AveXis Issues Community Statement on BLA Acceptance

AveXis has provided the following community statement on the BLA submission and acceptance for their investigational therapy, AVXS-101 – now known as ZOLGENSMA®.

Dear SMA Community,

We are providing this update to the SMA community in the U.S. at the request of Cure SMA. Following our recent October update about our Biologics License Application (BLA) submission, AveXis, a Novartis company, is pleased to share that the U.S. Food and Drug Administration (FDA) has now accepted the BLA for our investigational therapy, AVXS-101 – now known as ZOLGENSMA® (onasemnogene abeparvovec-xxxx1) – for use in patients with SMA Type 1. The FDA has granted the application a Priority Review, which means the agency will review the application within six months instead of the typical 10 months. The agency’s decision on whether or not to approve ZOLGENSMA is expected by May 2019.

Data from our pivotal Phase 1 study conducted in SMA Type 1 formed the primary basis for this submission. Based on the data included in the application, our expectation is that the initial label will be for intravenous (IV) use of ZOLGENSMA for infants with SMA Type 1.

The goal of gene therapy is to address the underlying, genetic root cause of diseases with a one-time treatment. The acceptance of our BLA filing is an important step in the process as we get closer to potentially making ZOLGENSMA available to patients with SMA Type 1, and their families. We remain committed to the development of ZOLGENSMA for all forms of SMA and have additional trials underway or planned to investigate use in other subtypes.

We look forward to continuing to keep you updated.

The AveXis Team

Frequently Asked Questions

1. If ZOLGENSMA is approved by the FDA, who will be eligible to receive it?

The pivotal Phase 1 study in SMA Type 1 formed the primary basis for the BLA submission. Given this, our expectation is that the initial label will be for intravenous (IV) use of ZOLGENSMA for infants with SMA Type 1.

2. I read that AveXis is now offering a Managed Access Program (MAP) for U.S. patients – what is it?

  • There are instances where a patient has a serious or life-threatening disease or condition, for which all currently available treatment options have been exhausted and enrollment into a clinical trial is not possible.
  • In these cases, the treating physician can request an investigational AveXis product prior to regulatory approval, provided it is allowed by the applicable local laws. Within AveXis, we refer to such provision of investigational products as “Managed Access Program.”

3. Who is Eligible for AveXis’ MAP for U.S. patients?

The following criteria* must be met by infants with symptomatic SMA to participate in an AveXis MAP:

  • An independent request must be from the treating physician
  • The patient to be treated has a serious or life-threatening disease or condition, and no satisfactory alternative therapy is available, or has exhausted approved treatment options to monitor or treat the disease or condition
  • The patient is ineligible for enrollment into or unable to access ongoing clinical trials
  • Sufficient information exists to believe the potential benefit of treatment outweighs the potential risk in the context of the disease or condition to be treated
  • AveXis has an adequate supply of the investigational product and providing the product will not interfere with ongoing clinical trial(s) or with the overall development program
  • The patient meets any other important medical criteria established by the medical experts working on the product development program:

These other important medical criteria are measured against the inclusion criteria and outcome of our Phase 1 trial for SMA Type 1 patients

*All above criteria are subject to local laws and regulations

4. Do you have a program for older patients with SMA Type 1, or patients with SMA Types 0, 2, 3 and 4?

  • A MAP may only be activated upon successful completion of a Phase 1 trial to determine safety and dosage of the product. In this case, the MAP would be based on the IV formulation of AVXS-101.
  • The AveXis MAP in the U.S. currently only addresses infants with SMA who meet specific considerations.
  • Our goal is to make ZOLGENSMA available to all SMA patients through a rigorous research and clinical development program.
  • Please see the list table of current clinical trials listed at the end of this letter.

5. Are patients outside of the US eligible for the MAP?

6. What is the reason for intrathecal dosing vs. intravenous? Why can’t older patients be dosed with IV?

  • We are exploring two routes of administration in our ongoing clinical trials: intravenous (IV) for infantile onset SMA, and intrathecal (IT) for older children.
  • ZOLGENSMA uses a AAV9 viral capsid shell to deliver a fully functional human SMN gene.
  • IV treatment with ZOLGENSMA is dosed by weight, meaning the heavier the patient, the more vector that is used. To date, the heaviest patient dosed on ZOLGENSMA was 8.4 kg.
  • When using IT in larger patients there is a lower total viral vector load than IV. Therefore, IT delivery allows for a lower vector exposure to older, heavier patients.
  • Further studies are warranted to understand how much viral vector is tolerable to patients.
  • We are currently evaluating the appropriate dose for IT delivery in the STRONG trial.

7. What is the status of the IT Phase 1 STRONG trial in patients with SMA Type 2? Why is a third dose being considered?

  • STRONG is an open-label, dose-ranging, multi-center Phase 1 trial 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 (patients 6 to- The STRONG trial is currently fully-enrolled at the low- and mid-dose cohorts.
  • An important objective of the STRONG study is to determine the optimal IT dose. Commonly, in early clinical development, escalating doses are studied in order to maximize efficacy while monitoring safety of patients closely.
  • The rationale for considering a higher dose is to explore whether it will provide the opportunity for additional efficacy, leading to potentially optimized functional outcomes, while continuing to be safe for patients.

8. What about the older kids with SMA?

  • The ideal moment to initiate therapy is before the development of significant, irreversible injury. For this reason, it is understandable that much of the attention in early clinical development programs has focused on younger children.
  • We recognize the need to attend to the whole SMA population, particularly older children and adults with all forms of the disease and are evaluating the steps necessary to study the older patients.
  • AveXis plans to study ZOLGENSMA in older children, and the REACH trial will include patients between approximately six months and 18 years of age.

9. What about adults with SMA?

  • Our goal is to make ZOLGENSMA available to all SMA patients through a rigorous research and clinical development program.
  • The data from the STRONG trial, which will help inform the design of the REACH trial, will better inform the potential impact of ZOLGENSMA in a broader group of patients with SMA.
  • We understand the urgency for all patients with SMA and continue to evaluate the potential of expanding our clinical development program into adults. Data from these planned and ongoing studies will help us understand how to best design future trials.

10. How much will ZOLGENSMA cost?

  • The price of ZOLGENSMA has not yet been established.
  • At the Novartis Research and Development (R&D) day on November 5th, we shared health economic analysis that showed the ten-year costs of treating ultra-rare diseases with chronic therapies, including SMA, range from two to five million dollars. There was also discussion around an analysis that shows our investigational gene therapy, ZOLGENSMA, would be cost effective up to four to five million dollars in SMA Type 1.
  • These comparisons were provided to put into context the current costs associated with treating these types of conditions and the potential value that gene therapy could bring.
  • As was stated at the Novartis R&D day, we want to reiterate that this cost effectiveness analysis should not be interpreted as being the price of ZOLGENSMA.
  • Our objective is to ensure patients get access to this therapy, so we can make a meaningful difference in their lives.

11. How will you ensure patients have access to ZOLGENSMA once it is approved?

  • The goal of gene therapy is to address the underlying, genetic root cause of diseases with a one-time treatment. Introducing such a one-time therapy will require rethinking how our healthcare system manages diagnosis, treatment, care and associated costs for patients with genetic diseases
  • Our objective is to ensure patients get access to this therapy, so we can make a meaningful difference in their lives. Our gene therapy will be priced cost-effectively for the healthcare system. We are working closely with payers to ensure we establish appropriate prices reflecting the value of gene therapy and explore creative options for payers, including installment payment options as well as outcomes-based arrangements.

Overview of AVXS-101 Clinical Development Program (as of December 2018)

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