New Online Patient Education Program on Gene and Cell Therapies Launched

The American Society of Gene and Cell Therapy (ASGCT) has unveiled a new online resource designed to keep patients, caregivers, and the public apprised of the latest in gene and cell therapies, including those intended for spinal muscular dystrophy (SMA).

Gene Therapy 101 is the organization’s debut release from its new Patient Education Program, designed by ASGTC committee volunteers in tandem with patient advocacy groups. The program’s aim is to provide information on therapies’ status and potential.

Through February, the organization will also explore five diseases, specifically chosen because of the promising statuses of their gene and cell therapies, according to a press release. The diseases and release dates are: SMA, Feb. 1; X-linked myotubular myopathy, Feb. 12; leukodystrophy, Feb. 15; blood disorders, Feb. 22; and inherited retinal disorders, Feb. 28.

This is particularly relevant for SMA, because Zolgensma — developed by Novartis-owned Avexis — is on its way to potentially becoming the first gene therapy approved for the disease, with a U.S. Food and Drug Administration decision expected in May.

Now available online, Gene Therapy 101 discusses gene therapy basics; different approaches to gene therapy and editing, and cell therapy; and how gene therapies go from concepts to treatments. With the help of videos and downloadable graphics, it also provides a host of resources and frequently asked questions.

The site begins by laying out the basics — what gene therapy is, its history, and how it works, explaining what genes are and how gene therapy can help. It also defines what a rare disease is, lists disorders that have gene therapies, and describes the use of viral vectors.

A section on different approaches discusses how the biomedical research fields of gene therapy, cell therapy, and gene editing have a shared goal of treating diseases by altering the genetic makeup of the human body. Supported by a glossary of terms, it also describes how each approach changes genetic material in slightly different ways.

This section also discusses gene and cell therapy versus traditional medications as well as the challenges and benefits of the therapy, including funding and regulatory issues, optimal means of genetic material delivery, long-term effects and maintenance, and therapeutic agent design.

A third section explaining how therapies progress to treatments also discusses the role of the FDA, and the meaning and impact of federal breakthrough, fast track, regenerative medicine advanced therapy, and priority review designations. In addition, it delves into patient access and finding clinical trials.

The upcoming segment on disease-specific treatments opens with SMA, a disease caused by a change, or mutation, in a person’s DNA. In SMA patients, there’s a mutation in the SMN1 gene, which leads to a lack of SMN protein production, and ultimately to the loss of motor neurons. In humans, a second gene — SMN2 — can produce a small amount of SMN protein, but not enough to maintain muscle function.

Investigators have been working on ways to raise the levels of SMN protein in SMA patients. One approach is gene therapy, which scientists believe may be a way to treat the disease. This involves gene alteration, either by replacing a defective gene or adding a new one.

In addition to Avexis, two other companies are investigating gene therapy approaches for SMA, namely Genzyme (a Sanofi company) and Genethon Inserm.

The ASGTC is the nation’s chief professional membership organization for scientists, physicians, patient advocates, and other professionals with an interest in gene and cell therapy.

Text from:https://smanewstoday.com/2019/01/25/online-patient-education-resource-gene-therapy-101/?utm_content=buffercf097&utm_medium=organic+social&utm_source=facebook.com&utm_campaign=buffer

Very GOOD NEWS about gene therapy Avexis

Patient enrollment is complete for AveXis Phase 1 clinical trial testing its gene therapy candidate AVXS-101 in patients with spinal muscular atrophy (SMA) type 2.

“We are pleased that STRONG is now fully-enrolled and expect to report data from this study by May 2019,” David Lennon, PhD, the company’s president, said in an email reply to SMA News Today.

The trial, named STRONG (NCT03381729), will test the safety and tolerability of single-dose intrathecal injection (into the spinal canal) of 27 patients up to 60 months (5 years) of age who are able to sit but not stand or walk.

Evaluation of the higher dose (1.2 X 10^14 vg) will depend on the safety of the lower dose (6.0 X 10^13 vg), each initially tested in three patients. Patients will be divided into two groups: those younger or older than two years at time of dosing. Effectiveness will be evaluated after 12 months of follow-up.

AVXS-101 is designed to deliver a functional copy of the SMN1 gene to cells that control muscle contractions, called motor neurons. SMN1 is defective in SMA patients, leading to lower levels of a working SMN protein, and subsequently to loss of motor neurons, progressive muscle weakness, and atrophy (shrinkage).

All patients in the STRONG trial have SMN1 gene’s exon 7 deleted in both copies, or alleles. Exons are the bits of DNA with information to generate proteins. These patients also have three copies of the SMN2 gene, which produces an unstable and shorter version of the SMN protein.

AVXS-101 is now under review for approval inthe U.S. and Europe for intravenous (IV) delivery in infants up to 9 months of age who have SMA type 1. A pre-application review period also was started in Japan. Final decisions on whether to approve AVXS-101 are expected in mid-2019.

Recently acquired by Novartis, AveXis has been working to ensure adequate supply of AVXS-101 to patients in case it is approved by the U.S. Food and Drug Administration (FDA), Lennon said.

The recent filings were based mainly on the open-label, dose-escalation Phase 1 START trial (NCT02122952), testing the safety, tolerability and effectiveness of two IV-delivered doses of AVXS-101 in 15 babies with SMA type 1, the most severe and common type of the disease.

“Compared to natural history, AVXS-101 delivered rapid improvement in motor milestone achievements, a dramatic survival benefit, and a durable effect going out four years in SMA type 1 patients,” Lennon said.

Early results of the ongoing Phase 3 STR1VE trial (NCT03306277) in type 1 children younger than 6 months showed improvements in movement ability, as well as no need for respiratory or nutritional support.

Although not part of the current applications for approval, older children with SMA type 2, such as those in STRONG, as well as those with SMA type 3, may be the subject of future filings. “Based on clinical results to date for AVXS-101 in SMA type 1, we expect AVXS-101 delivered via IT [intrathecal] administration to also show a positive benefit in [other] SMA subtypes,” Lennon said.

Besides providing information on the potential benefits of AVXS-101 in SMA type 2, STRONG also will help define the next steps of AveXis’ program. “Because it is our first study of the IT formulation of AVXS-101, data from STRONG will also help determine the final design for our planned study in children up to 18 years of age with SMA types 1, 2 and 3,” Lennon said.

This trial, called REACH, is set to begin in 2019 and will include patients ineligible for the company’s other studies.

Overall, this illustrates the company’s aim to expand the indications treated by AVXS-101. In a February interview with SMA News Today, Suku Nagendran, then AveXis chief medical officer, mentioned how Spinraza (nusinersen, by Biogen) progressed over time as a suggestion of what may lie ahead for AVXS-101.

AveXis provides community update on plans for AVXS-101 in Europe

AveXis has provided SMA Europe with a community update on plans for AVXS-101 in Europe. AVXS-101 is a gene therapy product for SMA.

STR1VE EU

OVERVIEW: STR1VE EU is expected to start enrolling patients in the first half of 2018 in patients with SMA Type 1, studied at multiple centres across the European Union.

ADMINISTRATION: In STR1VE EU, AVXS-101 is administered through a one-time IV infusion.

WHO: STR1VE EU will enroll approximately 30 patients with SMA Type 1 who are less than six months of age at the time of gene therapy.

SPRINT

OVERVIEW: SPRINT is expected to start enrolling patients in the first half of 2018 in presymptomatic patients with SMA Types 1, 2 and 3.

ADMINISTRATION: In SPRINT, AVXS-101 is administered through a one-time IV infusion.

WHO: SPRINT is expected to enroll approximately 44 patients with two, three and four copies of SMN2 who are less than six weeks of age and pre-symptomatic at the time of gene therapy.

REACH

OVERVIEW: REACH is expected to start enrolling patients late in 2018 or early in 2019 in
patients with SMA Types 1, 2 and 3.

ADMINISTRATION: In REACH, AVXS-101 is administered through a one-time IT injection. Data from STRONG (the first study of AVXS-101 delivered through IT injection) will help determine the final study design.

WHO: REACH is expected to enroll approximately 50 patients with SMA Types 1, 2 and 3 who are between approximately six months and 18 years of age.


Text from: http://www.sma-europe.eu/news/avexis-provides-community-update-on-plans-for-avxs-101-in-europe/

AveXis Plans a May Start for Phase 3 European Trial of Its SMA Type 1 Gene Therapy

AveXis’ expects to start a Phase 3 clinical trial of its spinal muscular atrophy (SMA) gene therapy AVXS-101 in Europe in May.

The STR1VE-EU trial (NCT03461289) is expected to include up to 30 children under 6 months of age with type 1 SMA, the disease‘s most severe and common form. All will receive a single dose of intravenous AVXS-101.

The therapy’s safety and effectiveness will be assessed regularly until the babies reach 18 months. At that point, their parents can allow those who are eligible to take part in a long-term follow-up study.

Researchers will be looking at whether the infants can sit without support and also the number who survive until 14 months of age.

The trial will be conducted in Belgium, France, Germany, Italy, the Netherlands, Spain, Sweden, and the U.K. It is expected to be completed in November 2020.

AVXS-101 contains a normal version of the SMN gene that is defective in SMA. Movement nerve cells need a normal version to survive and thrive.

AveXis delivers the gene with a non-infectious virus. The company designed it to be a one-time treatment to prevent muscle degeneration over a lifetime, it said in a recent interview with SMA News Today.

Babies who take part in the STR1VE-EU trial must have mutations of both SMN1 alleles and one or two copies of SMN2. Alleles are gene variations. In most cases, the more copies a patient has of SMN2, the less severe the disease will be.

AveXis has already conducted a Phase 1 trial (NCT02122952) of AVXS-101 in 15 type 1 SMA infants, who received the therapy before they reached six months of age.

The key finding was that all of the children survived for 20 months. This was a huge improvement over what normally happens — 92 percent of children dying by that age.

Another stunning result was that 11 of the 12 children who received the high dose of the therapy were able to sit unassisted, eat food through their mouth, and speak. Nine were able to roll over, and two could walk without help.

AveXis continues to recruit participants for its ongoing STR1VE Phase 3 trial (NCT03306277) in the United States. The trial is also looking at AVXS-101’s safety and effectiveness in children with type 1 SMA who are less than 6 months old. Results similar to those seen in the completed Phase 1 study were observed in the first three children dosed, AveXis said.

Meanwhile, the company continues to recruit patients for its ongoing STRONG Phase 1 trial (NCT03381729) in children up to 60 months of age with type 2 SMA. Unlike the studies in type 1 SMA, which use intravenous therapy administration, patients in the STRONG trials will receive AVXS-101 in the spinal canal, which enables a more targeted treatment.

AveXis also plans the SPRINT trial program for infants under 6 weeks of age with no symptoms but who are likely to develop SMA types 1, 2, or 3, and the REACH program for types 1-3 SMA patients ages 6 months to 18 years who are ineligible for the other studies.

SPRINT and REACH will be worldwide trials. SPRINT is expected to start by mid-2018 and REACH by late 2018 or early 2019.

AveXis and France-based Genethon, which developed AVXS-101, recently announced an agreement granting AveXis the rights to patents in the U.S., Europe and Japan that cover Genethon’s AAV9 SMN gene therapy technology and delivery system. They cover delivery by IV and the spinal canal.

Text from:https://smanewstoday.com/2018/03/23/avexis-sma-gene-therapy-european-phase-3-trial-to-start-in-may/?utm_content=bufferf6d7e&utm_medium=organic+social&utm_source=facebook.com&utm_campaign=buffer

My Rare Disease Day

If you do not like something in your life, just turn the page of your life and start writing again ...

I did so a few years ago. I was destined to be born rare, because I have rare genetic disease Spinal Muscular Atrophy. This is a very rare serious and dangerous disease of muscles and spinal cord, every 10,000 people are born with this disease. And it is incurable yet in any country in the world. In my life there were a lot of hard moments, but there was also a lot of good. But despite this, I've been waiting for a miracle all my life, because I believed that it was possible.

One day in 2013, I read article that the Gene Therapy drug was invented in the USA as a hope for future treatment of SMA. From that moment have passed 5 years and in my life much has changed. I regularly followed of the news of medecine, in which says that in the coming years gene therapy may be available in many countries. And I'm very happy about that. Because during these many years of waiting, new discoveries in medecine are constantly being created and new drugs and ways of treating SMA are being created.

In my life too have been changes. Now every year I go to the Italian clinic Nigrisoli in Bologna for treatment, and I get treatment there from the best specialist of SMA, Dr. Villanova. And I think that this is already a miracle for me.

Text from: https://www.facebook.com/groups/smacuremonika/

SMA Expert Arthur Burghes, Speaking in Poland

Underscoring the enormous progress researchers have made understanding spinal muscular atrophy, Dr. Arthur Burghes called for newborn screening for the incurable degenerative disease and the urgent approval of new therapies for it.

Burghes’ remarks came in a keynote lecture at today’s start of the International Scientific Congress on Spinal Muscular Atrophy in Kraków, Poland. The Jan. 25-27 event is the first in Europe dedicated specifically to the disorder, which occurs in roughly one in every 10,000 births.

Burghes, a professor of biological chemistry and pharmacology at Ohio State University College of Medicine, spoke on the subject “Where Have We Come, Where Do We Go?” The SMA expert, who has a PhD from the University of London and did post-doctoral work at the University of Toronto, has spent 30 years studying the disorder.

“During the time I’ve been researching SMA, we’ve gone from not knowing the gene [underlying the condition], to identifying the gene, to having mice models of the disease, to having large animal models, to actually having therapies,” Burghes told SMA News Today in phone interview Jan. 18 from his lab in Columbus, Ohio. “When those therapeutics are given early in the disease course or even before symptoms occur, they have a major effect on the progression of the disease.”


EU Approval of Spinraza a Turning Point

The conference that Burghes and 400 other SMA experts are attending comes six months after the European Union approved Biogen’s Spinraza (nusinersen) for SMA types 1, 2 and 3.

Type 1, the most severe form of the disease, is usually diagnosed at birth or within the first six months of life. It is caused by mutations of the SMN1 gene that lead to a shortage of the survival motor neuron, or SMN, protein. Spinraza works by altering SMN2, a gene nearly identical to SMN1 that in healthy people generates only a small amount of SMN. The drug’s aim is to cause SMN2 to produce enough functional SMN protein to increase the survival of motor neurons, nerve cells that control movement.

“What pathway is critical for the destruction of motor neurons, or is it a combination of pathways with SMN functioning? What do those pathways each contribute?” Burghes asked. “We don’t really know the answers to these questions, but what’s critical in answering them is to have suppressors that suppress each of those specific pathways and have them tested in mice, so we can learn how the actual biochemistry of the disease works.”

He added that “there are definitely modifiers of the SMA phenotype. Can these modifiers be identified and used in combination with therapies already out there? We don’t know.”

More Approved Therapies Bring Prices Down

Spinraza, which is delivered by injection, has a list price of $125,000 per dose, so the first year’s six injections cost $750,000. This makes it one of the world’s most expensive medications.

Last August, Switzerland’s Roche began enrolling infants with SMA type 1 in a Phase 2 study of RO7034067, a therapy that targets SMN2. The move came after positive early results in a similar study of the compound in older children with type 2 and 3 SMA.

“Spinraza, gene therapy and the Roche compound all induce [trigger the production of] SMN. We need all three of these therapies approved,” Burghes said. “Why? Because it allows competition in the marketplace. If these therapies have to compete against each other, the price will be immediately reduced. So one of the first things we need to do is push forward these clinical studies.”

He explained that “we’ve developed treatments that work very well when given early. They work less well when given in symptomatic cases. That means they don’t have as dramatic an effect, and we would all like the most dramatic effect. So which therapies can you put together to get a more dramatic effect, and how should those go together?”

Full text: https://smanewstoday.com/2018/01/25/sma-expert-arthur-burghes-in-a-speech-in-poland-urges-universal-newborn-screening?utm_content=buffere6ae7&utm_medium=organic+social&utm_source=facebook.com&utm_campaign=buffer

AveXis Announces Alignment with FDA on Next Steps Toward a BLA Submission for AVXS-101 in SMA Type 1

CHICAGO, Jan. 04, 2018 (GLOBE NEWSWIRE) -- AveXis, Inc. (NASDAQ:AVXS), a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today provided an update following the receipt of minutes from the end-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA) conducted on December 5, 2017, regarding the company’s primary gene therapy candidate, AVXS-101, for the treatment of spinal muscular atrophy (SMA) Type 1.

The goal of the end-of-Phase 1 meeting was to review the non-clinical, clinical and Chemistry, Manufacturing and Controls (CMC) data that has been generated by AveXis to date, and to align with the FDA on next steps leading to a Biologics License Application (BLA) submission. The FDA provided detailed information requests in each of the areas discussed, which the company plans to address by submitting the requested information to the investigational new drug (IND) application on an on-going basis. AveXis has been working on many of these areas of focus in anticipation of the requests at some point during the review process. AveXis also plans to provide available data from its on-going pivotal trial of AVXS-101 in SMA Type 1 (STR1VE) prior to the pre-BLA meeting.

“We are very pleased that the constructive and collaborative discussion during the end-of-Phase 1 meeting resulted in the identification of the specific next steps we must take on our path to a BLA submission for AVXS-101 in SMA Type 1,” said Sean Nolan, President and Chief Executive Officer of AveXis. “We greatly appreciate the level of clarity we received from the FDA and will provide our responses on an on-going basis through a series of submissions to the IND, with the expectation that we will request a pre-BLA meeting in the second quarter of 2018.”

The general purpose of the pre-BLA meeting is to outline what information is to be submitted in the BLA and how that information will be submitted. AveXis intends to make the requested data submissions to the IND in advance of the pre-BLA meeting, which may allow the meeting itself to focus on how the BLA and supportive information will be submitted.

Today’s Conference Call Information

AveXis will host a conference call and webcast at 4:30 pm EST today, January 4, 2018. Analysts and investors can participate in the conference call by dialing (844) 889-6863 for domestic callers and (661) 378-9762 for international callers, using the conference ID 8188476. The webcast can be accessed live on the Events and Presentations page in the Investors and Media section of the AveXis website, www.AveXis.com. The webcast will be archived on the company’s website for 90 days and will be available for telephonic replay for 14 days following the call by dialing (855) 859-2056 (Domestic) or (404) 537-3406 (International), conference ID 8188476. Full text:https://globenewswire.com/news-release/2018/01/04/1283628/0/en/AveXis-Announces-Alignment-with-FDA-on-Next-Steps-Toward-a-BLA-Submission-for-AVXS-101-in-SMA-Type-1.html

Gene Therapy Avexis has started 1 Trial in SMA Type 2!

AveXis, Inc., a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today announced the U.S. Food and Drug Administration (FDA) has notified the company that, based on review of data submitted, the company may initiate its planned Phase 1 clinical trial of AVXS-101 for patients with spinal muscular atrophy (SMA) Type 2 via the intrathecal (IT) route of administration, using material produced by the company’s Good Manufacturing Practice (GMP) commercial manufacturing process at the AveXis manufacturing facility. The company plans to initiate this trial immediately.

“We are quite pleased to initiate our first trial of AVXS-101 in patients with SMA Type 2,” said Sean Nolan, President and Chief Executive Officer of AveXis. “Our goal has been to expand the study of gene therapy beyond Type 1 infants to address the urgent medical needs of children with SMA Type 2, and we look forward to understanding the potential clinical impact of AVXS-101 in these patients who, left untreated, will never walk on their own and most will never stand without assistance.”
U.S. Phase 1 Trial in SMA Type 2 (STRONG)

The open-label, dose-comparison, multi-center Phase 1 trial – known as STRONG – is designed to evaluate the safety, optimal dosing, and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The trial will enroll 27 infants and children with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2 genetic modifier, who are able to sit but have no historical or current ability to stand or walk.

Two dosage strengths will be evaluated and patients will be stratified into two age groups: patients less than 24 months, and patients at least 24 months but less than 60 months. There will be at least a four-week interval between the dosing of the first three patients for each dose being studied and, based on the available safety data, a decision will be made whether to proceed.

The trial is projected to be conducted at 11 sites in the United States, including: Ann and Robert H. Lurie Children's Hospital of Chicago, Boston Children's Hospital, Children's Hospital of Philadelphia, David Geffen School of Medicine at UCLA, Johns Hopkins Pediatric Neurology, Nationwide Children's Hospital, Stanford University Medical Center, University of Central Florida College of Medicine, University of Texas Southwestern Medical Center, University of Utah and Washington University School of Medicine.

“This Phase 1 trial in children with SMA Type 2 will allow us to evaluate safety, optimal dosing and proof-of-concept for efficacy of AVXS-101 compared to the well-characterized natural history using the one-time intrathecal route of administration,” said Dr. Sukumar Nagendran, Chief Medical Officer of AveXis. “Because AVXS-101 targets the root cause of SMA, we are optimistic that we will observe a similar preclinical to clinical translation in this Type 2 trial as was seen in the SMA Type 1 study using intravenous administration.” Full text:http://www.curesma.org/news/avxs-101-strong-trial.html

News about GENE THERAPY

WASHINGTON — A first attempt at gene therapy for a disease that leaves babies unable to move, swallow and, eventually, breathe has extended the tots’ lives, and some began to roll over, sit and stand on their own, researchers reported Wednesday.
Only 15 babies with spinal muscular atrophy received the experimental gene therapy, but researchers in Ohio credited the preliminary and promising results to replacing the infants’ defective gene early — in the first few months of life, before the neuromuscular disease destroyed too many key nerve cells.
“They all should have died by now,” said Dr. Jerry Mendell of Nationwide Children’s Hospital, who led the work published by The New England Journal of Medicine. Yet, “those babies are still improving.”
Mendell cautioned that much more study is needed to prove the gene therapy works and is safe. Nor is it clear whether the replacement gene’s effects would wane over time.

Spinal muscular atrophy occurs in about 1 in 10,000 births, and those with the most severe form, called SMA Type 1, rarely reach their second birthday. They can be born looking healthy but rapidly decline. One study found just 8 percent of the most severely affected survived to age 20 months without needing permanent mechanical ventilation to breathe.

There is no cure. The first treatment wasn’t approved until last December — a drug named Spinraza that requires spinal injections every few months.
The experimental gene therapy approach aims for a one-time fix.

WHAT GOES WRONG

Spinal muscular atrophy is caused when a mutated gene can’t produce a protein crucial for survival of motor neurons, nerve cells in the spinal cord that control muscles.
Some children carry extra copies of a backup gene that produces small amounts of the vital protein, and thus have much milder forms of the disease.

GENE REPLACEMENT

Scientists loaded a healthy version of the gene into a virus modified so it couldn’t cause illness. Then 15 babies got a one-time intravenous injection. The virus carried the healthy gene into motor neurons, where it got to work producing the protein those nerve cells require to live.

Three babies received a low dose of the gene therapy, as a first-step safety precaution. The remaining 12 got a high dose.

RESULTS

All of the children are alive, Mendell said, about two years and counting after treatment. All beat the odds of needing permanent machine help to breathe by age 20 months.

But only the high-dose recipients saw better motor control, reaching some developmental milestones usually unthinkable for these patients. Eleven could sit unassisted at least briefly; nine could roll over. Eleven are speaking and able to swallow. Two were able to crawl, stand and then walk, Mendell’s team reported.

Full text:https://www.washingtonpost.com/national/health-science/baby-gene-therapy-study-offers-hope-for-fatal-muscle-disease/2017/11/01/cdd22306-bf42-11e7-9294-705f80164f6e_story.html?utm_term=.6bd2619e4116

AveXis Announces Plan to Initiate Pivotal Trial of AVXS-101 in SMA Type 1

AveXis, Inc., a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today announced the U.S. Food and Drug Administration (FDA) has notified the company that based on review of data submitted, including the potency assay, it may initiate its planned pivotal trial of AVXS-101 for patients with spinal muscular atrophy (SMA) Type 1 using the intravenous (IV) formulation produced by the company’s Good Manufacturing Practice (GMP) commercial manufacturing process. The company plans to initiate this trial immediately.
"We are pleased to reach this outcome following a thorough review by the FDA of the voluminous information we supplied to address the commitments made during the Chemistry, Manufacturing, and Controls Type B meeting in May, and are eager to initiate our pivotal trial of AVXS-101 in SMA Type 1 in the U.S. using product from our GMP process," said Sean Nolan, President and Chief Executive Officer of AveXis. "Moving AVXS-101 back into the clinic, as planned, with product from our GMP process is a significant milestone, not only for AveXis but also for the patients we hope to serve."

The AveXis facility is the production site to supply the pivotal and future trials and, should AVXS-101 be approved for marketing, to meet projected commercial demand.

With the pivotal trial now starting, AveXis and the FDA are continuing discussions on key topics, including dosing, for intrathecal administration of AVXS-101 for the planned clinical trial in patients with SMA Type 2. An update on this program will be provided in the fourth quarter of 2017.

U.S. Pivotal Trial in SMA Type 1 (STR1VE)

The open-label, single-arm, single-dose, multi-center trial – known as STR1VE – is designed to evaluate the efficacy and safety of a one-time IV infusion of AVXS-101 of 1.1 x 1014 vg/kg, which is equivalent to the proposed therapeutic dose received by the second dosing cohort in the Phase 1 trial, in patients with SMA Type 1. Based on the data derived from the company’s new analytical methods that were submitted and reviewed by FDA, it has been determined through direct test with the improved PCR method that the dose used in AveXis’ Phase 1 trial of AVXS-101 in SMA Type 1 was 1.1 x 1014 vg/kg. Additionally, extensive testing in the SMN delta 7 mouse potency assay has demonstrated the equivalence of dose response between the products produced by the Phase 1 and Phase 3 manufacturing process.

The trial will enroll a minimum of 15 patients with SMA Type 1 who are less than six months of age at the time of gene therapy, and who have one or two copies of the SMN2 backup gene as determined by genetic testing and bi-allelic SMN1 gene deletion or point mutations. There will be at least a four-week dosing interval between dosing of the first three patients to allow review of the safety analysis from six time points (days one, two, seven, 14, 21 and 30), as well as early signals of efficacy, prior to dosing of the next patient.

The intent-to-treat population is defined as patients who are less than six months of age and symptomatic at the time of gene therapy, with two copies of the SMN2 gene as determined by genetic testing, bi-allelic SMN1 gene deletion and no c.859G>C mutation in SMN2.

The co-primary efficacy outcome measures of the trial will include:

The achievement of the developmental milestone of independent sitting for at least 30 seconds at 18 months of age; and,
Event-free survival at 14 months of age, with an event defined as either death or at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively.

Co-secondary outcome measures will include:

The ability to thrive, defined as the ability to: remain independent from feeding support, tolerate thin liquids and maintain weight; and,the ability to remain independent of ventilatory support at 18 months of age.
The trial is projected to be conducted at 16 sites in the United States, including: Ann and Robert H. Lurie Children's Hospital of Chicago, Boston Children's Hospital, Children's Hospital Colorado, Children's Hospital of Philadelphia, Columbia University, David Geffen School of Medicine at UCLA, Duke University, Johns Hopkins Pediatric Neurology, Nationwide Children's Hospital, Oregon Health and Science University, Stanford University Medical Center, University of Central Florida College of Medicine, University of Texas Southwestern Medical Center, University of Utah, University of Wisconsin, and Washington University School of Medicine.

"We are appreciative of the detailed reviews and timely feedback we have received from the FDA," said James L’Italien, PhD, Chief Regulatory and Quality Officer for AveXis. "We look forward to our end-of-Phase 1 meeting, which has been scheduled for late in the fourth quarter, to discuss next steps in the regulatory process for AVXS-101."

Full text:http://www.curesma.org/news/avexis-pivotal-trial.html

My dream about cure

In the last days of August I want to tell you about my dream. But this is not just a dream, it is the dream of my life.

From birth I have a serious rare disease. Spinal Muscular Atrophy, since early childhood I could not walk and move but it did not stop me from my dream. I fantasized that one day in world will development magic medicine would be invented and I will be cured. A lot of time has passed since then and a miracle happened - in the beginning of 2000 was created unique drug - Gene Therapy for SMA in clinic in Colambus, Ohio, USA. In 2014 I learned that was started first phase of clinical trial of this drug for children with type 1 SMA, and now very soon will begin 2 phase of this drug for children with SMA type 2.

I do not know what awaits me in the future, but I know what I want and what I awaite. I want TO BE CURE. And this is my dream.

My SMA story for August

This is my SMA story for August

My name is Monika Lemeshonok, I was born on January 27. 1986 in Belarus, city Mogilev. I was born completely healthy child and like all the children started walking at the age of 1 year, I could stand near the crib and walk when I was hold the hand, I was a very active child. But a few months, my mother began to notice how my legs began to weaken when I rested in a chair. My family showed me to a neurologist in the Minsk hospital. At the age of 1.5 years I was diagnosed with SMA type 2 (Spinal Muscular Atrophy), which was later confirmed by genetic DNA analysis. It is a terrible disease affects nerve cells in the upper part of the spinal cord that results in atrophy of the leg muscles and back and then to the loss of movement completely, the person ceases to walk and move.
But despite my disease and physical difficulties from him since childhood, my mother told me that you need to believe in miracles, live and enjoy life. And I've always believed that in one day will happen miracle and I will cure and be able to walk.
I have always admired the world and from an early age loved to draw. At first I was drawing pencils and pens cartoons heroes and then I liked to draw and paint, I painted all around. I started with the teachers of painting in art school.

From a childhood, I gave my personal exhibitions of paintings in many cities in my country and abroad, and help me in this, my mother. Many professionals and art lovers appreciate the artwork on my art exhibition; my works are in private collections in Europe, Asia and America. On one of my exhibitions have helped to me contact with famous professor and neurologist from Moscow Leonora Grinio, who was engaged in embryonic transplant of fetal tissue for people with neuromuscular diseases. The first time I got to her for treatment in 1999 at age 13, where I was made embryonic transplantation of fetal tissue using an injection under the skin. Treatment by Professor L.Grinio was a real miracle for me - I realized that I have a great chance on the way to a dream to be healthy.

I was treated by L.Grinio embryonic fetal cells from 1999 until 2003. In 2004, my professor Leonora Grinio introduced me to academician of the Russian Federation Gennady Suhih- Director of Institute Biological Medicine. And from 2004 to 2011 at the Moscow Institute of Biological Medicine I conducted transplantation of embryonic stem cells into muscle. After this treatment I got stronger muscles of the thighs, my weight began to increase, I do not get sick colds and viral diseases now never, I have always strong energy.

Thanks to this treatment in 2009 I graduated from the State University in my city, specialty Fine Arts, received Excellent diploma.
Another significant event in my life was to get acquainted with the great sculptor and artist Zurab Tsereteli - the first time in June 2003. Zurab personally invited me to their workshops on Tverskaya, the second time in 2008, I was invited to a master class in painting at the Zurab Tsereteli in Moscow on Prechistenka Street in his personal gallery.

I continue to enjoy life and now I have always a lot of inspiration and every day I paint artworks with new strength and believe in a good future.

In 2011 year I finished treatment of stem cells in Moscow, because my body has become stronger and my professor L.Grinio finished medical activities due to illness. At the time she told me about gene therapy - treatment which in the future will treat people with SMA and maybe even cure them completely. Then I did not know which country to seek this treatment, I had no contacts of doctors and clinics. But in 2014 year I saw an article on the internet about what to Nationwide Children's Hospital in Columbus, Ohio began the first phase of clinical trials of gene therapy for children with SMA type 1, which has so far been successful. I wrote message on the further conduct of gene therapy (Avexis) to Jill Jarecki - research director at Families of Spinal Muscular Atrophy (FSMA) and she said that within in three years is planning to conduct clinical trials of gene therapy for people with type 2 SMA.
In first half 2017 I wrote to neurologist John Kissel in Wexner Medical Center (Columbus, Ohio) about future planning participating in clinical trial of Gene Therapy (Avexis) and about me. He is promised that he would put my name and my contacts in the database to participate in these clinical trials in the future. It is was very happy news for me. I look forward and I hope that in the near future I will be able to be included on the clinical trials of gene therapy, because I believe in a miracle that the dream of my life has finally come true.

From October 2016 I got of medical examination and treatment every years in Italy clinic Nigrisoli (Bologna) at the Doctor M.Villanova.

AveXis Announces Alignment with the FDA on Company's GMP Commercial Manufacturing Process for AVXS-101

AveXis today announced alignment with the U.S. Food and Drug Administration (FDA) on the company’s Good Manufacturing Practice (GMP) commercial manufacturing process for AVXS-101 following the receipt of minutes from the Type B Chemistry Manufacturing and Controls (CMC) meeting.

This alignment includes support for the proposed commercial manufacturing process, the proposed analytical methods and corresponding qualification and validation plans – inclusive of key release assays such as potency, purity and identity – and the proposed comparability protocol, which helps assess how similar the product derived from the GMP process is to the original product used in the Phase 1 trial of AVXS-101 in patients with spinal muscular atrophy (SMA) Type 1.

Overall, the company believes there is alignment with the FDA on its panel of analytical methods and the proposed assay qualification/validation plans. Analytical methods are used to assess how reliably and consistently the key product characteristics can be determined in order to ensure patients receive safe and effective product.

In the meeting minutes, the FDA made a request that the company complete implementation of its potency assay qualification plan, presented in the meeting, prior to initiation of upcoming clinical studies.

The company has already initiated the work necessary to address this request and expects to have the data ready to submit to the FDA in the August timeframe. AveXis plans to initiate a pivotal study trial of AVXS-101 in SMA Type 1 in the U.S. and a Phase 1/2a trial of AVXS-101 in SMA Type 2 in the U.S. later in the third quarter of 2017, pending agreement from the FDA that these data are sufficient.

“The goal of the CMC meeting was to align with FDA on our commercial manufacturing process, analytical methods and comparability protocol, all three of which we believe were achieved in this collaborative and constructive discussion,” said Sean Nolan, President and Chief Executive Officer of AveXis. “The team has already made progress toward addressing the FDA’s request regarding potency assay qualification, and we anticipate only a modest impact to timelines. We are pleased with the outcomes of the meeting and the progress we have made at the AveXis facility, and, most importantly, believe we have a scalable GMP commercial process in place to fulfill future patient demand and a path forward to potentially utilize the Phase 1 data in our regulatory pathway.”

Additionally, FDA is aligned with the company’s proposed comparability protocol to assess the similarity of key characteristics of the Nationwide Children’s Hospital (NCH) product, used in the Phase 1 SMA Type 1 study, with the product derived from the new GMP manufacturing process. Data from this comparability work is ongoing and will include the above-mentioned potency qualification data, which will be incorporated into the data package along with the full Phase 1 clinical data, that will be reviewed and discussed at the upcoming end-of-Phase 1 meeting, likely to be requested later in August. This meeting will help further inform the regulatory pathway options for AVXS-101. The company anticipates providing an update on the outcome of that meeting once the official minutes are available, which is anticipated to be in the fourth quarter of 2017.

The company has previously stated that having its own manufacturing facility is a key strategic capability necessary to be successful in gene therapy. The company today reported that the AveXis manufacturing facility is now fully operational for on-going GMP production.

Product for the planned SMA Type 1 pivotal trials and the Type 2 Phase 1/2a trial using intrathecal delivery has been produced at the AveXis-owned facility, and will be used to initiate the trials, pending FDA review of the potency assay qualification described above and FDA agreement that designated batches of the product are appropriate for a Phase 3 clinical study.

The AveXis facility will be the primary production site to meet projected commercial demand, and the company will use contract manufacturing organizations to supplement production.

Full text: http://www.curesma.org/news/avexis-fda-alignment.html

AveXis to Use Intended Commercial GMP Product in SMA Type 2 Study

Wandering news from AveXis!

News from CHICAGO, Dec. 21, 2016 (GLOBE NEWSWIRE) -- AveXis, Inc. (NASDAQ:AVXS), a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today reported that, based on emerging data from its intended commercial Good Manufacturing Practice (GMP) development work and ongoing discussions with the U.S. Food and Drug Administration (FDA), the company has made the strategic decision to use the intended commercial GMP derived product in all future studies of the company’s proprietary gene therapy candidate, AVXS-101, including the planned spinal muscular atrophy (SMA) Type 2 trial.

The company had originally planned to use existing inventory for its initial trial in SMA Type 2, and to then use its intended commercial GMP derived product in later Type 2 trials. By using the intended commercial GMP derived product for the duration of its study of AVXS-101 in Type 2 patients, the need for a comparability analysis later in program development is eliminated, potentially accelerating the timeframe for gathering clinical data that may be used as part of a data set to support a future SMA Type 2 indication.

“We believe this strategic decision has the potential to streamline the development of the clinical data set for AVXS-101 in SMA Type 2,” said Sean Nolan, President and Chief Executive Officer of AveXis. “We are pleased with the advances we have seen from our process development efforts and believe the optimal approach is to use the scalable process in our clinical evaluation of AVXS-101 in SMA Type 2 from the outset.”

The company now expects to initiate the planned study of AVXS-101 in SMA Type 2 patients in Q2 2017, assuming a positive outcome from its Type B manufacturing meeting with the FDA, currently anticipated to occur in Q1 2017.

This approach is intended to potentially expedite the SMA Type 2 program and does not impact the development program for AVXS-101 in SMA Type 1. AveXis expects to initiate a U.S. pivotal trial of AVXS-101 in patients with SMA Type 1 in the first half of 2017, and plans to use the same intended commercial GMP derived product for that study.

Conference Call Information
AveXis will host a conference call and webcast at 4:30 p.m. EST today, December 21, 2016, to discuss this clinical development update for AVXS-101.

Analysts and investors can participate in the conference call by dialing (844) 889-6863 for domestic callers and (661) 378-9762 for international callers, using the conference ID 43591277. The webcast can be accessed live on the Events and Presentations page in the Investors and Media section of the AveXis website, www.AveXis.com. The webcast will be archived on the company’s website for 30 days, and will be available for telephonic replay for 14 days following the call by dialing (855) 859-2056 (Domestic) or (404) 537-3406 (International), conference ID 43591277.

About SMA
SMA is a severe neuromuscular disease characterized by the loss of motor neurons leading to progressive muscle weakness and paralysis. SMA is caused by a genetic defect in the SMN1 gene that codes SMN, a protein necessary for survival of motor neurons. The incidence of SMA is approximately one in 10,000 live births. SMA is the leading genetic cause of infant mortality.

The most severe form of SMA is Type 1, a lethal genetic disorder characterized by motor neuron loss and associated muscle deterioration, which results in mortality or the need for permanent ventilation support before the age of two for greater than 90 percent of patients. Approximately 30 percent of cases are expected to be SMA Type 2. SMA Type 2 typically presents between six and 18 months of age. Affected patients will never walk without support, and SMA Type 2 results in mortality for more than 30 percent of patients by age 25.

About AVXS-101
AVXS-101 is a proprietary gene therapy candidate of a one-time treatment for SMA Type 1 and is designed to address the monogenic root cause of SMA and prevent further muscle degeneration by addressing the defective and/or loss of the primary SMN1 gene. AVXS-101 also targets motor neurons providing rapid onset of effect, and crosses the blood brain barrier allowing an IV dosing route and effective targeting of both central and systemic features.

About AveXis, Inc.
AveXis is a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases. The company’s initial proprietary gene therapy candidate, AVXS-101, is in an ongoing Phase 1 clinical trial for the treatment of SMA Type 1. For additional information, please visit www.avexis.com.

Forward-Looking Statements
This press release contains "forward-looking statements," within the meaning of the Private Securities Litigation Reform Act of 1995, regarding, among other things, AveXis’ research, development and regulatory plans for AVXS-101, including the potential of AVXS-101 to positively impact quality of life and alter the course of disease in children with SMA Type 1, expectations regarding design and timing of the SMA Type 2 trial of AVXS-101 and the overall clinical development of AVXS-101 and AveXis’ manufacturing processes. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual results to differ materially from those projected in its forward-looking statements. Meaningful factors which could cause actual results to differ include, but are not limited to, the scope, progress, expansion, and costs of developing and commercializing AveXis’ product candidates; regulatory developments in the United States and foreign countries, as well as other factors discussed in the "Risk Factors" included as Exhibit 99.1 to the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on September 7, 2016 and the "Management's Discussion and Analysis of Financial Condition and Results of Operations" section of AveXis’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2016, filed with the SEC on November 10, 2016. In addition to the risks described above and in the Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the SEC, other unknown or unpredictable factors also could affect AveXis’ results. There can be no assurance that the actual results or developments anticipated by AveXis will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, AveXis. Therefore, no assurance can be given that the outcomes stated in such forward-looking statements and estimates will be achieved.

All forward-looking statements contained in this press release are expressly qualified by the cautionary statements contained or referred to herein. AveXis cautions investors not to rely too heavily on the forward-looking statements AveXis makes or that are made on its behalf. These forward-looking statements speak only as of the date of this press release (unless another date is indicated). AveXis undertakes no obligation, and specifically declines any obligation, to publicly update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Text from oficial site AveXis: http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2231235

5 Experimental SMA Therapies You Might Find Interesting

1. AVXS 101

Recently, AveXis’ gene therapy candidate AVXS-101, the only gene therapy for spinal muscular atrophy currently in human testing, has been granted FDA orphan drug status for treatment of all types of SMA. It was also granted FDA breakthrough therapy designation and was fast track designation.


2. CK-2127107 (CK-107)

In collaboration with Astellas, Cytokinetics is developing CK-2127107 (CK-107), a new skeletal muscle troponin activator as a potential treatment for people living with SMA. CK-107 has completed five Phase 1 clinical trials in healthy volunteers, and is currently the subject of two Phase 2 clinical trials.


3. Nusinersen

Biogen and Ionis Pharmaceuticals recently announced that nusinersen, their investigational drug for treating SMA, met the primary end point for the interim analysis of the ENDEAR Phase 3 trial evaluating nusinersen in infantile-onset SMA.


4. RG7800

PTC’s more developed SMA drug candidate, RG7800, is the subject of a Phase 2 trial in adult and pediatric SMA patients, but dosing was suspended and the trial was placed on clinical hold to investigate a non-clinical safety finding observed in a longer-term animal study.


5. Gene Therapy

Learn more about how gene therapy can be used to treat SMA:http://smanewstoday.com/tag/gene-therapy/

http://smanewstoday.com/social-clips/2016/09/06/5-sma-experimental-therapies-you-should-know-about/5/

Good news about AveXis

Good news!

AveXis Reports Data from Ongoing Phase 1 Trial of AVXS-101 in Spinal Muscular Atrophy Type 1

-- Jerry Mendell, MD, Presented Data as of April 1, 2016 at the American Society of Gene & Cell Therapy 19th Annual Meeting --

-- Company to Host Webcast Today at 4:30 p.m. Eastern Daylight Time --

CHICAGO, May 06, 2016 (GLOBE NEWSWIRE) -- AveXis, Inc. (AVXS), a clinical-stage gene therapy company developing novel treatments for patients suffering from rare and life-threatening neurological genetic diseases, today presented an interim analysis of data as of April 1, 2016 from the ongoing Phase 1 trial of AVXS-101 for the treatment of spinal muscular atrophy (SMA) Type 1. Jerry Mendell, MD, director of the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, presented the data at the 19th Annual Meeting of the American Society of Gene & Cell Therapy in Washington, D.C.

Full text:http://finance.yahoo.com/news/avexis-reports-data-ongoing-phase-191000149.html

SMA Clinical Trial Symposium

This is progress in medicine!

"SMA Clinical Trial Symposium" ---> Taping now at the 2016 FightSMA Annual Research Conference. Lots of incredible progress being made in SMA therapeutics and we look forward to sharing the footage with you online shortly.

Special thank you to our incredible panelists:

Chris Lorson, PhD, University of Missouri, FightSMA Science Director

Alex MacKenzie, MD, PhD, Children's Hospital of Eastern Ontario

Brian Kaspar, PhD, AveXis

Douglas Sproule, MD, MSc, AveXis

Frank Bennett, PhD, Ionis

Wilson Farwell, MD, MPH, Biogen

Lawrence Charnas, MD, PhD, Novartis

Friedrich Metzger, PhD, Genentech/Roche

Stacy Rudnicki, MD, Cytokinetics

Kathy Swoboda, MD, Massachusetts General Hospital Center for Human Genetics

https://www.facebook.com/fightsma/?fref=photo

CLINICAL TRIAL FOR PEOPLE WITH SMA - CONTACTS

ISIS

Contact: Isis Pharmaceuticals, Inc. 1-800-679-4747 patients@isisph.com


Locations
United States, California Stanford University Medical Center Recruiting Stanford, California, United States, 94305 Contact: Shirley Paulose, MBBS, MS 650-724-3792 spaulose@stanford.edu Principal Investigator: John Day, MD

United States, Florida Nemours Children's Hospital Recruiting Orlando, Florida, United States, 32827 Contact: Dawn Cook, RN,MSN,CCRC 407-650-7156 dcook@nemours.org Principal Investigator: Richard Finkel, MD

United States, New York Columbia University Medical Center Recruiting New York, New York, United States, 10032 Contact: Rosangel Cruz, MA, BS 212-305-1336 rc2836@columbia.edu Contact: Jonathan Marra, MA 212-305-2461 jdm2132@columbia.edu Principal Investigator: Claudia Chiriboga, MD Canada, Ontario

The Hospital for Sick Children (SickKids) Recruiting Toronto, Ontario, Canada, M5G 1X8 Contact: Lynn MacMillan, RN
416-813-7355 lynn.macmillan@sickkids.ca Principal Investigator: Jiri Vajsar, MD

Other Sites...
United States, Massachusetts Boston Children's Hospital Boston, Massachusetts, United States, 02115

United States, New York Columbia University Medical Center New York, New York, United States, 10032

United States, Texas UT Southwestern Medical Center - Children's Medical Center Dallas Dallas, Texas, United States, 75207

United States, Utah University of Utah School of Medicine Salt Lake City, Utah, United States, 84132



GENE THERAPY


Jerry R. Mendell, MD
Neurology

Neurology
700 Children's Dr
Columbus, OH 43205
(614) 722.2715


Brian K. Kaspar, Ph.D.

The Research Institute at Nationwide Children's Hospital
700 Childrens Drive
Columbus, OH 43205
(614) 722-2700


Information from "SMA Support System" - https://www.facebook.com/groups/SMASupportSystem/files/

https://www.facebook.com/notes/sma-support-system/locate-a-doctor-or-clinical-trial-center/526919677400146