Gene Therapy, Results

Early data snapshots of Axovant’s gene therapies for Parkinson’s, Tay Sachs appear promising

Following the collapse of its neuro-focused strategy, Axovant’s foray into gene therapies — with their potential for one-shot, long-term cures — has generated considerable interest. On Monday, the biotech provided an early positive snapshot of two of its programs: in Parkinson’s and infantile Tay-Sachs disease.

Two patients were given the lowest dose of Axovant’s Parkinson’s gene therapy — AXO-Lenti-PD — as part of a mid-stage study called SUNRISE-PD. Patients were assessed three months after their dose, having been washed out of their oral levodopa therapy — the gold standard treatment for Parkinson’s. On a physician-rated scale (UPDRS) assessing motor function (the Part III score), both patients experienced an improvement. The scale measures scores ranging from 0 to 108, with lower scores indicating improvement. At three months, one patient saw an improvement of 14 points, the other 36 points — translating to an average improvement of 25 points or a mean 42% from baseline, Axovant said.

Gavin Corcoran

Progress was also observed on other parts of the UPDRS scale. In activities of daily living (UPDRS Part II), patients experienced an average improvement of 22 points from baseline, while for complications of therapy (UPDRS Part IV), they saw a mean improvement of 7 points from baseline.

Axovant licensed the investigational gene therapy, as well as the predecessor product ProSavin, from Oxford BioMedica last year for $30 million upfront. AXO-Lenti-PD is designed to deliver three genes — tyrosine hydroxylase, cyclohydrolase 1, and aromatic L-amino acid decarboxylase — via a lentiviral vector to encode a set of critical enzymes required for dopamine synthesis to restore steady levels of dopamine in the brain in one shot.

These results suggest that the lowest dose of AXO-Lenti-PD at three months may have greater efficacy compared to the highest dose of ProSavin previously tested, Axovant said.

Roger Barker

“The mechanism of action of AXO-Lenti-PD…as well as our prior clinical experience with ProSavin, led us to expect that the major benefit would be in improving the OFF state – and the results so far are very encouraging in this regard,” said Roger Barker, one of the principal investigators on the SUNRISE-PD study.

Based on feedback from the data monitoring committee, Axovant is going to test a second dose of the therapy, and the first administration of that new dose is expected in the second quarter, the company said.

Axovant also provided an early look into the three-month data for its gene therapy for advanced infantile Tay-Sachs disease, a rare and fatal pediatric neurodegenerative genetic disorder with no approved therapies.

The therapy — AXO-AAV-GM2 — is designed to restore β-Hexosaminidase A enzyme activity in the central nervous system (impaired activity of this enzyme causes Tay-Sachs) and was given to an advanced 30-month old patient.

It was generally well tolerated and the patient’s clinical condition was deemed stable three months following administration.

β-Hexosaminidase A activity was determined using a standard assay. At baseline, the patient’s enzyme activity in the cerebrospinal fluid was 0.46% of normal, but after three months there was an apparent increase in enzyme activity to 1.44% of normal, eclipsing the 0.5% threshold that could represent a clinically relevant effect, Axovant underscored.

“This is the first time a gene therapy has been administered to a child with Tay-Sachs disease, and it is remarkable that we have not only seen good safety and tolerability to date, but also evidence of functional β-Hexosaminidase A enzyme activity,” said Gavin Corcoran, Axovant’s executive VP of R&D.

Initial data for both gene therapies are promising, but only time will tell how effective, durable and safe their use is.

“AXGT should be considered amongst the other gene therapy players in the space (e.g., MGTX, VYGR, SGMO, etc. which all trade at 2-5x higher market caps. (1) For their Parkinson’s disease gene therapy, new data today demonstrating an average +42% improvement in UPDRS PART III and improvement in dyskinesia is solid and beat expectations and looks at least as good already or better than other programs and the company plans to dose patients at a higher dose in Q2, setting the program up to be a rival to VYGR’s (Voyager’s) recently partnered AAV-based gene therapy. (2) We think the data for Tay Sachs disease are also compelling and suggest the potential for disease modification,” Jefferies’ Michael Yee wrote in a note.

Shares of the New York-based company $AXGT jumped more than 28% to $1.90 in premarket trading. Axovant is one of the various drug developers created and championed by former hedge fund player Vivek Ramaswamy under his umbrella Switzerland-based company Roivant.


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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
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