Axovant reaps the rewards from its gene therapy refocus

Axovant is the latest company to benefit from excitement over gene therapy data in small numbers of patients.

Axovant’s rebranding as a gene therapy company appears to be paying off already, at least as far as its share price is concerned. The group was up as much as 50% this morning after releasing data from just three patients treated with two of its candidates: AXO-Lenti-PD in Parkinson’s and AXO-AAV-GM2 in Tay-Sachs disease.

Still, the company is well off highs seen in 2017 before its Alzheimer’s disease candidate intepirdine flunked its phase III trial. Axovant has a long way to go – and a lot more patients to treat – before its reinvention can be classed as an unqualified success.

Better than Prosavin?

The bigger dataset released by Axovant today involved just two subjects treated with AXO-Lenti-PD in the low-dose cohort of the Sunrise-PD trial.

Axovant licensed the lentiviral project from Oxford Biomedica last June, marking the first of several deals to bring in gene therapy assets (Axovant looks to Oxford Biomedica for gene therapy resurrection, June 6, 2018).

AXO-Lenti-PD is said to be tenfold more potent than Oxford’s failed first-generation Parkinson’s gene therapy project, Prosavin, by spurring increased production of dopamine, the neurotransmitter that is depleted in the disorder.

Axovant today said the latest data suggested that AXO-Lenti-PD had greater biological activity than Prosavin. However, this should be taken with a pinch of salt: as well as the small number of patients treated, the claim was based on a cross-trial comparison, and these should always be treated with caution.

Nevertheless, Axovant highlighted differences in various components of the unified Parkinson’s disease rating scale (UPDRS) “off” score at three months with low-dose AXO-Lenti-PD in Sunrise-PD versus the highest dose of Prosavin given in its phase I/II trial.

For example, there was a 55-point improvement from baseline in total “off” score in the two patients receiving AXO-Lenti-PD at 4.2x106 transducing units (TU), versus an 18-point improvement in six patients given Prosavin at 1.0x108 TU. TUs are used to quantify doses of lentiviral vectors specifically, as opposed to the vector genome units used for AAV vectors.

Axovant plans to begin dosing a second cohort of AXO-Lenti-PD, at 1.4x107 TU, in the second quarter, so it might be prudent to wait for more data before hailing the project as a winner. Sunrise-PD is set to enrol 30 patients in total, according to


If the AXO-Lenti-PD data were hard to interpret, the results with AXO-AAV-GM2 were even trickier, coming in just one patient with Tay-Sachs disease, a fatal inherited neurodegenerative disorder that affects babies and young children.

Axovant gained the asset through a deal with the University of Massachusetts Medical School in December (Two more gene therapies for Axovant, 14 December 2018). AXO-AAV-GM2 is designed to increase the activity of the β-hexosaminidase A (hex A) enzyme, which is reduced in Tay-Sachs, leading to the build-up of toxic gangliosides in neurons.

The 30-month old subject received AXO-AAV-GM2 at 1.0x1014 vector genomes. At three months Axovant said the patient’s condition had not deteriorated, based on a neurological exam and MRI scanning pre and post-treatment.

The company added that levels of the hex A enzyme had increased to 1.44% of normal at three months, and suggested that 0.5% could be the threshold for a clinically meaningful effect.

Again, this will need to be replicated in more patients, and today’s share price reaction looks like over-optimism among Axovant investors. Or perhaps the company, whose stock was worth just $1.48 on Friday, is cheap enough to take a punt on. Today's rise lifts its market cap to $308m. 

Either way, Axovant’s change of focus, with relatively little initial outlay, looks to have been a good move. If the company wanted to generate excitement with data in just a handful of patients then in gene therapy it chose the right area.

Axovant's gene therapy pipeline
Project Indication Originator Cost
AXO-Lenti-PD  Parkinson's disease Oxford  Biomedica $30m up front
AXO-AAV-GM2 Tay-Sachs & Sandhoff diseases  University of Massachusetts Medical School Undisclosed
AXO-AAV-GM1 GM1 gangliosidosis University of Massachusetts Medical School
AXO-AAV-OPMD Oculopharyngeal muscular dystrophy Benitec   $10m up front
AXO-AAV-ALS Amyotrophic lateral sclerosis Benitec  
AXO-AAV-FTD Frontotemporal dementia Benitec  
Source: Company website, news releases.

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