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

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’ AVXS-101 Shows Promise in Treating Infants with SMA Type 1

The Phase 1 study (NCT02122952) investigated the effects of AVXS-101 treatment by intravenous injection in 15 infants with SMA type 1 who were six months old or younger. Two doses were compared, the lower dose for Cohort 1 with three patients, and the higher dose for Cohort 2 with 12 patients.

The treatment’s short-term safety was evaluated over a two-year period, but a follow-up safety analysis will be carried out when the last patient reaches 2 years of age post-treatment. Patients will then be monitored annually as per standard of care for up to 15 years.

The endpoints measured were the time from birth to an “event” (death or at least 16 hours of daily ventilation support for 14 consecutive days in the absence of acute reversible illness or perioperatively) and the ability to sit independently, confirmed by video. Researchers also assessed patients with a standard motor milestone development survey and the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).

An interim data analysis, released lasted year, revealed a favorable safety profile with no new treatment-related safety or tolerability concerns identified. Motor skill improvements were also observed, especially in children treated with the higher dose.

As of Jan. 20, 2017, AVXS-101 maintains its safety profile and was well-tolerated by the patients. Indeed, 12 out of 12 patients (100%) who received the highest one-time therapeutic dose of AVXS-101 (Cohort 2) reached 13.6 months of age without events reported. Of note, the expected event-free survival rate for this disease is 25%.

Results also showed that 11 patients (92%) in this cohort achieved head control, nine patients (75%) were able to roll a minimum of 180 degrees from back to both left and right, and 11 patients (92%) could sit without help.

After the treatment, AveXis used three different measures to evaluate unassisted sitting with increasing amounts of time. Results showed that nine of 12 patients (75%) sat unassisted for five seconds, seven (58%) sat for at least 10 seconds, and five patients (42%) sat for 30 seconds or more. Also, two patients could walk independently, besides having achieved other milestones, including standing with support, standing alone, and walking with support.

In addition, as of Jan. 20, 2017, nine of nine patients (three in the low-dose cohort and six in Cohort 2) — reached 20 months without reported events. Here, the expected event-free rate is 8%.

“The completion of our Phase 1 clinical study of AVXS-101, the first ever gene therapy studied for the treatment of SMA type 1, is an exciting and eagerly awaited milestone, and we are quite pleased with these data,” Sean Nolan, AveXis’ president and CEO, said in a news release.

“The past few months have been productive for AveXis, and we look forward to continuing the momentum with several upcoming corporate catalysts … as well as ongoing collaborative discussions with regulatory authorities in the United States and Europe to explore the most expeditious pathways for marketing approval of AVXS-101,” Noland added.

Text from: https://smanewstoday.com/2017/04/06/avexis-avxs-101-shows-promise-treatment-infants-sma-type-1/

Again news from Avexis

CHICAGO, Feb. 06, 2017 (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 announced that the planned pivotal study of AVXS-101 in spinal muscular atrophy (SMA) Type 1 in the European Union (EU) will reflect a single-arm design, using natural history of the disease as a comparator, and will enroll approximately 30 patients. This update is based on the receipt of the Scientific Advice response from the Scientific Advice Working Party within the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

In addition to evaluating safety the planned pivotal trial is expected to evaluate achievement of motor milestones, specifically patients’ ability to sit unassisted, as well as an efficacy measure defined by the time from birth to an “event,” defined as death or requiring at least 16 hours per day of ventilation support for breathing for greater than two weeks in the absence of an acute reversible illness, or perioperatively.

“The scientific advice process has been quite productive, with the EMA providing constructive guidance on a pivotal study design most appropriate for EU product registration,” said James L’Italien, Ph.D., Senior Vice President, Chief Regulatory and Quality Officer of AveXis. “We will utilize the enhanced communication pathways afforded to us via the PRIority MEdicines program and work in collaboration with the EMA to generate the high-quality data needed to support the most rapid submission that meets the requirements for marketing authorization in the EU.”

The CHMP additionally recommended AveXis discuss the potential for Conditional Marketing Authorization in a future meeting with EMA.

More specific clinical trial details will be made available at the time the study is initiated, which is expected in the second half of 2017.

The company expects to initiate a separate pivotal clinical trial of AVXS-101 in SMA Type 1 in the United States in the first half of 2017.

Text from:http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2243247

AveXis Gene Therapy AVXS-101 Granted Access into EMA PRIME Program for Spinal Muscular Atrophy Type 1!!

Great news from Avexis!

CHICAGO, Jan. 31, 2017 (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 announced that the European Medicines Agency (EMA) has granted access into its PRIority MEdicines (PRIME) program for the company’s proprietary gene therapy, AVXS-101, for the treatment of spinal muscular atrophy (SMA) Type 1. The PRIME application was based on data from both preclinical evaluations and the ongoing Phase 1 clinical trial of AVXS-101 as of September 15, 2016.

PRIME is intended to enhance support for the development of medicines – specifically those that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options – through early and proactive support by EMA to optimize the generation of robust data and development plans, and potentially expedite the assessment of the Marketing Authorization Application (MAA) so these medicines may reach patients sooner.

“The acceptance of AVXS-101 into the PRIME program reflects the urgent need for innovative treatment options for the patients diagnosed with SMA in the European Union,” said James L’Italien, Ph.D., Senior Vice President, Chief Regulatory and Quality Officer of AveXis. “We are eager for this enhanced collaboration with the EMA to ensure we are taking the most appropriate and expeditious path toward the development of a robust Marketing Authorization Application submission, and to potentially streamlining the time needed to bring AVXS-101 to patients in the EU suffering from this devastating disease.”

In notifying the company of the acceptance, EMA noted: “The preliminary clinical observations following AVXS-101 administration include positive impact on survival, pulmonary function, nutritional support, preservation of motor function and the attainment of development milestones, all of which are unexpected within the framework of the natural history and disease progression for SMA Type 1. These clinically meaningful responses in the patients treated with AVXS-101 are sufficient preliminary clinical evidence of treatment effect that has the potential to address an unmet need in this devastating pediatric disease.”

In July 2016, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation, a comparable program to PRIME used by the FDA, for AVXS-101 for the treatment of patients with SMA Type 1.

AveXis intends to initiate a pivotal trial of AVXS-101 in patients with SMA Type 1 in the European Union before the end of 2017.

About PRIME

The EMA launched the PRIME initiative in March 2016 to foster research and development of medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. PRIME aims to strengthen clinical trial designs to facilitate the generation of high quality data for the evaluation of an application for marketing authorization. To be accepted for PRIME, a medicine has to show its potential to benefit patients with unmet medical needs based on preclinical and/or early clinical data. These medicines are considered priority medicines within the European Union.

After an investigational candidate has been selected for PRIME, developers are assigned a rapporteur from the Committee for Medicinal Products for Human Use (CHMP) to provide continuous support and help to build knowledge ahead of a Marketing Authorization Application (MAA). A multidisciplinary group of experts will provide broader guidance on the overall development plan and regulatory strategy of the product. Companies are also eligible for accelerated assessment at the time of their regulatory application.

For more information, please visit the research and development section of www.ema.europa.eu

Text from: http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2240880

FDA give feedback on SMA gene therapy trial

US gene therapy company, Avexis, recently announced that it has met with FDA officials and received constructive feedback about its AVXS-101 development programme for SMA type 1. The company plans to initiate a single-arm phase 1 study in the first half of 2017. There will not be a placebo group in this study so the resulting data will be compared against natural history data.

The FDA requested to be briefed on the results once the study is completed: “We strongly recommend that at the completion of the study, you request an end-of-Phase 1 meeting to evaluate the adequacy of data to support future product development, including a discussion of whether the data from the Phase 1 study might provide the substantial evidence necessary to support a marketing application.”

For more information, read Avexis http://investors.avexis.com/phoenix.zhtml?c=254285&p=irol-newsArticle&ID=2218102

http://www.musculardystrophyuk.org/news/breaking-research-news/

Help to Artyom!

SMA Awareness Month on the ends. And I want to once again talk about little boy Artyom, he has SMA type 1, and he with his parents lives near me. He always needs a specially adapted for his life. He as all children with SMA waits and hopes that in soon time will created drug from SMA and it will receive all the children and people with SMA. We all believe in it.

Expanded Access Program for Nusinersen in Participants for SMA 1 type

In soon time we wait for a miracle drug for SMA

Biogen is working to open a global expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1) in the coming months. The EAP can be initiated at existing nusinersen clinical trial sites in countries where EAPs are permitted according to local laws and regulations, can be operationalized, and where there is a path that can support long-term availability of nusinersen. Once the EAP is operational and required local approvals are in place, individual participating sites may start enrollment after they have transitioned ENDEAR study participants to the open-label extension study.

More information on the EAP can be found on the clinicaltrials.gov website under the NCT identifier NCT02865109 https://clinicaltrials.gov/ct2/show/NCT02865109

Full text: http://www.curesma.org/news/important-milestone-reached.html

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

Help to Artyom!

Hi, Everyone!

Today I want to introduce you with Artyom, who has Spinal Muscular Atrophy type 1. He needs your help. Artyom could not move, he can not breathe and can not eat himself.

This terrible disease affects the upper sections of the spinal cord that weakens the muscles of the entire body, and he can not walk, move, and with SMA type 1, a person does not breathe by himself.


Help to him NOW! https://vk.com/club92186792