Category Archives: Gene therapy

An abnormality in the SOD1 gene is linked to some inherited cases of amyotrophic lateral sclerosis (ALS). So could turning off the mutated gene halt the disease? An international research team led by the University of California San Diego School of Medicine showed the potential of that strategy in mice by using a gene therapy approach.

A one-time injection of a gene-silencing RNA delivered by an adeno-associated virus (AAV) vector into the spinal cord prevented the onset of ALS in presymptomatic mice, and it blocked disease progression in rodents that had already developed symptoms. The team reported the findings in the journal Nature Medicine.

The SOD1 gene codes for an enzyme called superoxide dismutase. Normally, the enzyme breaks down superoxide radicals that are produced during cell metabolism. But in ALS, SOD1 mutations can create misfolded SOD1 protein, as toxic oxygen molecules persist, leading to the death of motor neurons.

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The UC San Diego-led team postulated that a short hairpin RNA (shRNA)an artificial RNA molecule that can silence gene expressioncould be utilized to block the dysfunctional SOD1 gene.

Other researchers had tried delivering shRNA-bearing vectors into the blood via intravenous injection. In mouse models of ALS, disease progression was indeed slowed, but the approach only extended survival by about three months. In a more recent study, scientists used intrathecal injection into the cerebrospinal fluid, but the animals lived only two months longer despite being treated immediately after birth.

For the current study, the UCSD researchers injected the shRNA-containing AAV therapy into the spinal subpial space at cervical and lumbar spine levels.

The team observed impressive results. Remarkably, SOD1-mutated mice treated before disease onset never developed disabilities related to motor neuron functions when followed to an average age of 462 days. That means they didn't lose functions like grip strength ororientation reflexes. The control animals, by contrast,started showing symptomsat about 306 days and reached the end-stage of ALS about three months later.

Further analysis showed that the therapy suppressed the accumulation of misfolded SOD1 protein and almost completely preserved motor neuron cells.

In mice that had already entered the symptomatic stage, the injection also blocked disease progression and further motor neuron degeneration, the team reported.

At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutatedSOD1gene-linked ALS, the studys senior author, Martin Marsala of UCSD, said in a statement.

RELATED:Biogen's antisense ALS drug shows promise in early clinical trial

Several other strategies have been developed aimed at decreasing the production of mutated SOD1 protein. Swiss biotech Neurimmune has a recombinant antibody called -miSOD1, which the company developed based on memory B cells that are found in healthy elderly people and that protect against misfolded SOD1. In mouse models of ALS, the drug extended the animals lives by up to two months.

Antisense oligonucleotide therapy isanother potential modality for fighting neurodegenerative disease. Biogen recently showed its antisense drug tofersen (BIIB067) was well tolerated in ALS patients in a small phase 1 study. At its highest dose, the drug cutSOD1 protein levels in spinal fluid and the patients performed well on certain clinical function tests.

Marsala and colleagues now plan to run additional studies of their spinal subpial shRNA approach in a large animal model to determine the optimal, safe dosage of the treatment.

In addition, effective spinal cord delivery of AAV9 vector in adult animals suggests that the use of this new delivery method will likely be effective in treatment of other hereditary forms of ALS or other spinal neurodegenerative disorders that require spinal parenchymal delivery of therapeutic gene(s) or mutated-gene silencing machinery, such as in C9orf72 gene mutation-linked ALS or in some forms of lysosomal storage disease, Marsala said in the statement.

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Halting ALS with a gene therapy approach - FierceBiotech

Home Topics Bleeding Disorders

BioMarin has submitted a Biologics License Application (BLA) to the Food and Drug Administration (FDA) for valoctocogene roxaparvovec (BMN 270) for the treatment of hemophilia A in adults. This is the first marketing application submission for a gene therapy product for any type of hemophilia.

Valoctocogene roxaparvovec is an investigational adeno-associated virus (AAV) gene therapy that is administered as a single infusion to produce clotting factor VIII. The BLA submission is supported by interim analysis of a phase 3 study and 3-year phase 1/2 data. Results from the ongoing phase 1/2 study showed that bleed rate control and reduction in factor VIII usage was maintained for a third year following a single administration of valoctocogene roxaparvovec.

The FDA previously granted Breakthrough Therapy and Orphan Drug designations to valoctocogene roxaparvovec. The Company anticipates the BLA review to commence in February 2020.

We look forward to working with the FDA as we seek marketing authorization for the potential first gene therapy for hemophilia A, said Hank Fuchs, MD, President, Global Research and Development at BioMarin. Our hope is one day very soon to deliver a transformative treatment that has the potential to change the way hemophilia A is treated.

For more information visit biomarin.com.

This article originally appeared on MPR

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BLA Submitted for Gene Therapy to Treat Hemophilia A - Hematology Advisor

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New York: A team of researchers report a novel approach in which three different gene delivery vectors were injected intravenously and directly into the kidneys of mice, rekindling hope to treat kidney diseases with gene therapy.

Before gene therapy can be used to treat renal diseases, delivery of therapeutic genes to the kidney must become much more efficient.

Jeffrey Rubin, Tien Nguyen, Kari Allen, Katayoun Ayasoufi, and Michael Barry from the Mayo Clinic co-authored an article published in the journal Human Gene Therapy.

As the kidney filters out large compounds from the bloodstream, the researchers chose to study the ability to deliver three different sized vectors via an intravenous route: small adeno-associated virus (AAV) vectors (25 nm), larger adenovirus vectors (100 nm) and lentiviral vectors (120 nm).

To bypass this filtering mechanism, they also tested two different direct injection routes into the kidney and found these to be superior to intravenous injections.

However, some of the vectors were able to leak out of the kidney, creating the possibility for off-target tissue effects.

The potential for direct injections opens new possibilities for treating kidney diseases with gene therapy, but additional improvements are needed, the authors wrote.

"The Mayo Clinic team has performed an important head-to-head comparison of currently available gene therapy technology, to identify which may best be used to address this important group of diseases," said Terence R. Flotte, Dean, Provost and Executive Deputy Chancellor, University of Massachusetts Medical School.

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Novel discovery in gene therapy to treat kidney diseases - Gulf News

Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrigs disease, is a neurodegenerative disease affecting nerve cells in the brain and spinal cord. Researchers at the University of California San Diego School of Medicine published research describing a new way to deliver a gene-silencing vector to mice with ALS. The therapy resulted in long-term suppression of the disease if the treatment was given before the disease started. It also blocked disease progression in the mice if symptoms already appeared.

The study was published in the journal Nature Medicine.

At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutated SOD1 gene-linked ALS, said senior author Martin Marsala, professor in the Department of Anesthesiology at UC San Diego School of Medicine. In addition, effective spinal cord delivery of AAV9 vector in adult animals suggests that the use of this new delivery method will likely be effective in treatment of other hereditary forms of ALS or other spinal neurodegenerative disorders that require spinal parenchymal delivery of therapeutic gene(s) or mutated-gene silencing machinery, such as in C9orf72 gene mutation-linked ALS or in some forms of lysosomal storage disease.

ALS appears in two forms, sporadic and familial. The most common form is sporadic, responsible for 90 to 95% of all cases. Familial ALS makes up 5 to 10% of all cases in the U.S., and as the name suggests, is inherited. Studies have shown that a least 200 mutations of the SOD1 gene are linked to ALS.

In healthy individuals, the SOD1 gene provides instructions for an enzyme called superoxide dismutase. This enzyme is used to break down superoxide radicals, which are toxic oxygen molecules that are a byproduct of normal cellular processes. It is believed that the mutations in the gene cause ineffective removal of superoxide radicals or potentially cause other toxicities resulting in motor neuron cell death.

The new research involves injecting shRNA, an artificial RNA molecule that can turn off, or silence, a targeted gene. This delivers shRNA to cells by way of a harmless adeno-associated virus (AAV). In the research, they injected the viruses carrying shRNA into two locations in the spinal cord of adult mice expressing an ALS-causing mutation of the SOD1 gene. They were performed just before disease onset or after the laboratory animals started showing symptoms.

The researchers have tested the approach in adult pigs, whose have spinal cord dimensions closer to those in humans. They found that by using an injector developed for adult humans, the procedure could be performed without surgical complications and in a reliable fashion.

The next step will be more safety studies with a large animal model.

While no detectable side effects related to treatment were seen in mice more than one year after treatment, the definition of safety in large animal specimens more similar to humans is a critical step in advancing this treatment approach toward clinical testing, Marsala said.

About 5,000 people are diagnosed with ALS in the U.S. each year, with about 30,000 people living with the disease. There are symptomatic treatments, but no cure. Most patients die from the disease two to five years after diagnosis.

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Experimental Gene Therapy Shows Promise for Preventing and Treating Lou Gehrig's Disease in Mice - BioSpace

For decades, the DNA of living organisms such as corn and salmon has been modified, but Crispr, invented in 2012, made gene editing more widely accessible. Image: YinYang/IStock.com via AFP Relaxnews

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering by editing her genome.

Victoria Grays recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research gene therapy.

I have hoped for a cure since I was about 11, the 34-year-old told AFP in an email.

Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency.

Over several weeks, Grays blood was drawn so doctors could get to the cause of her illness stem cells from her bone marrow that were making deformed red blood cells.

The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 pronounced Crisper a new tool informally known as molecular scissors.

The genetically edited cells were transfused back into Grays veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured.

This is one patient. This is early results. We need to see how it works out in other patients, said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville.

But these results are really exciting.

In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden.

For decades, the DNA of living organisms such as corn and salmon has been modified.

But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs.

The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself.

Its all developing very quickly, said French geneticist Emmanuelle Charpentier, one of Crisprs inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Cures

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy.

Scientists practicing the technique insert a normal gene into cells containing a defective gene.

It does the work the original could not such as making normal red blood cells, in Victorias case, or making tumor-killing super white blood cells for a cancer patient.

Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the United States and a blood disease in the European Union.

They join several other gene therapies bringing the total to eight approved in recent years to treat certain cancers and an inherited blindness.

Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution.

Twenty-five, 30 years, thats the time it had to take, he told AFP from Paris.

It took a generation for gene therapy to become a reality. Now, its only going to go faster.

Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a breakthrough period.

We have hit an inflection point, said Carrie Wolinetz, NIHs associate director for science policy.

These therapies are exorbitantly expensive, however, costing up to $2 million meaning patients face grueling negotiations with their insurance companies.

They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion and fighting a general infection.

You cannot do this in a community hospital close to home, said her doctor.

However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers.

They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Bioterrorism

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who dont necessarily share the medical ethics of Western medicine.

Last year in China, scientist He Jiankui triggered an international scandal and his excommunication from the scientific community when he used Crispr to create what he called the first gene-edited humans.

The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process.

That technology is not safe, said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr scissors often cut next to the targeted gene, causing unexpected mutations.

Its very easy to do if you dont care about the consequences, Musunuru added.

Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability.

There is also the temptation to genetically edit entire animal species malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US.

The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesnt believe in the more dystopian scenarios predicted for gene therapy, including American biohackers injecting themselves with Crispr technology bought online.

Not everyone is a biologist or scientist, she said.

And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies crops?

Charpentier thinks that technology generally tends to be used for the better.

Im a bacteriologist weve been talking about bioterrorism for years, she said. Nothing has ever happened.IB/JB

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2019: The year gene therapy came of age - INQUIRER.net

Home News Drugs in the Pipeline

BioMarin has submitted a Biologics License Application (BLA) to the Food and Drug Administration (FDA) for valoctocogene roxaparvovec (BMN 270) for the treatment of hemophilia A in adults. This is the first marketing application submission for a gene therapy product for any type of hemophilia.

Valoctocogene roxaparvovec is an investigational adeno-associated virus (AAV) gene therapy that is administered as a single infusion to produce clotting factor VIII. The BLA submission is supported by interim analysis of a phase 3 study and 3-year phase 1/2 data. Results from the ongoing phase 1/2 study showed that bleed rate control and reduction in factor VIII usage was maintained for a third year following a single administration of valoctocogene roxaparvovec.

The FDA previously granted Breakthrough Therapy and Orphan Drug designations to valoctocogene roxaparvovec. The Company anticipates the BLA review to commence in February 2020.

We look forward to working with the FDA as we seek marketing authorization for the potential first gene therapy for hemophilia A, said Hank Fuchs, MD, President, Global Research and Development at BioMarin. Our hope is one day very soon to deliver a transformative treatment that has the potential to change the way hemophilia A is treated.

For more information visit biomarin.com.

Please login or register first to view this content.

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BLA Submitted for Gene Therapy to Treat Hemophilia A - Monthly Prescribing Reference

Maximum Life Foundation ("MaxLife"), is rapidly transforming the way we treat aging diseases. MaxLife plans to use a promising gene therapy offered by Integrated Health Systems to give free access to ten (10) early to mid-stage Alzheimer's Disease (AD) patients. David Kekich, MaxLife's CEO, stated "MaxLife will grant 100% of the therapy costs to help bring pioneering gene therapy to cure this disease and make Alzheimer's Disease a thing of the past."

NEWPORT BEACH, Calif. (PRWEB) December 30, 2019

Cure Now Instead of Palliative Care

According to the Alzheimer's Association:

Alzheimer's costs Americans $277 billion a year and rising. Sharp increases in Alzheimer's disease cases, deaths and costs are stressing the U.S. healthcare system and caregivers. About 5.7 million Americans have Alzheimer's disease. To date, no one has survived it.

Improvements of AD symptoms and the recovery of normal brain functions have been demonstrated in-vivo in mouse experiments, and in-vitro in human cell experiments through the rejuvenation of microglia (the brain's first line of defense against infection) and neurons as well as stimulating mitochondrial function using the telomerase reverse transcriptase (TERT) protein.

One human patient received a lower dose therapy in August 2018 with no adverse side effects. To date, the patient's disease has not progressed. MaxLife hopes to see symptom reversals in the next patients.

"If we can prove a benefit to patients that have no other option now, we can potentially treat Alzheimer's Disease in people in early to mid-stage Alzheimer's, finally creating effective medicine at the cellular level," states Kekich. "If successful, this treatment could potentially be used on other diseases such as Parkinson's and ALS."

The unique difference is developing treatments against the cellular degeneration caused by aging as the root cause of most major diseases. Studies have proven aging is the leading risk factor for many life-threatening diseases, including Alzheimer's.

With a world class Scientific Advisory Board, MaxLife is ready to push forward into practical solutions. A gene therapy facilitator, Integrated Health Systems plans to treat other adult aging-related diseases with no previous cure such as Sarcopenia, Atherosclerosis, Chronic Kidney Disease (CKD) and even aging itself with gene therapies.

"This technology could halt many of the big age associated killers in industrialized countries'" states Kekich. "Compassionate care helps patients with no other option to get access to experimental therapies that may benefit both themselves and society as a whole."

MaxLife also seeks grants and donations for human gene therapy studies for atherosclerosis, sarcopenia and chronic kidney disease as well as for human aging. The protocols have already been developed. Please Click Here and scroll to the bottom of the page to see how to donate.

To apply for a free therapy or for more information, see http://www.maxlife.org/alzheimers-disease/ and https://maxlife.org/how-to-register-and-qualify-for-the-alzheimers-human-study/.

For Further Information, Contact: David Kekich, CEO Maximum Life Foundation.

Maximum Life Foundation is a 501(c)(3) Not-For-Profit corporation founded in 1999.

Tax I.D. #31-1656405. David A. Kekich Tel. #949-706-2468. Info@MaxLife.org

For the original version on PRWeb visit: https://www.prweb.com/releases/first_alzheimers_disease_gene_therapy_human_study_provided_by_maximum_life_foundation_offers_10_free_therapies_for_qualifying_patients/prweb16809113.htm

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First Alzheimer's Disease Gene Therapy Human Study Provided by Maximum Life Foundation, Offers 10 Free Therapies for Qualifying Patients - Benzinga

In the summer, a mother in Nashville with a seemingly incurable genetic disorder finally found an end to her suffering -- by editing her genome. Victoria Gray's recovery from sickle cell disease, which had caused her painful seizures, came in a year of breakthroughs in one of the hottest areas of medical research -- gene therapy. "I have hoped for a cure since I was about 11," the 34-year-old told AFP in an email.

"Since I received the new cells, I have been able to enjoy more time with my family without worrying about pain or an out-of-the-blue emergency." Over several weeks, Gray's blood was drawn so doctors could get to the cause of her illness -- stem cells from her bone marrow that were making deformed red blood cells. The stem cells were sent to a Scottish laboratory, where their DNA was modified using Crispr/Cas9 -- pronounced "Crisper" -- a new tool informally known as molecular "scissors." The genetically edited cells were transfused back into Gray's veins and bone marrow. A month later, she was producing normal blood cells.

Medics warn that caution is necessary but, theoretically, she has been cured. "This is one patient. This is early results. We need to see how it works out in other patients," said her doctor, Haydar Frangoul, at the Sarah Cannon Research Institute in Nashville. "But these results are really exciting." In Germany, a 19-year-old woman was treated with a similar method for a different blood disease, beta thalassemia. She had previously needed 16 blood transfusions per year.

Nine months later, she is completely free of that burden. For decades, the DNA of living organisms such as corn and salmon has been modified. But Crispr, invented in 2012, made gene editing more widely accessible. It is much simpler than preceding technology, cheaper and easy to use in small labs. The technique has given new impetus to the perennial debate over the wisdom of humanity manipulating life itself. "It's all developing very quickly," said French geneticist Emmanuelle Charpentier, one of Crispr's inventors and the cofounder of Crispr Therapeutics, the biotech company conducting the clinical trials involving Gray and the German patient.

Cures

Crispr is the latest breakthrough in a year of great strides in gene therapy, a medical adventure started three decades ago, when the first TV telethons were raising money for children with muscular dystrophy. Scientists practising the technique insert a normal gene into cells containing a defective gene. It does the work the original could not -- such as making normal red blood cells, in Victoria's case, or making tumor-killing super white blood cells for a cancer patient. Crispr goes even further: instead of adding a gene, the tool edits the genome itself.

After decades of research and clinical trials on a genetic fix to genetic disorders, 2019 saw a historic milestone: approval to bring to market the first gene therapies for a neuromuscular disease in the US and a blood disease in the European Union. They join several other gene therapies -- bringing the total to eight -- approved in recent years to treat certain cancers and an inherited blindness. Serge Braun, the scientific director of the French Muscular Dystrophy Association, sees 2019 as a turning point that will lead to a medical revolution. "Twenty-five, 30 years, that's the time it had to take," he told AFP from Paris.

"It took a generation for gene therapy to become a reality. Now, it's only going to go faster." Just outside Washington, at the National Institutes of Health (NIH), researchers are also celebrating a "breakthrough period." "We have hit an inflection point," said Carrie Wolinetz, NIH's associate director for science policy.These therapies are exorbitantly expensive, however, costing up to $2 million -- meaning patients face grueling negotiations with their insurance companies. They also involve a complex regimen of procedures that are only available in wealthy countries.

Gray spent months in hospital getting blood drawn, undergoing chemotherapy, having edited stem cells reintroduced via transfusion -- and fighting a general infection. "You cannot do this in a community hospital close to home," said her doctor. However, the number of approved gene therapies will increase to about 40 by 2022, according to MIT researchers. They will mostly target cancers and diseases that affect muscles, the eyes and the nervous system.

Bioterrorism

Another problem with Crispr is that its relative simplicity has triggered the imaginations of rogue practitioners who don't necessarily share the medical ethics of Western medicine. Last year in China, scientist He Jiankui triggered an international scandal -- and his excommunication from the scientific community -- when he used Crispr to create what he called the first gene-edited humans. The biophysicist said he had altered the DNA of human embryos that became twin girls Lulu and Nana.

His goal was to create a mutation that would prevent the girls from contracting HIV, even though there was no specific reason to put them through the process. "That technology is not safe," said Kiran Musunuru, a genetics professor at the University of Pennsylvania, explaining that the Crispr "scissors" often cut next to the targeted gene, causing unexpected mutations. "It's very easy to do if you don't care about the consequences," Musunuru added. Despite the ethical pitfalls, restraint seems mainly to have prevailed so far.

The community is keeping a close eye on Russia, where biologist Denis Rebrikov has said he wants to use Crispr to help deaf parents have children without the disability. There is also the temptation to genetically edit entire animal species -- malaria-causing mosquitoes in Burkina Faso or mice hosting ticks that carry Lyme disease in the US. The researchers in charge of those projects are advancing carefully, however, fully aware of the unpredictability of chain reactions on the ecosystem.

Charpentier doesn't believe in the more dystopian scenarios predicted for gene therapy, including American "biohackers" injecting themselves with Crispr technology bought online. "Not everyone is a biologist or scientist," she said. And the possibility of military hijacking to create soldier-killing viruses or bacteria that would ravage enemies' crops? Charpentier thinks that technology generally tends to be used for the better. "I'm a bacteriologist -- we've been talking about bioterrorism for years," she said. "Nothing has ever happened."

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Year in Review: Gene Therapy Technology and a Milestone 2019 for Medical Research - News18

Roche (OTCQX:RHHBY) has been quite busy in 2019 and it is apparent that it is making a hard push towards building a pipeline of gene therapies. This involves two major deals this year dealing specifically with gene therapy companies. Both of these were large ones, and it shows the commitment of Roche and many other big pharmaceuticals looking to make a move in this particular space. That's because of the potential to cure rare diseases using gene therapy. I believe that Roche has done well with its oncology pipeline over the years. It has been able to establish big blockbuster products in the cancer space like Herceptin, Avastin, and Rituxan. It seems to have made a good shift towards gene therapy as of late, which is evidenced by the large deals it had enacted.

The latest deal that was made by Roche was between itself and Sarepta Therapeutics (SRPT). Specifically, Roche received the rights to launch and commercialize Sarepta's gene therapy SRP-9001 outside of the United States. Roche is to pay an upfront cash payment of $750 million in cash and then about $400 million worth of equity. From there, Sarepta is eligible to receive up to $1.7 billion in regulatory sales and milestones, plus royalties on net sales of products. Sarepta will still pay for the cost of manufacturing and clinical development of the SRP-9001 candidate. Both Roche and Sarepta will share equal costs of global clinical development of the gene therapy.

The most important question to ask is why was Roche interested in gaining ex-US rights for SRP-9001? The first and foremost important reason is that it involves the potential for a one-off treatment or cure for DMD patients. The theory is that by using a micro-dystrophin gene therapy product, the patient would, in turn, achieve an improvement of dystrophin production. Any company that achieves such an outcome for DMD patients would pretty much take most if not the entire market. A second reason why Roche would get involved is because of the early clinical data shown to date. In a non-placebo controlled study with 4 patients, it was shown that there was a mean micro-dystrophin expression of 95.8%. Right away, it is important to note that a 4 patient sample size is not highly adequate to predict clinical outcomes for future trials. It is quite possible that a larger group of patients may not achieve a similar outcome.

On the flip side, the preliminary data does show that SRP-9001 is highly active in treating the disease. This is not shocking because of gene therapies making major strides in treating diseases, but for the fact that micro-dystrophin is being used. A typical dystrophin gene (DMD gene) is too large to have DNA of the gene encoded into the vector. Therefore, micro-dystrophin is a shortened version of the dystrophin gene necessary for DMD patients to have in order to improve muscle movement. Getting back to the vector, it is a differentiated type known as AAVrh74.

The point here is that AAVrh74 works in a much different manner compared to other gene therapies. Especially, those that utilize AAV9. A notable item to mention is that AAVrh74 is delivered to target cells with minimal immune response. It also does not cross the blood brain barrier. This point was proven in the 4 patient study where no serious adverse events ((SAEs)) were noted from treatment with SRP-9001. There were 3 patients who had elevated levels of gamma-glutamyl transferase (GGT). GGT is an enzyme found in the liver. The concentration of the enzyme rises when it is triggered by certain events. The micro-dystrophin gene therapy did cause this enzyme to elevate, but at the same time, the problem was immediately resolved when patients were given steroid therapy.

As I noted above, the type of vector AAVrh74 is likely a big reason why Roche got involved with Sarepta. Especially, when you dig deeper into the science of the vector. Specifically, it offers a MHCK7 promoter. What is the intended reason for having an MHCK7 promoter for SRP-9001? It is because if offers selective gene expression. By selective gene expression, it is inferred that the promoter drives expression to specific tissues that will likely benefit DMD patients. MHCK7 drives selective tissue expression in areas such as skeletal muscle, cardiac muscle, and diaphragm. All 3 of these areas are where dystrophin production is necessary for muscle movement.

It is my belief that Roche was highly impressed with the AAVrh74.MHCK7 vector itself that brought it to make such a large deal. In my opinion, it is a major advance in gene therapy, rather than the use of typical AAV9 vectors. Having said that, Roche also obtains the option of acquiring ex-U.S. rights to certain future DMD specific programs that Sarepta may yield at a later time. Yet again, this adds further potential for Sarepta to receive additional separate milestones, royalty payments and cost sharing for such other DMD programs. It is said that the licensing of SRP-9001 was one of the largest ex-U.S. gene therapy deal to date.

It is safe to say that the timing of this deal between Roche and Sarepta couldn't have come at a better time. Roche obtains ex-U.S. rights to the micro-dystrophin gene therapy and Sarepta obtains a lot of cash it can use towards developing its other products in its pipeline (including other gene therapies). Roche is the right partner in this regard because it has massive global reach to commercialize products. If and when SRP-9001 is approved, it will be rapidly dispersed because of the large commercial capability Roche has.

Having said all that, the deal made by Roche to acquire ex-U.S. rights for Sarepta's DMD gene therapy isn't the first deal done for this sector. Roche just recently completed its acquisition of Spark Therapeutics (ONCE). Roche announced that it would acquire the gene therapy company back in February of 2019 but has seen many delays since. The most notable reason for the delays was for regulators to make sure that the transaction wouldn't cause a monopoly or stifle competition in any way. This point is proven, where months ago, the US Federal Trade Commission (FTC) had requested information from both companies as part of review for the deal. In addition, the Competition and Markets Authority (CMA) wanted to review the deal as well. The CMA noted that the proposed deal could potentially reduce competition in the United Kingdom.

From Spark Therapeutics, Roche gains several prominent gene therapies. The biggest of which is Luxturna, which has already been approved by the FDA for an inherited form of vision loss. Specifically, in patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy which may lead to vision loss and complete blindness. The most likely acquisition for Spark was probably because of SPk-8011, which is being developed as a one-time treatment for Hemophilia A. This works well for Roche because it has already received FDA approval for one of its Hemophilia A drugs, known as Hemlibra. Hemlibra has done well on the market and it is expected that it could possibly generate as much as $5 billion in peak sales. If anything, SPK-8001 has the potential to become a one-off treatment. In my opinion, such a treatment option is something that these patients would highly desire over other treatments that require frequent dosing. Not only that, but it would protect Roche from competition in the Hemophilia A Space.

Roche seems to be making big bets in the gene therapy space. I will admit it is an exciting time for this sector, however, it doesn't come without notable risks. First and foremost, the biggest risk is pricing. That's because whether or not these gene therapy products survive in the market is highly dependent upon how they are priced. In addition, whether or not insurance carriers will cover the costs of the treatments. In the case of Novartis (NVS) with Zolgensma, it seems to be bucking the trend well so far, generating a solid quarter with $160 million in sales. Analysts only expected about $100 million, which was a huge surprise. Especially, since Zolgensma is priced at $2.1 million per treatment. As I have stated in prior articles though, such pricing can possibly be fixed by working with insurers. One such method is spreading out that $2.1 million price tag over a 5- or 6-year period. Thus, giving payers more incentive to cover the treatment. Roche may, hopefully, be able to fix such an issue with its partner Sarepta. In the case of Spark's Luxturna, it has not gone so well in terms of revenue. This will be a major problem for Roche because it will need to improve sales with this acquired gene therapy treatment. Another risk is the SPK-8011 gene therapy. That's because while the gene therapy was able to reduce the risk of bleeding events by 97% in 12 patients, it didn't do so without incident. There were 2 out of 7 patients who had an immune response issue and had seen Factor VIII levels to drop below 5% of normal when given the highest dose. One patient responded to oral steroids and the problem was resolved. The second patient didn't respond to oral steroids and had to go to the hospital to receive intravenous steroid treatment. Eventually, the second patient had responded to intravenous steroid treatment and was okay. The point here is that, while gene therapies acquired from ex-US rights for SRP-9001 along with the acquisition of Spark look promising, there is no guarantee that such products will reach the market.

I believe Roche made the right move in developing the ex-U.S. rights deal it did with Sarepta for SRP-9001. Especially, for the fact that the vector being used to deliver micro-dystrophin is quite unique compared to others. I also liked the way it set up the deal where it could have the option to obtain rights to certain future DMD programs. This would be other specific DMD programs in exchange for milestone payments/royalties type of a deal again. Lastly, I view these deals as being good for Roche as part of its commitment to help develop and commercialize therapies that improve the lives of patients with rare diseases. Based on the latest acquisitions of gene therapy companies it has achieved, I believe it is set up to do well in this sector for years to come.

This article is published by Terry Chrisomalis, who runs the Biotech Analysis Central pharmaceutical service on Seeking Alpha Marketplace. If you like what you read here and would like to subscribe to, I'm currently offering a two-week free trial period for subscribers to take advantage of. My service offers a deep-dive analysis of many pharmaceutical companies. The Biotech Analysis Central SA marketplace is $49 per month, but for those who sign up for the yearly plan will be able to take advantage of a 33.50% discount price of $399 per year.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Roche Finishes Year With Big Deals, Gene Therapy In Focus As Competition Heats Up - Seeking Alpha

For all the flak the pharmaceutical industry has taken for its exorbitant pricing practices, theres no getting around the fact that its been a pretty stunning decade for medical progress.

Multiple new categories of medicines have moved from dreams and lab benches into the market and peoples lives, and investors who came along for the ride often reaped extraordinary profits. The Nasdaq Biotech Index is up 360% over the last 10 years to the S&P 500s 190%. And thats without mentioning the hundreds of billions of dollars in takeovers that rewarded shareholders with windfalls.

As 2020 approaches, its worth highlighting how far weve come in the last decade in developing new therapies and approaches to treating disease, even as politicians grapple with how to rein in healthcare costs without breaking an ecosystem that incentivizes the search for new discoveries. Here are some of the decades biggest medical breakthroughs:

First approved in the U.S. two years ago, these treatments still sound like science fiction. Drugmakers harvest immune cells from patients, engineer them to hunt tumors, grow them by the millions into a living drug, and reinfuse them. Yescarta from Gilead Sciences Inc. and Novartiss Kymriah the two treatments approved so far can put patients with deadly blood cancers into remission in some cases. At the beginning of the decade, academics were just beginning early patient tests.

Its still in the early days for the technology, and some issues are holding these drugs back. There are significant side effects, and the bespoke manufacturing process is expensive and time-consuming. That has contributed to a bruising price tag: Both of the approved medicines cost over $350,000 for a single treatment. And for now, cell therapy is mostly limited to very sick patients who have exhausted all other alternatives.

Luckily, more options are on their way. Some drugmakers are focused on different types of blood cancers. Others hope to mitigate side effects or create treatments that can be grown from donor cells to reduce expenses and speed up treatment. In the longer run, companies are targeting trickier solid tumors. Scientists wouldnt be looking so far into the future without this decades extraordinary progress.

Researchers have spent years trying to figure out how to replace faulty DNA to cure genetic diseases, potentially with as little as one treatment. Scientific slip-ups and safety issues derailed a wave of initial excitement about these therapies starting in the 1990s; the first two such treatments to be approved in Europe turned out to be commercial flops.

This decade, the technology has come of age. Luxturna, a treatment developed by Spark Therapeutics Inc. for a rare eye disease, became the first gene therapy to get U.S. approval in late 2017. Then in May came the approval of Novartiss Zolgensma for a deadly muscle-wasting disease. The drugs have the potential to stave off blindness and death or significant disability with a single dose, and, unsurprisingly, Big Pharma has given them a substantial financial endorsement. Roche Holding paid $4.7 billion to acquire Spark this year, while Novartis spent $8.7 billion in 2018 to buy Zolgensma developer Avexis Inc.

Dozens of additional therapies are in development for a variety of other conditions and should hit the market in the next few years. They offer the tantalizing potential not just to cure diseases, but to replace years of wildly expensive alternative treatment. If drugmakers can resist the temptation to squeeze out every ounce of value by doing things like charging $2.1 million for Zolgensma, theres potential for these treatments to save both lives and money.

The above treatments modify DNA; this group uses the bodys messaging system to turn a patients cells into a drug factory or interrupt a harmful process. Two scientists won a Nobel Prize in 2006 for discoveries related to RNA interference, or RNAi, one approach to making this type of drug, showing its potential to treat difficult diseases. That prompted an enormous amount of hype and investment, but a series of clinical failures and safety issues led large drugmakers to give up on the approach. Sticking with it into this decade paid off.

Alnylam Inc. has been working since 2002 to figure out the thorny problems plaguing this class of treatments. It brought two RNAi drugs for rare diseases to the market in the last two years and has more on the way. The technology is also moving from small markets to larger ones: Novartis just paid $9.7 billion to acquire Medicines Co. for its Alnylam-developed drug that can substantially lower cholesterol with two annual treatments.

Ionis Pharmaceuticals Inc. and Biogen Inc. collaborated on Spinraza, a so-called antisense drug that became the first effective treatment for a deadly rare disease. It was approved in late 2016 and had one of the most impressive drug launches of the decade. And Moderna Therapeutics rode a wave of promising messenger RNA-based medicines to the most lucrative biotechnology initial public offering of all time in 2018. From pharma abandonment to multiple approvals and blockbuster sales potential in under 10 years. Not bad!

Scientists had been working on ways to unleash the human immune system on cancers well before the 2010s without much luck. Checkpoint inhibitors drugs that release the brakes on the bodys defense mechanisms have since produced outstanding results in a variety of cancers and are the decades most lucrative turnaround story.

Merck got Keytruda via its 2009 acquisition of Schering-Plough, but it was far from the focus of that deal. Once Bristol-Myers Squibb & Co. produced promising results for its similar drug, Opdivo, Merck started a smart development plan that has turned Keytruda into the worlds most valuable cancer medicine. Its now available to treat more than 10 types of the disease, and has five direct competitors in the U.S. alone. Analysts expect the category to exceed $25 billion in sales next year.

If anything, the drugs may have been too successful. Copycat efforts are pulling money that could fund more innovative research. There are thousands of trials underway attempting to extend the reach of these medicines by combining them with other drugs. Some are based more on wishful thinking than firm scientific footing. Still, the ability to shrink some previously intractable tumors is a considerable advance. If drugmakers finally figure out the right combinations and competition creates pricing pressure that boosts access, these medicines will do even more in the years to come.

From a combined economic and public-health standpoint, a new group of highly effective hepatitis C medicines may outstrip just about anything else on this list so far. Cure rates for earlier treatments werent especially high; they took some time to work and had nasty side effects. The approval of Gileads Sovaldi in 2013, followed in time by successor drugs such as AbbVie Inc.s Mavyret, have made hepatitis C pretty easily curable in a matter of weeks. For Gilead, getting to market rapidly with its drug proved enormously profitable; it raked in over $40 billion in revenue in just three years.

Hepatitis C causes liver damage over time that can lead to transplants or cancer. The existence of a rapid cure is a significant long-term boon even if the initial pricing on the drugs made them, in some cases, prohibitively expensive. Sovaldi notoriously cost $1,000 per pill at launch and over $80,000 for a course of treatment. The good news is that treatments have become a lot more affordable, which should allow this class of drugs to have a broad and lasting positive health effect.

Hepatitis C is one of the relatively few markets where the drug-pricing system has worked well. As competing medicines hit the market, the effective cost of these treatments plummeted. That, in turn, made the drugs more accessible to state Medicaid programs and prison systems, which operate on tight budgets and care for populations with higher rates of hepatitis C infection. Louisiana has pioneered the use of a Netflix model, under which the state paid an upfront fee for unlimited access to the drug. Its an arrangement that will help cure thousands of patients, and other states are expected to follow its lead.

Many of the medicines highlighted in this column have list prices in the six figures, a trend thats helped drive up Americas drug spending by more than $100 billion since 2009. Building on this decades medical advances is going to lead to even more effective medicines that will probably come with steeper prices.

Id like to hope that policymakers will come up with a solution that better balances the need to reward innovation with the need to keep medicines accessible.

That would really be a breakthrough.

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The 2010s were a decade of medical breakthroughs - Los Angeles Times