing where cell and gene therapy best practices are not yetcalcified and are changing as we speak. Personalized medicine supply chainchallenges are emerging and still being worked through and the high cost ofthese therapies remains a daunting challenge for life science companies andpatients.

Cell and gene therapy challenges across R&D, manufacturing, commercialization, and supply chain as well as bioethical challenges yet to be fully confronted or resolved have been well documented and discussed by experts across the BioHealth Capital Region (BHCR).

One company Jeeva InformaticsSolutions, Inc. (Jeeva) in Herndon, Virginia is developing BigData solutions for a less publicized but equally urgent cell and gene therapychallenge: How to manage a radically new form of clinical trial that could spandecades. Founder and CEO of Jeeva, Harsha K. Rajasimha, is building a companythat leverages Big Data, AI and mobile tech to decentralize clinical trials.Jeevas goal is to make it easier for biotech companies to collect, aggregate,analyze and report required clinical trial data while helping patients stayenrolled and compliant over longer periods of time with little travel from theconvenience of their homes.

The FDA recently passed newindustry guidelines requiring long-term follow up (LTFU) periods ofup to 15 years for gene and cell therapies, representing a sea change for howclinical trials will operate in the future.

The cell and gene therapy space provides significant hope for cures that can reverse genetic mutations. This space is growing. There are more than 900 clinical trials ongoing. Hundreds if not thousands of genetic diseases are likely to have therapies for the first time in our lifetime, stated Rajasimha.

At Jeeva, we are trying to solve a number ofissues but have focused on one particular problem that needs to be addressed ifthese cell and gene therapies are going to be delivered to patients: No oneknows the long term implications of these therapies because they are a one anddone type treatment. If a patient receives therapy today, they are done, and sothe FDA has mandated that recipients need to be monitored for up to 15 years.We are looking to address this issue with digital health technologies and AI,he added.

Jeeva believes that these long-term monitoringchallenges can be managed by making clinical trial participation easier viamobile applications, video conferencing consultations and centralizedscheduling, to name just a few of Jeevas product features. Leveraging digitalhealth tech can reduce the need for travel and eliminate inconveniences thatmight cause a patient to become non-compliant or, worse, drop out of a trialaltogether.

Decentralized clinical trials eliminate the heavy burden of patient travel and makes the process simpler and more efficient. Utilizing a Bring-Your-Own-Device (BYOD) approach and an eVisit consultation model to create decentralized trials can reduce brick and mortar visits by 20% to 80%, according to Jeeva.

Thenew FDA guidelines is the latest attempt to grapple with unchartedsafety protocols for cell and gene therapies. Clinical trial challenges are notnew to the biotechnology industry, however; rather, the approach to clinicaltrials has been inefficient and static for decades, leading to industry-wideproblems with clinical trial enrollment and recruitment that has a dominoeffect that lengthens the commercialization process and increases drugdevelopment costs.

We want to be a catalyst for accelerating thedrug development and delivery process. Patient recruitment is a huge barrierand has made the biopharmaceutical industry unsustainable. The average cost ofbringing a drug to market is $2.5B and takes 10-15 years to get to market. Wefeel that by educating and informing the global community about clinical trialsand enrollment opportunities using AI and digital health tech, we can help allstakeholders in getting people earlier access to treatments and getting thetreatments to markets faster, Rajasimha said.

Jeeva not only can help small to midsize biotechs improve trial recruitment and longer-term safety monitoring, but the company uses AI to improve clinical trial operations. By using AI and high tech tools, biotech companies can leverage historical trial data to shape new trials while empowering real-time adjustments to trials based on real-time monitoring to improve overall success rates.

Rajasimha continued, We have been building AItools to solve our customers specific needs, not just for AIs sake. Wesurveyed our customers last year and they told us Every single clinical trialseems like the first trial ever conducted by mankind. Even companies likePfizer and Novartis, which have been conducting hundreds of trials for decades,feel that when they launch a new trialit is no more efficient than theprevious trial.

So, we have been building an AI assistant that learns from past clinical trials data to make the next trial more efficient, he added. Rajasimha quickly reinforced patient centricity by saying it is not something you fix with an all technology solution, unless the robustly tested technology solution is combined with the human elements and focus on patients perspectives. Having been a global patient advocate in the U.S. over the past six years has given me a unique perspective on how to integrate technology in the lives of patients and caregivers. Moreover, a growing number of trials are recruiting patients from multiple countries and reducing international travel burden on patients over extended durations will be critical to achieve enrollment.

While the concept of virtual clinical trialsmight seem futuristic, Rajasimha and the Jeeva team believe the market is readyfor change.

A number of pilot projects or proof of concept clinical trials, about 20 of them, have been published where patients didnt go to the clinic at all. The feasibility of conducting such remote patients studies has been validated multiple times by the industry now. The tipping point has arrived. One of the key barriers for widespread adoption of decentralized clinical trials was a lack of FDA guidelines. Now the FDA has clarified its expectations about how the industry and stakeholders can share the responsibility to reduce the burden on patients. Enough validation and regulatory guidelines have put us in a position to give our customers what they need, stated Rajasimha.

Rajasimha sees partnering with smaller to midsize biotechs early on in the drug development process meaning well before the start of Phase II or III trials as an inflection point where it can deliver the greatest impact. In addition, we are seeing some initial interest from the Medical Cannabis industry, opioid crisis intervention for chronic pain management, and patient advocacy groups, where patients often live in remote, rural areas, can also benefit from decentralized, hybrid virtual clinical trials. Finally, real-world evidence studies, or longitudinal cohort studies, is also a growing market because companies need to collect and manage patients across longer time horizons, which is Jeevas sweet spot.

Rajasimha and Jeeva are starting to see this growing market interest manifest itself in new funding partnerships. Jeeva recently announced that CIT GAP Funds had invested in the company. Jeeva is currently in an early-stage investment round and the company is in active product development with a validated prototype. Jeeva is seeking new customer pilot projects to add to its ongoing pilots, which include chronic pain, medical cannabis, oncology and cell, and gene therapy products. Later this year, the company plans to complete multiple pilot projects and have validation in Good Clinical Practices (GCP) settings.

Rajasimha and his Jeeva team are certainlyembracing a think different approach to the future of clinical trials. Jeevaand its AI-driven, virtual clinical trial model is poised to help biotechcompanies thrive and meet the unmet medical needs of more patients across theglobe.

You can listen to Rajasimhas interviewwith podcast host Daniel Levine earlier this month on iheart radio here.

Team Jeeva is seeking customer pilot projectsand strategic partners to join the journey and will be exhibiting at the NationalInstitutes of Health Rare Disease Day event on Feb 28, 2020.Rajasimha will also be delivering a keynote speech on AI in rare diseases atthe BIO-IT World West Conference at San Franciscoon March 3rd, 2020.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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This Startup is on a Mission to Decentralize Cell and Gene Therapy Clinical Trials - BioBuzz

The excitement about cell and gene therapies is almost tangible within the biotech and pharma industry. Over 950 companies are actively developing advanced therapies, which are expected to make exceptional improvements to peoples lives in the next decade. Although hopes are high, the industry still faces a number of challenges in cell and gene therapy manufacturing, mainly around being able to deliver these often difficult to make, complex treatments at the scale needed to meet patient demand.

The unprecedented growth of the industry, alongside the need to develop scalable manufacturing strategies, has led to a number of challenges that need to be addressed urgently. Previously, patient numbers were so small that processes were highly manual and required numerous skilled operators. However, the recent success of early gene therapy trials means upscaling now needs to be considered right from the start.

In the early days the aim was just to get to the clinic, said Lindsey Clarke, Head of Cell and Gene Therapy EMEA at Bio-Techne. Scale didnt come into it so much, but now the conversations we are having focus much more on making these complex therapies at a scale needed for a commercial medicine. There are increased efforts on finding solutions that dont just work for trials with 10 patients, but will still work at 1000 times that scale.

Life science tools and technology provider, Bio-Techne, has made it its mission to further support the cell and gene therapy industry by channeling its expertise into developing technologies that can help to scale manufacturing processes. The companys commitment is highlighted by its recent investment into a new good manufacturing practice (GMP) manufacturing facility in St Paul, Minnesota, US, that will focus on producing raw materials for use in cell and gene therapy applications.

We have realized that if all our customers are to be successful with their therapies then there will be a huge demand for raw materials, Clarke explained. So weve started building that capability, ahead of time. But its not just about supply, we are also innovating, from simple things like looking closely at the format our products come in and making them more compatible with large-scale manufacturing to whole new product ranges.

Bio-Technes investment in the new GMP manufacturing facility is a solution to meet the growing demand for raw materials needed for cell and gene therapy manufacturing. But its just one piece of a large puzzle: cell and gene therapy developers also need to consider the complex logistics required to deliver their therapies to the clinic, particularly when its an autologous therapy.

The process from the patient to the clinician, to the apheresis collection, to the manufacturing site, then the complex manufacturing process and then delivery back to the patient is highly complex.

Another key challenge closely related to upscaling is the great risk of human error in manual processes. Many of the cell and gene manufacturing processes currently in place have been developed with small patient numbers in mind and involve manual steps.

Humans are an excellent source of variability and risk, explained Clarke. When youre manufacturing in a GMP environment, you need highly-skilled, trained operators and there is a shortage of them out there. Automation is going to be key to address this issue. Not only does it reduce the manpower that is required, but it can also streamline the processes and make them less risky, more scalable, and reproducible as well, Clarke added.

With cell and gene therapy products, various analytical methods are used to assess critical quality attributes during development and manufacturing. These reflect the identity, potency, purity, safety, and stability of the product. However, such methods are frequently complex, non-standardized, time-consuming, and performed manually by trained operators.

Organizations such as Cell and Gene Therapy Catapult have called for the development of new analytical solutions for quality testing of advanced therapies throughout the manufacturing process. More automated analytical technologies have the potential to increase facility throughput and make quality control (QC) faster, less error-prone, more reproducible, and more GMP compliant.

Although Bio-Techne has a long-standing history of developing quality proteins, antibodies, small molecules, and immunoassays, it has expanded into automated protein analytical technologies in recent years.

For viral and non-viral vectors, Bio-Technes ProteinSimple branded platforms are rapidly being adopted by cell and gene therapy developers for assessment of vector identity, purity, and stability. Compared to traditional methods like Western blot, SDS-PAGE, and ELISA, ProteinSimples technology platform is based on capillary electrophoresis and microfluidics and provides a fully automated and accurate quantitative analysis of vectors.

We are also seeing Micro-Flow Imaging (MFI), a more common image-based analytical platform in biologics, used to characterize subvisible particles for quality control of cell and gene therapy products, explained Kamar Johnson, Commercial Development Manager in Cell and Gene Therapy at Bio-Techne. These robust automated platforms offer ease of use, rapid time to result, and software that meets GMP requirements.

Collaboration lies at the heart of successful innovation. It is especially important at the interface between process development and manufacturing, said Johnson.

Not everyone is an expert in everything, we all have our particular niches of expertise, added Clarke. We believe that we need to collaborate to get the innovation that will help change the way we manufacture cell and gene therapies. Collaboration is the key to solving the challenges of the cell and gene therapy industry.

On that note, Bio-Techne recently partnered with Fresenius Kabi and Wilson Wolf to form a new joint venture that provides manufacturing technologies and processes for the development and commercialization of new cell and gene therapies.

The collaboration combines Bio-Technes expertise of proteins, reagents, media, and gene editing technologies with Fresenius Kabis Lovo cell processing system and the bioreactor expertise from Wilson Wolf with its G-Rex technology that is designed as a scalable platform for personalized cell therapies.

As processes develop and technologies evolve, the cell and gene therapy space will be confronted with new challenges. At Bio-Techne, the team is keeping an eye out for interesting trends that might affect the industry.

I see the induced pluripotent stem cell (iPSC) therapy field continuing to grow with more allogeneic cell therapies being developed, says Johnson. Allogeneic manufacturing is potentially less complicated than autologous manufacturing due to the ability to provide off-the-shelf products when patients need them.

Although the challenges in cell and gene therapy manufacturing remain a problem, companies like Bio-Techne are establishing quicker, simpler, and more automated options within quality control, manufacturing, and process development.

Wherever we go, we see newer technologies supporting cell and gene therapy manufacturing, says Clarke. Within our industry, changes come so rapidly and the treatments have shown so much promise that there is a lot of focus on cell and gene therapies. This puts a lot of pressure on us as an industry to provide these treatments. I believe that collaboration is the key to tackling this problem.

To learn more about the challenges in cell and gene therapy manufacturing and how to solve them, visit Bio-Technes website or get in touch with the experts here!

Images via Shutterstock.com

Author: Larissa Warneck

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Tackling the Challenges in Cell and Gene Therapy... - Labiotech.eu

The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them or one of the couple of Americans who arrived later got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

We dont have too much time, Andre Kalil, the trials lead investigator, told Endpoints News. Everythings moving really fast.

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Biogen touts new evidence from the gene therapy company it wagered $800M on - Endpoints News

AffyXell Therapeutics (South Korea), the recently established joint venture between biotherapeutics and reagents supplier Avacta and Korean pharmaceutical company Daewoong, (Jan 8) is now working under a collaboration and licensing agreement with Avacta for the generation of new cell and gene therapies.

The two companies will develop Avactas Affimer proteins against a range of targets which, when produced by mesenchymal stem cells (MSCs), are intended to inhibit inflammatory and autoimmune pathways and improve the overall efficacy of MSCs, creating a next generation of stem cell therapies.

The initial focus for AffyXell will be on inflammatory and autoimmune diseases. In the longer term, there is potential for AffyXell to address oncology uses for these Affimer-enabled cell and gene therapies.

Dr Alastair Smith, Chief Executive Officer of Avacta Group, commented: The potential for AffyXells new class of cell therapies, which can be applied to a wide range of inflammatory and autoimmune diseases, is enormous. We are therefore very excited by the opportunity to be part of this new venture and to demonstrate the power of Affimer proteins in the field of engineered cell therapies.

Seng-ho Jeon, CEO of Daewoong Pharmaceutical, commented: We are very excited to contract this Collaboration and License Agreement followed by the successful establishment of an innovative joint venture, AffyXell. Daewoong and Avacta will make every effort to (help) AffyXells growth and its development of distinguished and innovative cell and gene therapy treatment.

More:
Gene Therapies to Incorporate Enhanced Immune-Modulatory Effects - Labmate Online

For most parents, their child's second birthday is one of the many exciting milestones of toddlerhood - a chance to share a toast with friends and family and look forward to a future filled with possibilities.

For Queensland parents Kellee and Jamie Clarkson, it's a date that fills them with dread.

Their 18-month-old daughter Wynter has spinal muscular atrophy (SMA), a degenerative genetic disorder that attacks the motor neurons in her spine, progressively weakening her muscles and shutting down movement.

Without treatment, children like Wynter with type 1, the most severe form of the disease, will never sit up, crawl or walk and won't live to see their second birthday.

A revolutionary new gene therapy called Zolgensma is Wynter's best chance at a life free of wheelchairs, breathing apparatus and thrice-yearly lumbar punctures that leave her screaming for help but she only has until she turns two.

So far, the gene therapy is only available through health care in the United States, with Japan on Wednesday becoming the second country to approve the drug for children under two.

"It's such a long shot it would be like winning the lottery," Wynter's mum Kellee told 9News.

"But Jamie and I won't give up we will pursue every avenue we can."

The couple, who live just outside of Toowoomba, embarked on a fundraising drive last November in a desperate bid to raise the money, but the $66,000 they've raised falls far short of the jaw-dropping sum they need.

Their best hope now lies in a global lottery-style draw announced by drug's developers Novartis in December, offering 100 doses of the drug for free in 2020 to children under two years old.

But with roughly 60,000 children diagnosed worldwide every year, the chances of being drawn remain slim.

The first names have already been selected in a series of fortnightly draws, but the drug company is remaining tight-lipped on where the patients are located and how many children have missed out.

Swiss pharmaceutical company Novartis has attracted heavy criticism from patient advocates and health advisors for the lottery-style format of its global "managed access scheme".

UK patient group TreatSMA applauded the company's effort to offer the drug for free, but said it was "yet to be convinced that a health lottery is an appropriate way of meeting the unmet medical needs in this severe disease".

For parents, competing against other desperate families to gain treatment at the expense of others also comes at a psychological cost.

"It plays with your emotions," Kellee said.

"There are children worse off than Wynter and there are children better off. Wynter is older, she doesn't have as much time, so it would be hard to see a child who is much younger get it.

"It's so hard that there is such a big amount of money involved to give your child the best life, and it's just by chance that your child could get this drug."

Novartis' Director of Communications and Advocacy, Peter Murphy, defended the managed access program as "anchored in principles of fairness, clinical need and global accessibility".

He told 9News the company had sought advice from bioethicists as well as doctors and patient advocates before launching the program, and they had concluded this was the best way to ensure equity regardless of country of residence and capacity to pay.

With only one facility currently approved to manufacture the drug, they simply can't produce enough doses quickly enough to provide one to every child.

As they wait and hope for a miracle, life for the Clarksons centres around a gruelling schedule of daily physio exercises, fortnightly occupational therapy and speech therapy visits and the daily battle to keep Wynter from getting sick.

"Wynter can't sit on her own, she can't crawl, she obviously can't walk... She needs help with everything. I would do it to the day I die, but it's so hard to watch other kids be able to do those things," mum Kellee said.

As well as impacting gross motor skills, SMA can affect the muscles used for swallowing and breathing, meaning Wynter needs a BiPAP machine when she sleeps and finds the seemingly simple task of eating exhausting.

"We spend a lot of time trying to get her enough nutrition. It takes a lot out of her to eat it's like running a marathon," Kellee explained.

"Wynter at the moment is really struggling with her weight gain and it is a real possibility that she will have to have a gastric tube put in."

With SMA affecting Wynter's ability to cough and expel mucus, even going outside and playing with other children can have life-threatening implications.

"We're constantly worried about her getting sick. I'm constantly thinking about 'oh I don't want to go to the shopping centre because she could get a cold and die'," Kellee said.

That almost became a reality last year, when Wynter caught the common cold and ended up in ICU for two weeks fighting for life.

"She required lots of deep suctioning to the lungs, they put a catheter down her nose and mouth and she was on a BiPAP 24/7," Kellee said.

"It was the most traumatic, distressing experience of my life and my husband's."

Currently, the only medication available to treat SMA in Australia is Spinraza, a drug that has halted the devastating progression of Wynter's disease but has failed to give her back her compromised lung and swallowing functions.

It also means hospital visits every four months for the rest of her life.

"She's 17-months-old and she's had seven lumbar punctures," Kellee said.

"They can't give them any anaesthetic and she has to have it awake."

"It is absolutely horrendous to watch. As a parent, it just absolutely crushes you to see your child in pain and looking at you and wondering why you're allowing this to happen."

Patient advocacy group SMA Australia's Julie Cini said she understood the Clarkson's desperation to access Zolgensma, but the harsh reality was that some children would miss out while the drug was pending approval in Australia.

"It's like dangling a carrot in front of someone and then chucking it in the bin," she said.

Ms Cini is currently working to have the gene therapy approved under the Pharmaceutical Benefits Scheme, which would allow every child in Australia to access the drug.

Novartis applied to the Therapeutical Drug Administration in late 2019, but approval could still take many months, even years.

While paralysing her body, SMA has left Wynter's mind untouched, and Kellee says she remains a bright and bubbly toddler with a brilliant sense of humour.

"She has a very funny personality, she's very bright. A very happy little girl loves to dance, loves to laugh. She's at that stage where she's getting cheeky in a good way.

"She's got a powered wheelchair she drives around perfectly she doesn't know any different.

"To us, she's just perfect."

SMA advocate Ms Cini said it was important to remember just how far treatment had come.

She knows all too well the gut-wrenching trauma of watching your child's slowly but inevitable progress towards death.

"I look at Wynter every single day and I see what I couldn't see in my children," Ms Cini said.

"What she can do is phenomenal my kids couldn't do what she's doing. My outcome was death. The (Clarksons) have a chance to have a life with their child."

Ms Cini is optimistic that new treatments and early detection could see a future where those with SMA, even in its most severe form, could live long and independent lives.

A national newborn screening program to detect SMA before symptoms take hold vital in limiting the disease's progress - is currently being piloted in NSW.

"Hopefully, when drugs like Zolgensma get passed, we're able to treat our kids within the first two weeks of life," she said.

"I can see the future of SMA, I'm going to walk in to a room and I won't even know which kid has it."

For Kellee and Jamie Clarkson, that day can't come soon enough.

Read more from the original source:
Parents' fight to access life-changing $3.2m gene therapy for their daughter - 9News

The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them or one of the couple of Americans who arrived later got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

We dont have too much time, Andre Kalil, the trials lead investigator, told Endpoints News. Everythings moving really fast.

Unlock this story instantly and join 73,300+ biopharma pros reading Endpoints daily and it's free.

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'The headlines are the headlines, but': BioMarin talks up potential savings as hemophilia gene therapy launch looms - Endpoints News

Alia (2nd from left) and her father (left) with Dr Arif Khan (3rd from left), paediatric ophthalmologist and ocular geneticist at Cleveland Clinic Abu Dhabi, and other hospital doctors at a press conference in Abu Dhabi. Alia and her sister, Hessa, were the first to receive gene therapy in the UAE. Picture by Samihah Zaman, Image Credit:

Abu Dhabi: Two Emirati sisters from Abu Dhabi have become the first to receive gene therapy in the UAE, it was announced in the capital today.

The therapy was conducted with the aim of saving the vision of Alia, 13, and Hessa, 11, who suffered from retinal damage due to a defective gene.

The vision-saving surgery was performed at Cleveland Clinic Abu Dhabi in January (2020), and doctors said at a press conference that they are hopeful it will slowly improve the vision of both patients.

"The prospect of slowly losing one's vision from an untreatable condition is traumatic for both children and their parents. This genetic therapy means we can now replace the faulty gene in the eye, saving and even improving the vision of an individual who would otherwise have eventual irreversible blindness," said Dr Arif Khan, paediatric ophthalmologist and ocular geneticist at the hospital.

Only centre in region with procedure

Cleveland Clinic Abu Dhabi is only one of 10 centres worldwide, and the only one in the region, that is qualified to offer this procedure - the first gene therapy that was approved by the Food and Drug Administration in the United States, doctors said. But its availability opens the doors for more gene therapies to be offered to treat conditions as varied as diabetes and spinal muscular atrophy, they added.

Weve travelled abroad multiple times to find some treatment for our daughters, and this procedure has been a godsend. It has only been a month since the therapy however, and we are hoping for much more improvement to their vision over time, Fatima, the girls mother, told Gulf News.

The procedure

Alia and Hessa were born with RPE65-related retinal dystrophy, a genetic dystrophy in which the RPE65 protein is lacking because a child inherits two copies of the defective RPE65 from both parents. It is a recessive disease and therefore rare, and known to affect one in 200,000 people worldwide. But the condition is also more common in the region because of the limited genetic pool and cultural preferences for consanguineous marriages.

Patients with the condition face gradual damage to their retinas, the photosensitive layer at the back of the eye, and could eventually end up with irreversible blindness.

The gene therapy to treat the condition uses a vector - a bioengineered non-pathogenic virus to deliver normal copies of the RPE65 gene to the eye.

The procedure takes only about an hour, but it is very delicate. The retina can be considered an offshoot of the brain because its cells are very thin, like brain tissue. We use advanced microscopes to create openings in the white of the eye, then use a specialized canula to reach under the retina and inject the vector into the specific area, which can be as small as one-tenth of a millimeter, explained Dr Emad Abboud, chief of the department of the posterior segment at the hospitals Eye Institute.

Post-surgical recovery takes only about a week, but outcomes take a while to become obvious.

As Dr Khan explained, the main benefits for patients receiving the therapy is an improvement of vision in low-light conditions, and an improvement of the visual field.

Vision is a complex sense, involving photosensitivity, visual field, visual acuity, colour sensitivity, motion sensitivity, and the ability to navigate. But [at the least], this therapy prevents the progressive deterioration of the retina, he explained.

What the family said

My handwriting has definitely gotten better, Alia told Gulf News when asked about how the therapy has helped.

I cant tell what else will get better but I already feel that this has been life-changing, she added.

According to Fatima, she noticed her daughters had visual impairment when they were as young as two months old.

The doctor pointed out to me that they were not focusing or making eye contact. So we were aware of the condition. It definitely made life very challenging, especially as their development was delayed, the mother explained.

Alia and Hessa both crawled and walked late, and have needed assistance getting around. While they kept pace with their peers at school, it took Hercualean efforts from both girls, their parents, shadow teachers and at-home tutors, and required the use of Braille and visual aid resources.

Fatima and her husband, Mubarak, kept looking for treatments for both girls, travelling to Germany, India and Spain.

In 2016, we visited the Cleveland Clinic Abu Dhabi, and it was then that we heard of this revolutionary treatment. It was still not approved by the FDA, but we kept dreaming, she said.

It has been a month since the surgery and the doctors said they are more photosensitive now and that this is a good sign. Of course, as a mother, I would love for them to eventually have complete vision, Fatima added.

What is the therapy?

The UAE Ministry of Health and Prevention (MoHAP) approved the gene therapy for RPE65-related retinal dystrophy, Luxturna, in June 2019.

In a statement released at the time, the MoHAP said its registration of Luxturna was only the third global registration of the drug at the health authority level, and was aimed at paving the way for future gene-based therapies for complex conditions.

The United States Food and Drug Administration only approved Luxturna, developed by gene therapy developer, Spark Therapeutics, and the Childrens Hospital of Philadelphia, in late 2017.

The gene therapy to treat the condition uses a vector - a bioengineered non-pathogenic virus to deliver normal copies of the RPE65 gene to the eye with the defective gene.

While the Cleveland Clinic Abu Dhabi did not provide the cost of treatment, international media reports put it at $425,000 (Dh1.56 million) per eye.

Benefits of gene therapy

Dr Khan said at the press conference that us familiar with a few more families with the RPE65-related retinal disorder.

Over time, gene therapy could be used to treat many conditions. The eye is uniquely suited for these therapies because it is a self-contained organ. But at least five other genetic therapies are in development, some at the human trial level, he explained.

Consider gene delivery to be like providing a protein factory to the body. So for instance, some diabetic patients require regular insulin injections. If a gene could be engineered to make insulin, and it could be delivered to the patient, he wouldnt need these regular injections, Dr Khan added.

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UAE's first gene therapy improves eyesight of two Emirati sisters - Gulf News