Chasing Biogen, AveXis posts improved gene therapy data

All except one of the children who received the larger dose of AVXS-101 are now sitting unassisted.

AveXis has posted an update on the spinal muscular atrophy (SMA) patients treated with its gene therapy. The latest data show an uptick in the proportion of patients able to sit unassisted and talk, fueling AveXis’ hopes of establishing AVXS-101 as a rival to Biogen’s Spinraza.

Chicago-based AveXis reported the updated data, which cover the period up to early August, in a paper in the New England Journal of Medicine. The results include areas in which the patients have improved in the eight months since the cut-off date for the previous data drop. That earlier readout was encouraging enough to prompt AveXis to commit to a pivotal trial.

The latest data validate that decision. As of August, 11 of the 12 patients who received the larger dose of the gene therapy were able to talk, as compared to 8 out of 12 at the previous readout. The number of patients who can sit unassisted has ticked up from seven to nine. And AveXis has seen a jump in the number of patients who can sit unassisted for 30 seconds. 

These are big milestones for children who have historically had poor prognoses and no treatment options. Biogen gave kids with the degenerative motor neuron disorder some hope in 2016 when it picked up approval for its Ionis Pharmaceuticals-partnered Spinraza. The Big Biotech slapped a $750,000 price tag on the drug’s first year of use, making it one of the most expensive therapies.

AveXis is now closing in at a shot at disrupting Biogen’s nascent franchise. NEJM published the AveXis data on the same day as a separate paper detailing the results from a placebo-controlled phase 3 trial of Spinraza. The differences in the inclusion/exclusion criteria make comparisons between AveXis' study and that trial unreliable.

In the NEJM paper, 8% of the patients who received Spinraza were able to sit unassisted. The figure (PDF) is far higher when Spinraza is given to patients with presymptomatic SMA. But the totality of clinical data posted to date still suggest AveXis could pose a real threat to Spinraza.

RELATED: AveXis SMA gene therapy advances toward pivotal trial

That has opened the door to AveXis’ hustling AVXS-101 through the rest of development and the approval process in the U.S. and Europe quickly.

“Both of the regulatory agencies have agreed that the ... confirmatory trials for SMA Type 1 would be a single arm utilizing natural history as the control with relatively few patients, 15 or 20 in the U.S. and approximately 30 in EU. And they have each asked us to seek discussion with them to talk about accelerated approval or conditional approval,” AveXis CEO Sean Nolan said on a conference call with investors earlier this year.

If AveXis succeeds in bringing AVXS-101 to market it will face the question of how to price its potential one-shot treatment for SMA against Biogen’s expensive, ongoing treatment. 

That question is complicated by uncertainty over whether expression of the gene therapy will wane with time, forcing healthcare systems to payout again after thinking they had already bought a one-shot treatment. In that situation, the patient may have developed antibodies against AAV capsid proteins, removing the option of administering AVXS-101 again.

Ans van der Ploeg, M.D., Ph.D., a researcher at Erasmus MC University, sketched out that scenario in a NEJM editorial discussing the “dilemma” created by the development of two innovative drugs against SMA. That dilemma is, of course, preferable to the previous situation in which patients had no access to innovative drugs.

Editor’s Note: This story has been updated to clarify the differences in trial design between the AVXS-101 and Spinraza studies and their impact on the comparability of the data.