Category Archives: Genetic Therapy

Biopsy results from the third patient dosed at 2E14 vg/kg in the SGT-001 IGNITE DMD clinical trial provide further support for continued development

Solid continues to make progress to address the IGNITE DMD clinical hold and advance the next steps for the SGT-001 program

CAMBRIDGE, Mass., March 12, 2020 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (SLDB) today reported financial results for the fourth quarter and full year ending December 31, 2019 and provided a business update. We are working to advance our lead program, SGT-001, a gene therapy candidate for Duchenne muscular dystrophy. We are pleased that biomarker data from all three patients dosed in the 2E14 vg/kg cohort of IGNITE DMD showed SGT-001 microdystrophin protein expression and associated neuronal nitric oxide synthase (nNOS) function, providing further evidence of the therapeutic potential of SGT-001. Our priority is to address the IGNITE DMD clinical hold so we can continue to evaluate the ability of SGT-001 to help patients with Duchenne, said Ilan Ganot, Chief Executive Officer, President and Co-Founder of Solid Biosciences.

Recent Developments

Financial Highlights

Research and development expenses for the fourth quarter of 2019 were $27.1 million, compared to $17.8 million for the fourth quarter of 2018. Research and development expenses for the year ended December 31, 2019 were $94.7 million, compared to $58.0 million for the year ended December 31, 2018. The increase was primarily attributable to compensation and other costs associated with additional headcount, as well as facility costs and increased expenses related to the clinical development and manufacturing activities for SGT-001.

General and administrative expenses for the fourth quarter of 2019 were $5.3 million, compared to $4.6 million for the fourth quarter of 2018. General and administrative expenses for the year ended December 31, 2019 were $24.6 million, compared to $17.7 million for the year ended December 31, 2018. The increase was primarily attributable to increased personnel costs.

Net loss for the fourth quarter of 2019 was $31.9 million, compared to $21.9 million for the fourth quarter of 2018. Net loss for the year ended December 31, 2019 was $117.2 million, compared to $74.8 million for the year ended December 31, 2018.

Solid had $83.5 million in cash, cash equivalents and available-for-sale securities as of December 31, 2019. Solid expects that it has sufficient capital to fund its operations into 2021.

In January 2020, Solid announceda reduction in workforce of approximately one third was implemented as part of a strategic plan designed to create a leaner company focused on advancing SGT-001. In connection with that, Solid curtailed its research and development activities supporting the company's complementary disease modifying and assistive device programs.

About SGT-001

Solids SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer therapy under investigation for its ability to address the underlying genetic cause of Duchenne muscular dystrophy (Duchenne). Duchenne is caused by mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase (nNOS). Data from Solids preclinical program suggests that SGT-001 has the potential to slow or stop the progression of Duchenne, regardless of genetic mutation or disease stage.

SGT-001 is based on pioneering research in dystrophin biology by Dr. Jeffrey Chamberlain of the University of Washington and Dr. Dongsheng Duan of the University of Missouri. SGT-001 has been granted Rare Pediatric Disease Designation, or RPDD, in the United States and Orphan Drug Designations in both the United States and European Union.

About Solid Biosciences

Solid Biosciences is a life science company focused solely on finding meaningful therapies for Duchenne muscular dystrophy (Duchenne). Founded by those touched by the disease, Solid is a center of excellence for Duchenne, bringing together experts in science, technology and care to bring forward meaningful therapies that have life-changing potential. For more information, please visit http://www.solidbio.com.

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Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding our expectations regarding the IGNITE DMD clinical trial, the safety or potential efficacy of SGT-001, the sufficiency of our cash, cash equivalents and investments to fund our operations and other statements containing the words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would, and similar expressions. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Solids ability to satisfactorily respond to requests from the FDA for further information and data regarding IGNITE DMD; successfully resolve the clinical hold with regard to IGNITE DMD; obtain and maintain necessary approvals from the FDA and other regulatory authorities and investigational review boards at clinical trial sites; enroll patients in its clinical trials; continue to advance SGT-001 in clinical trials; replicate in clinical trials positive results found in preclinical studies and earlier stages of clinical development; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; successfully scale its manufacturing process; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne treatments and gene therapies; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the Risk Factors section, as well as discussions of potential risks, uncertainties and other important factors, in the Companys most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Companys views as of the date hereof and should not be relied upon as representing the Companys views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

Investor Contact:Carlo Tanzi, Ph.D.Kendall Investor Relations617-337-4680investors@solidbio.com

Media Contact:Courtney HeathScient Public Relations617-872-2462media@solidbio.com

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Solid Biosciences Reports Fourth Quarter and Full Year 2019 Financial Results and Provides Business Update - Yahoo Finance

Familialhypercholesterolemia (FH) is one of the most clinically relevant monogenicdisorders contributing to the development of atherosclerotic cardiovasculardisease (ASCVD). The prevalence of FH was estimated to be 1 in 200 to 1 in 250 individualsin studies in which genetic testing was conducted on large community populationsamples.1 However, the disease often remains undetected and thusuntreated, with only 10% of individuals with FH receiving adequate diagnosisand treatment.2

Notingthe recent accumulation of studies on FH, the authors of a Nature ReviewsCardiology article sought tosummarize the key elements of a model of care for the condition that canbe adapted as new evidence emerges.1 Selected points are highlightedbelow.

Screening and detection. A combination of selective, opportunistic (eg, genetic screening of blood donors), systematic, and universal screening approaches is recommended to improve the detection of FH. Universal screening of children and childparent (reverse) cascade testing is potentially a highly effective method for detecting patients with FH at a young age, before they develop ASCVD32 [and] might be particularly relevant to communities with gene founder effects, noted the review authors. All children with FH should ideally be detected from the age of 5 years or earlier if homozygous FH (hoFH) is suspected.

Diagnosis. In the United States, elevated levels of low-density lipoprotein cholesterol (LDL-C) and a family history of FH are the main phenotypic criteria for FH diagnosis in children. Patients with hoFH, heterozygous FH (heFH), and polygenic hypercholesterolemia may also present with overlapping LDL-C levels, posing a challenge for the development of a standardized diagnostic tool for FH.

Genetic testing. Aninternational expert panel recently endorsed genetic testing in the care ofpatients with FH as it would [allow] a definitive diagnosis, improve[e] riskstratification, address the increasing need for more potent therapies, improve[e]adherence to treatments, and increase[e] the precision and cost- effectivenessof cascade testing.1,3 However, genetic testing remains underuseddue to issues such as cost, low access to genetic counseling, and lack ofclinician knowledge in this area.

Clinical risk assessment.Cumulative lifetime exposure to elevated LDL-C is the key factor driving ASCVDrisk in asymptomatic patients with FH, further underscoring the need for timelydiagnosis and risk stratification. In addition to phenotypic and geneticfactors, imaging of subclinical atherosclerosis, might be the most usefulclinical tool for assessing risk in FH.1 For example, imaging ofcoronary artery calcium can be used to predict coronary events in asymptomaticmiddle-aged patients with FH taking statins, and computed tomography coronaryangiography can be used to assess plaque burden and to intensify therapy.

Care of adults.Emerging evidence continues to support aggressive cholesterol-lowering therapyand lifestyle management in patients with FH from as young as 8 years tomaximally mitigate the cumulative cholesterol burden of risk. The review authorsemphasize the importance of patient-centered care and shared decision making,although health literacy is a challenge that may need to be addressed with somepatients.

Whilethere is insufficient evidence to develop strictly defined LDL-C treatmenttargets, current evidence-based recommendations stipulate that in adultpatients with FH, statin therapy and diet should initially be targeted toachieve a 50% reduction in LDL-cholesterol level and an LDL-cholesterol level<1.8 mmol/l (70 mg/dl) or <2.6 mmol/l (100 mg/dl) for primaryprevention, and <1.4 mmol/l (55 mg/dl) or <1.8 mmol/l (70 mg/dl) forsecondary prevention or for patients at very high risk.1

The addition of ezetimibe is indicated in patients who do not achieve the recommended LDL-C levels with statins alone. The use of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor as a third-line therapy is recommended in those patients or in patients who are intolerant to statins. The addition of a PCSK9 inhibitor in patients with heFH can further reduce LDL-C levels by approximately 60% and lead to recommended treatment targets in more than 80% of patients. However, these agents should not be used during pregnancy, as they cross the placenta and their impact on fetal development has not yet been determined.

Care of children. Extensive evidence supports the treatment of FH starting in childhood, as [m]odest and sustained reductions in LDL- cholesterol levels from early life can have a major effect on reducing mortality associated with ASCVD. Initial therapy is based on lifestyle management in early childhood, with the addition of statins by age 10 years in children with HeFH and upon diagnosis in children with hoFH. Ongoing research is investigating the efficacy and safety of PCSK9 inhibitors in children with heFH or hoFH.4,5

Radical therapies and novel approaches. Lipoprotein apheresis may be required insevere cases of FH, including in pregnant women, and liver transplantationremains the only curative therapy for patients with severe hoFH.

In ongoing studies, an array of novel treatment approaches are being examined, including functional LDL receptor gene transfer therapy in patients with hoFH and targeted RNA-based therapies to lower elevated lipoporotein(a) levels.6-8

Reviewauthors also emphasized the importance of clinical registries, patient supportgroups and networks, and the need for structured research programs that areunderpinned by actionable dissemination and implementation strategies,research skills and training among service providers, and sustainable fundingmodels. They stated that a major challenge is translating new evidence intohealth policy and routine care. Systems approaches for supporting healthorganizations and providers in addressing these gaps in care and serviceprovision are essential.

We spoke with Seth Shay Martin, MD, MHS, associate professor ofmedicine at the Johns Hopkins University School of Medicine in Baltimore,Maryland, and director of the Advanced Lipid Disorders Program of the Ciccarone Center atJohns Hopkins.

Cardiology Advisor: What are examplesof the latest advances in knowledge or practice pertaining to FH?

Dr Martin: A big advance inpractice has been the introduction of PCSK9 inhibitors. When added to statinsand ezetimibe, this class of medications can lower LDL-C by 60% sometimes the reduction can be lower, but inmy experience the effect is commonly approximately 60%. This leads to patientscoming back to clinic really satisfied.

Cardiology Advisor: What is the optimalapproach for the treatment of these patients, and what are some of the toptreatment challenges?

Dr Martin: The optimal approach is to follow the 2018 American Heart Association/American College of Cardiology multi-society guidelines, which recommend a combination approach of lifestyle modification with first-line maximal statin therapy, followed by the addition of ezetimibe and PCSK9 inhibitors. The LDL-C threshold at which additional therapy should be considered is70 mg/dL in high-riskpatients with ASCVD and FH. In patients with isolated FH (termed severe hypercholesterolemia by the guidelines,based on LDL-C levels 190 mg/dL), the LDL-C threshold is 100 mg/dL.

Cardiology Advisor: What are otherrelevant treatment implications for clinicians who treat these patients?

Dr Martin: One of the joys intaking care of a patient with FH is taking care of a family. It is a geneticdisorder with a 50% chance of being passed from parent to child. It is key toperform cascade testing to identify other members of the family; family visitsto the clinic can be beneficial for all.

Cardiology Advisor: What are remaining needs in thisarea?

Dr Martin: There is a great need for increasing awareness and diagnosis rates for FH. This is what our center is working to do as partners of the FH Foundation and as a CASCADE FH Registry site.

References

Read more from the original source:
Reviewing Evidence on the Screening, Diagnosis, and Care of Familial Hypercholesterolemia - The Cardiology Advisor

The bioindustry will require more cell and gene therapy plants, says an expert, who says the facilities of the future must be automated, scalable, and flexible.

The number of cell and gene therapies entering clinical development has increased significantly in recent years. According to the Alliance for Regenerative Medicines (ARM) there are 1,066 such therapies in trials at present1, which is a 32% increase on the number of studies in 2014. But the surge in clinical activity has not been matched by an increase in production capacity says Darren Dasburg, a cell and gene therapy-focused consultant.

Hundreds of facilities will be needed to manufacture the treatments that are in play now, he said, adding that if you factor in the plants needed to make viral vectors that could exceed a thousand facilities.

The good news, Dasburg says, is that these facilities are more like labs than traditional large biopharmaceutical plants.

Viral vector capacity is critical to the cell and gene therapy sector. Vectors are hollow viruses used to insert genetic material into cells, both cells used in protein expression and cells used therapeutically. Various organisations have voiced concerns about industry capacity to make vectors. In 2018, for example, the Alliance for Advanced Biomedical Engineering said the scarcity of viral vectors could hamper expansion2. Since then the situation has improved, but it has not been resolved3. While viral vector production capacity in the contract services sector has increased, the expansion is still falling short of demand.

Partly this is because of the complexity of making the vectors, according to Dasburg.

Most viral vectors are produced using adherent manufacturing technologies which are expensive to operate, he explains. A vial of just 20 million cells can cost $2030K because it is so challenging to make.

To bring down costs, vector capacity still needs to increase, continues Dasburg, who predicted that biopharma will continue to rely on CDMOs for the foreseeable future.

Cell and gene therapy manufacturing is still a young industry. Biopharma is still figuring out what the ideal production facility should look like.

Building for flexibility and multipurpose manufacturing is important, Dasburg says, noting that explaining CDMOs and IP holders need to understand they are attacking rare genetic diseases and ailments where the therapy might be a third-line treatment. The numbers are often quite lower, and the treatments can be one and done. All meaning the companies of the future will be attacking many more areas of need.

In terms of technology, all cell and gene therapy facilities should feature sufficient isolator capacity, Dasburg says. Isolators are probably the number one investment to make. Too many people are trying to work five people in full dress in a small room attempting to manufacture in a hands-on traditional way when isolation and automation could help immensely.

Dasburg pointed to benchtop platforms capable of processing a single CAR-T patients treatment as an example of an innovative approach being used. These can be arranged in an array within a single ballroom-like facility providing 100% containment going from leukapheresis bag to treatment bag without any human intervention.

References1. alliancerm.org/wp-content/uploads/2020/02/CBX-Meeting-7-Feb-2020-FINAL.pdf2. aabme.asme.org/posts/virus-shortage-for-cell-therapies-creates-engineering-opportunity3. http://www.genengnews.com/insights/gene-therapy-dollar-is-waiting-on-viral-vector-dime/

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More Cell and Gene Therapy Facilities in the Hundreds are Needed - Genetic Engineering & Biotechnology News

Newswise CLEVELANDResearchers at Case Western Reserve University have used a unique method to safely deliver gene therapy to fight a rare, but irreversible, genetic eye disorder known as Stargardt disease.

By using chemically modified lipidsinstead of the viruses most commonly used as carriersStargardt disease did not return in animal models for up to eight months after treatment, said lead researcher Zheng-Rong Lu, the M. Frank Rudy and MargaretDomiter Rudy Professor ofBiomedical Engineering at the Case School of Engineering, with a dual appointment at the School of Medicine.

Lus research, recently published in the journal Molecular Therapy, was funded in part through a Gund-Harrington Scholar grant, a partnership between Harrington Discovery Institute at University Hospitals and the Foundation Fighting Blindness.

This grant provides innovative scientists like Dr. Lu both funding and drug development expertise to advance research that will defeat diseases that limit millions of people from experiencing the gift of sight, said Jonathan S. Stamler, MD, President, Harrington Discovery Institute and Robert S. and Sylvia K. Reitman Family Foundation Distinguished Chair of Cardiovascular Innovation at University Hospitals and Case Western Reserve University School of Medicine. It is very encouraging to see Dr. Lus work move closer to human trials.

A so-far incurable disorder

The research may give some hope to people with Stargardt disease, an inherited disorder of the retina also known as macular dystrophy or juvenile macular degeneration because it often surfaces during childhood or adolescence.

Although individuals with Stargardt disease rarely go completely blind, they progressively lose vision in both eyes, become very sensitive to light and, in some cases, develop color blindness.

Were really excited because there is a potential to help people with Stargardt, Lu said. But we believe this success could also apply to other disorders as a platform therapy for delivering other genes through the use of the lipids.

Lipids are simple organic compounds, or fatty acids, that are insoluble in water, including various natural oils, waxes and steroids.

Because they are basically unsaturated oil, the likelihood of damage to the eye is low, which isnt always true with the viral gene therapy, Lu said.

Gene therapy offers best hope

There are a lot of researchers trying to figure out how to treat this disease right now with little success, Lu said. The best hope is gene therapy.

Gene therapy is the technology in which genetic material is introduced into cells by an engineered carrier to compensate for abnormal genes or to make a beneficial protein.

The most successful gene therapy carriers so far have been certain viruses (the AAV, or adeno-associated virus, especially) because they can deliver the new gene by infecting the target cell.

But the Stargardt-associated gene, known as the ABCA4 gene, turns out to be too large to fit within that popular virus, Lu said.

Lu said other researchers have attempted to remedy that problem by splitting ABCA4 into pieces and then trying to reassemble it inside the eyewith limited success.

Other researchers have modified a larger virus to carry ABCA4 into the eyes, a technology tested in human trials as far back as 2011, but which still hasnt been fully commercialized.

He said he and his collaborators have also already met with investors to expedite the commercialization of the platform used for Stargardt.

Further, this gene therapy product could be classified as an orphan drug by the U.S. Food and Drug Administration (FDA) because Stargardt is a rare disease, increasing the likelihood of faster FDA approval after clinical trials, Lu said.

The non-viral gene therapy is also much more cost-effective for production than the virus-based therapy and has a potential to significantly reduce the high price of gene therapy in the eye, he said.

We think that within two to three years we could really be helping people after further demonstration of its safety and efficacy, Lu said.

MEDIA CONTACTS:

Michael Scott, Case Western Reserve University

216.368.1004, mike.scott@case.edu

Carly Belsterling, University Hospitals

412.889.8866, carly.belsterling@uhhospitals.org

###

Case Western Reserve University

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,100 undergraduate and 6,200 graduate students comprise our student body. Visit case.edu to see how Case Western Reserve thinks beyond the possible.

Harrington Discovery Institute

The Harrington Discovery Institute at University Hospitals in Cleveland, OHpart of The Harrington Project for Discovery & Developmentaims to advance medicine and society by enabling our nations most inventive scientists to turn their discoveries into medicines that improve human health.The institute was created in 2012 with a $50 million founding gift from the Harrington family and instantiates the commitment they share with University Hospitals to a Vision for a Better World.

The Harrington Project for Discovery & Development

The Harrington Project for Discovery & Development (The Harrington Project), founded in 2012 by the Harrington Family and University Hospitals of Cleveland, is a $300 million national initiative built to bridge the translational valley of death. It includes the Harrington Discovery Institute and BioMotiv, a for-profit, mission-aligned drug development company that accelerates early discovery into pharma pipelines. For more information, visit:HarringtonDiscovery.org.

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Scientists successfully test new way to deliver gene therapy - Newswise

Gene therapy has become a powerful instrument for the treatment of many diseases to prevent or stop the disease from progressing.

Dr. George Aslanidi, Associate Professor and head of the Molecular Bioengineering and Cancer Vaccine lab at The Hormel Institute, University of Minnesota, received an award of $670,000 by the Minnesota Partnership for Biotechnology and Medical Genomics along with collaborator Dr. Kah-Whye Peng, Professor of Oncology at Mayo Clinic. They will work together to provide support for clinical applications of gene therapy in the effort to ensure novel cutting-edge technologies are available for patients.

Gene therapy aims to alter what nature has planned in an effort to change the outcome to a more positive one for patients, said Dr. Aslanidi, who joined The Hormel Institute in 2017. Manipulation of genetic materials such as gene substitution, gene overexpression, or gene editing can stop or alter what was destined to be negative for a patient and turn that around for a better life quality.

Adeno-associated virus (AAV) is a non-pathogenic human parvovirus that has been most widely explored as a virus-based delivery platform for safe and effective gene therapy of numerous inherited or acquired diseases affecting different organs/tissues. The recent success of AAV-based gene therapy for rare eye disease and muscular atrophy sparks interest for use vectors for wide-verity if genetic and other diseases when positive clinical outcome requires genetic manipulation with cell and tissues.

One of the major limitations in AAV technology applications is the bottleneck caused by the current production process and pre-clinical evaluation of the vector purity and activity. The current collaborative proposal between Dr. Aslanidi (The Hormel Institute, University of Minnesota) and Dr. Peng (Mayo Clinic) will provide access of researchers from both institutions to the reliable source of AAV for pre-clinical application produced under Good Laboratory Practice (GLP) principles to ensure safety, consistency, and quality of vectors. The ultimate goal of this study will be to provide patients with expanded, innovative cures.

The three-year grant begins in April 2020. The Minnesota Partnership for Biotechnology and Medical Genomics is funded by the Minnesota State Legislature and funds joint projects between University of Minnesota and Mayo Clinic in an effort to fund novel applications of advances in biotechnology, genomics, proteomics, imaging, bioinformatics and more in an effort to prevent, diagnose or treat disease to support and protect human health.

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$670000 gene therapy partnership grant for The Hormel Institute - Austin Daily Herald - Austin Herald

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.

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Parents' fight to access life-changing $3.2m gene therapy for their daughter - 9News