Axovant trumpets new clinical data after gene therapy pivot

Axovant has a pair of clinical readouts from its switch into gene therapy after failed endeavours in Alzheimer’s disease—and the initial data look encouraging.

The two studies, in Parkinson’s disease and neurodegenerative genetic disorder GM2 gangliosidosis or Tay-Sachs disease, involve a tiny number of patients but suggest the therapeutic genes are being delivered effectively, with no serious side effects, and with early evidence of activity.

First up, Axovant has reported data from two patient treated with the lowest planned dose of its AXO-Lenti-PD gene therapy for Parkinson’s, with the headline news an average 25-point (42%) improvement in the widely-used Unified Parkinson’s Disease Rating Scale (UPDRS) Part III OFF score of motor function after three months.

That is a greater improvement than was seen with the highest dose of an earlier, less-potent form of the gene therapy—called ProSavin—that was put through its paces several years ago and generated considerable excitement about the prospects for gene therapy in Parkinson’s.

The initial readout comes from the phase 2 SUNRISE-PD trial of AXO-Lenti-PD and showed that the one-shot therapy seems to be was as well-tolerated as ProSavin but has “substantially greater biological activity,” according to Axovant’s head of R&D Gavin Corcoran, who joined the company last year from Allergan.

As well as the top-line UPDRS score, there were also improvements across the board in UPDRS OFF subparts, which give an indication of the efficacy of the gene therapy after oral levodopa has been washed out of the patients’ systems.

One of the investigators in the trial, Roger Barker, Ph.D., of the University of Cambridge and Addenbrooke's Hospital in the UK, said the mechanism of action of the gene therapy “led us to expect that the major benefit would be in improving the OFF stateand the results so far are very encouraging in this regard.”

AXO-Lenti-PD delivers three genes involved in the synthesis of dopamine, the neurotransmitter that is deficient in Parkinson’s disease.

Axovant licensed ProSavin and AXO-Lenti-PD from UK biotech Oxford Biomedica last June for an upfront fee of $30 million and up to $812 million in additional payments, plus royalties on any eventual sales. The company now plans to start dosing patients in the second, higher dose cohort in the second quarter.

The second readout comes from a single, 30-month-old patient with infantile Tay Sachs in a phase 1/2 investigator-led trial, who received partial therapy with Axovant’s AXO-AAV-GM2 candidate.

The subject was given a partial treatment with the gene therapy, with injections into the spinal column and cisterna magna area of the brain, but without a third administration into the thalamus because of the child’s advanced disease. AXO-AAV-GM2 delivers the gene for β-hexosaminidase A, an enzyme deficient in Tay Sachs.

After three months the patient’s clinical condition was stable with no evidence of neurological deterioration and there was an increase in the level of β-hexosaminidase A in the cerebrospinal fluid, suggesting the therapy was working as expected. The increase was above the threshold that the investigators believe could be enough to have a clinically important effect.

“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 Corcoran.

Axovant’s new CEO Pavan Cheruvu, M.D., is presenting the data today at the Cowen and Co health care conference.

In gene therapy trials, even tiny updates on a handful of patients are watched with great interest and can lead to big stock swings, and Axovant was no exception this morning with a 45% increase pre-market after the results were announced.

The positive data marks the continued renaissance for Axovant after a torrid couple of years punctuated by serial failures for its repurposed small-molecule drugs for neurological disorders. Later this year, the company is also due to report results of a third gene therapy candidate—AAV-GM1 for GM1 gangliosidosis—with the first patient scheduled to be treated in the coming weeks.

Last month, analysts at Jefferies said that Axovant’s stock was “poised to bounce” this year on the strength of the three trial readouts.