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This is a big moment for people diagnosed with spinal muscular atrophy, or SMA, a rare and potentially lethal genetic disorder that destroys muscles. For decades, there was no way to change the trajectory of their disease. They now have one marketed medicine, and this month, chances are theyll have another: a gene therapy that promises a long-lasting treatment, if not an outright cure, through a one-time dose.

This weekend at the annual American Academy of Neurology meeting, patients, their families, and doctors will gain more insight about the gene therapy, Zolgensma, which is owned by drug giant Novartis (NYSE: NVS), and how it might stack up against the approved medicine nusinersen (Spinraza), owned by Biogen (NASDAQ: BIIB). They can also look forward to the latest clinical data from an SMA drug, risdiplam, from Roche, that, if successful, would be the first that a patient could take orallya big deal, because the most severe cases of SMA are in newborns and infants, and Spinraza requires chronic spinal infusions.

Its ridiculously exciting, says Jahannaz Dastgir, a pediatric neurologist at Goryeb Childrens Hospital in Morristown, NJ. Its a great time to be a doctor.

All the new information comes amid anticipation that the FDA this month will approve Zolgensma. With the agencys green light, it would be the second approved gene therapy in the US, and one of just a handful around the world.

Zolgensma will also face something other gene therapies havent: competition. Approved in late 2016, Spinraza has already proven effective and, after early hiccups, has become a big seller for the beleaguered Biogen, with $1.7 billion in sales in 2018 and $518 million in the first quarter of 2019.

Novartis has high hopes for Zolgensma, too, having paid $8.7 billion to buy its developer AveXis in 2018. Its success or failure will be a bellwether for the economics of gene therapy. (Nationwide Childrens Hospital in Columbus, OH, where the therapy was developed, will be watching closely too.)

If both Spinraza and Zolgensma are available, doctors, payers, patients, and their families will face tough medical, logistical, and economic decisions. So far, Spinraza has far more data to support it. But it has a $750,000 first-year price tag and requires a few spinal infusions a year at a $375,000 annual cost thereafter, for life. Zolgensma could cost $1 million or more (Novartis has hinted much more) for a single dose, theoretically a bargain if it saves lives and negates downstream medical and social costs that SMA patients and their families would otherwise face.

A recent survey of 30 physicians in the US and Europe by the investment bank Jefferies suggested that a majority of newly diagnosed SMA patients, as well as those currently on Spinraza, will get Zolgensma. Jefferies predicts $2.6 billion in peak sales for Zolgensma.

Its possible that the best results could come from combination therapy, but that hasnt been tested and the costs would be exorbitant.

Alex Fay, a pediatric neurologist at UCSF Benioff Childrens Hospital in San Francisco, CA, says he would be hesitant to switch patients if Spinraza is well tolerated and working. Adding more complication, says Fay, is the fast progress of the disease. Those decisions are going to have to be made pretty quickly, says Fay.

Information revealed soon could make those decisions easier. Babies diagnosed with Type 1 SMA, the most common and deadly form of the disease, often die before the age of two. Type 2 patients may never be able to walk, while Type 3 patients can walk initially before losing strength later in life. In all types, it seems that the earlier the treatment, the more benefit.

Thus far, all public Zolgensma data have been in babies with Type 1. There will be more of that at AAN. Studies presented at the meeting this weekend will also, for the first time, reveal Zolgensmas effects on more moderate forms of SMA, and in patients who havent shown symptoms yet. Those data could help determine Zolgensmas eventual reach.

More than 7,500 patients across several SMA types have now received Spinraza, some as long as six years. Biogen recently used that experience to turn up the heat on Novartis.

Last week it published results in Neurology, the AANs medical journal, from a long-term study in later-onset patients, aged 5 to 19, who were likely to develop Type 2 or Type 3 SMA. Each group showed improvements on tests of motor function; historical data suggest they should get weaker. A couple patients with Type 3 SMA even regained the ability to walk during the trial, Biogen said.

Citing the study and other data supporting Spinraza, Biogen CEO Michel Vounatsos was adamant on an April 24 conference call that the drug will remain the standard of care for SMA for years to come.

The presentations this weekend will shed more light on the potential benefits and risks of the new world of SMA treatments, but there will plenty of questions left unanswered. Here we break down four key SMA topics that will be under intense discussion.

Fast Access: SMA is a battle against time. Neurons die and dont come back. Muscles waste away and are replaced by scar tissue and fat. The muscle-wasting is particularly fast for babies with Type 1. Time to treatment is of the essence. They may never Next Page

Ben Fidler is Xconomy's Deputy Editor, Biotechnology. You can e-mail him at bfidler@xconomy.com

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