includes support for our proposed GMP commercial manufacturing process, our proposed analytical methods and corresponding qualification and validation plans inclusive of
key release assays such as potency, purity and identity and our
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 SMA
components of our scalable, GMP commercial manufacturing process are as follows:
- we will continue to utilize HEK293 cells and an adherent cell line;
- our commercial-scale GMP process will utilize a novel adherent cell culture approach that can more reliably produce product and has greater
surface area to potentially increase productivity relative to Hyperstacks;
- we have implemented additional upstream and downstream process development improvements to meet global regulatory GMP expectations as well as
to meet projected patient demand, if approved; and
- we intend to utilize our GMP process for all clinical and commercial needs moving forward, including our new programs in Rett syndrome and ALS
response to a request from the FDA, we intend to complete the implementation of our potency assay qualification plan, including three independent runs, prior to initiation of
upcoming clinical trials. This assay utilizes the Delta 7 mouse model, which has been used historically to assess AVXS-101 potency, but now incorporates additional elements to make it acceptable to
global regulatory authorities. We have initiated the work necessary to meet that request and we expect to have the data from these production runs to submit to the FDA in the August 2017 timeframe.
Pending agreement from the FDA that the data from these production runs are sufficient, we intend to initiate our pivotal trial of AVXS-101 in SMA Type 1 in the United States and a
Phase 1/2a clinical trial of AVXS-101 in SMA Type 2 in the United States later in the third quarter of 2017.
we are currently conducting comparability work to assess the similarity of key characteristics of the AVXS-101 product used in our Phase 1 clinical trial in SMA
Type 1, which was manufactured by the Nationwide Children's Hospital, or NCH, to the product derived from our new GMP manufacturing process. Data from this comparability work will be
incorporated into the data package, and will include the above mentioned potency qualification work, along with the full Phase 1 clinical data, that will be reviewed and discussed at our
end-of-Phase 1 meeting with the FDA, which we anticipate requesting later in August 2017. We expect that this meeting will help further inform the regulatory pathway for AVXS-101. We anticipate
providing an update on the outcome of that meeting once the official minutes are available, which we anticipate to be in the fourth quarter of 2017.
License Agreement with REGENXBIO for Rett Syndrome and Genetic ALS
On June 7, 2017, we announced that we had entered into an exclusive, worldwide license agreement with REGENXBIO Inc. for the
development and commercialization of gene therapy using the recombinant adeno-associated virus serotype 9, or NAV AAV9, vector to treat two rare neurological monogenic disorders: Rett syndrome
and a genetic form of amyotrophic lateral sclerosis, or ALS, caused by mutations in the superoxide dismutase 1, or SOD1, gene. Preclinical data
suggesting promising safety and efficacy of gene therapy treatments for these disorders using NAV AAV9, generated by our Chief Scientific Officer, Dr. Brian Kaspar, has been licensed from NCH
by the Company. We expect to move forward with initiating investigational new drug application, or IND, enabling studies in both Rett syndrome and ALS and plan to provide more details on these
programs in the second half of 2017.