From a reported ovation at a medical conference to the smashing of sales forecasts, events this week confirm that the treatment of spinal muscular atrophy is under radical transformation.
For companies at the forefront of research, however, improving fortunes are harder to pin down. Biogen is clearly leading the field with the recently approved Spinraza, but the threat of gene therapy is growing. Should its main competitor, Avexis, receive good news from the FDA in the coming months, its position could be weakened.
Both were out in force at the American Academy of Neurology meeting this week, though Avexis stole the show with a presentation of its phase I study of AVXS-101. The gene therapy seeks to correct the genetic fault responsible for the devastating wasting disease.
A video of children with SMA type-1, the most severe form, walking around unaided apparently had the audience applauding; these children typically do not achieve any major motor milestones, and never manage to sit unaided. Most die by the age of two.
In the trial 15 type-1 children remained event-free – death or requiring full time respiratory assistance – at 13.6 months of age, the cutoff for the primary analysis. Of these 12 were given the proposed higher therapeutic dose – at data cutoff five could sit unassisted, with evidence of others reaching this milestone after the evaluation date. Most of these achieved motor milestones like head control and the ability to roll.
Durability remains a big question for AVXS-101, and there are reasons for caution: four children needed new respiratory or nutritional assistance after dosing, hinting at deterioration. The company defended these cases individually on a conference call and pointed out that their overall performance was still much improved from a typical type-1 child.
The next step for Avexis is agreeing the design of a pivotal trial, which the company wants to start this quarter. A meeting with the FDA in May will help finalise this – a green light for a single-arm study would be a big win.
However, the picture is complicated by the availability of Spinraza. The FDA approved the antisense therapy with a broad SMA label late last year though its high cost prompted payers to limit its use to the most severe patients, generally those who develop symptoms before six months of age (Payers threaten a hard-knock life for orphan projects, 25 January 2017).
The issue of using these agents in combination is now a live one – it seems unlikely that the FDA would demand such an enquiry in Avexis’s pivotal trial, but the existence of a new standard of care complicates the situation.
Yesterday Biogen presented full data from the phase III Endear trial, which recruited 121 patients up to seven months old. It classified 51% of them as motor milestone responders at the end of the study, versus zero among the placebo arm, with infants demonstrating continuing improvement.
Tomorrow the company will present data from the phase II Nurture trial, which recruited babies under six weeks old. The abstract suggests that the interim results will confirm that treating earlier can improve results – the same seems to hold for AVXS-101.
First-quarter Spinraza numbers released yesterday reveal huge demand for the product and presumably a willingness to pay for it, despite the pushback. Sales reached $47m against expectations of around $13m. Sellside analysts are pencilling in peak revnue of around $1bn, a figure that could rise if the drug continues to demonstrate improving responses and takeup in in less severe types of the disease.
However, AVXS-101 is also a big threat to this figure. True, the gene therapy is unlikely to reach the market until 2019, and it still has to replicate its results in phase III. The risks inherent in gene therapy development are also huge. And it must demonstrate durability of response, though again this is arguably more of an issue for payers than for regulators.
Still, Biogen’s announcement that it will be pushing its own SMA gene therapy into the clinic next year is perhaps recognition of a greater potential.