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AVEXIS, INC. filed this Form 10-K on 02/28/2018
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We have generated AVXS-201 by leveraging our manufacturing platform and are utilizing a process very similar to AVXS-101.  We have successfully completed engineering lots, along with a cGMP manufacturing run intended for clinical use, and we have also developed key analytical assays suited for AVXS-201. 

Genetic ALS

ALS is a progressive, fatal, neurodegenerative disease that affects motor neurons in the brain and the spinal cord. Symptoms of ALS include progressive weakness and atrophy of muscles controlling voluntary movement, swallowing, speech and breathing, and most commonly develops between 40 and 70 years of age. Genetic forms of ALS comprise five to ten percent of all ALS cases, and approximately twenty percent of genetic ALS cases are caused by mutations in the SOD1 gene, which are toxic to motor neurons.  In 2013, there were 15,908 patients with “definite ALS” in the United States, a prevalence rate of approximately five of every 100,000 persons. Approximately 800 to 1,600 of these cases were due to genetic causes of ALS.  

Our Product Candidate: AVXS-301 for the Treatment of Genetic ALS

We are conducting preclinical studies of AVXS-301, our proprietary gene therapy product candidate for the treatment of genetic ALS.  In previous studies in the laboratory of Dr. Kaspar at NCH, we utilized AAV9 carrying a green fluorescent protein reporter to deliver a short hairpin RNA, or shRNA, targeting the mutant human SOD1 transgene. We observed improved disease outcome in two different mouse models of ALS following a one-time administration, even when delivered at the time of disease onset. We also observed that this treatment was safe and well-tolerated in wild-type mice.  Based on these preclinical studies, we developed AVXS-301, which, like AVXS-101, is composed of an AAV9 capsid shell.  In preclinical studies of an AAV9 vector with a SOD1 shRNA expression cassette and a non-coding stuffer sequence instead of GFP, we observed efficient SOD1 downregulation in vitro, and in vivo efficacy in delaying disease onset and progression. 

We have studied the administration of AVXS-301 both intravenously and directly into the cerebral spinal fluid, or CSF, in mice that overexpress human mutant SOD1.  We observed that both administrations improved rotarod motor performance and hindlimb grip strength.  In our preclinical mouse studies, we observed that a single administration of AVXS-301 directly into the CSF resulted in a greater than 51% increase in survival in the most severe ALS mouse model.  We also conducted preclinical studies in non-human primates, where we observed that a single lumbar intrathecal infusion of AVXS-301 resulted in approximately 90% SOD1 reduction throughout the monkey spinal cord.  Results from other studies in the field suggest that SOD1 may be involved in more than SOD1-linked disease mutations, which we believe may increase the scope of patients that may be treatable with AVXS-301.

We have developed a manufacturing process for both AVXS-201 and AVXS-301 by leveraging our AVXS-101 manufacturing platform. As such, we are utilizing a manufacturing process very similar to AVXS-101. We have successfully completed engineering lots for both AVXS-201 and AVXS-301. We intend to complete cGMP clinical manufacturing runs for both products in the near future.    


We have established our own commercial scale cGMP‑compliant manufacturing facility to enhance supply chain control, increase supply capacity for clinical trials and ensure commercial demand is met in the event that AVXS‑101 receives marketing approval. We intend to use our cGMP manufacturing process for all clinical and commercial production of AVXS-101. We manufacture AVXS‑101 using adherent human embryonic kidney, or HEK, 293 cells. HEK293 cells have been used successfully to manufacture numerous other gene therapy candidates that have been tested or are currently being tested in other clinical trials to date. We use a novel and scalable adherent cell culture approach for AAV9 vector production that can more reliably produce product and has greater surface area to potentially increase productivity relative to traditional flat stock approaches.

Although we anticipate that our manufacturing facility will be the primary production site to meet projected clinical and commercial demand, we will continue to evaluate, and will pursue as needed, potential third parties and/or additional internal sources of redundant manufacturing capacity to provide multiple long‑term supply alternatives to



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