SMA Day: AveXis Gene Therapy Creeps Forward as Biogen Drug’s Sales Slow

Xconomy Boston — 

Just a few years ago, there were no drugs available for patients with the rare genetic disease spinal muscular atrophy. Now two cutting-edge therapies look headed for a commercial battle, with each data and revenue update a key moment in the race.

Biogen (NASDAQ: BIIB) was the first to bring an SMA drug to market, the RNA drug nusinersen (Spinraza), a chronic treatment that has shown an ability to help people with multiple forms of the progressive disease. But sales of the landmark drug are slowing, and there is pressure building from rival AveXis (NASDAQ: AVXS), the Chicago-based developer of a gene therapy that Novartis just agreed to buy for a whopping $8.7 billion. If all goes well, the gene therapy could be on the market next year.

The latest updates came from both companies during the American Academy of Neurology’s meeting in Los Angeles. AveXis gave people the first look from a key clinical study and updated a previous one. And Biogen offered a look at an ongoing open-label extension study of nusinersen and revealed the drug’s latest sales numbers.


This is the first time Avexis has disclosed information about STR1VE patients, who all have the most severe form of SMA, type 1. Kids who inherit the disease could die by the age of two. More moderate forms of SMA rob people of their ability to walk and function independently.

STR1VE is a pivotal trial, which means it is designed to be the final piece of the clinical puzzle before an FDA approval decision. Plans call for 15 patients total to be enrolled and treated with a one-time dose of Avexis’s AVXS-101. The study’s main goals are for patients to survive through 14 months of life and, in that time, to breathe without the aid of a ventilator for 14 straight days (what’s known as “event-free” survival); and for patients to be able to sit, independently, at 30 months of age.

At AAN, AveXis reported that 11 patients had been dosed as of April 11 and six of them had taken the gene therapy at least a month ago. All six of those patients, thus far, have met the study’s goals. They’ve also seen their scores improve on a test, CHOP-INTEND, that evaluates motor function. In an earlier study of the AveXis therapy, patients’ CHOP-INTEND scores increased by an average of 9.8 points after one month and 15.4 points after three months. Thus far in STR1VE, the six patients’ scores jumped by an average of 7.8 points after one month and 17.3 points (in three patients) after three, AveXis said.

No serious side effects have been reported thus far. AveXis said two patients had a spike in liver enzymes that didn’t lead to problems and was reversed with a short course of steroids—a common reaction to gene therapy.

Results from earlier studies of AVXS-101 have been eye-opening, and no major safety problems have yet emerged. AveXis also updated those studies at the neurology meeting with results in patients after at least two years of follow-up.

AveXis said that after two years, all 15 patients in the study are alive and don’t need a ventilator. Those patients are a median of 27.8 months (given a low dose) or 30.7 months (given a high dose) old. Citing natural history studies, AveXis said 8 percent of untreated patients with SMA type 1 are event-free after 20 months.

One safety question hanging over the gene therapy field relates to the way the therapy enters patients’ cells. A pioneer in the field, James Wilson of the University of Pennsylvania, caused a stir early this year by publishing a paper citing concerns with testing high doses of a certain kind of gene therapy which rides into cells in the shell of an adeno-associated virus, or AAV.

Several others in the field, including the doctor leading AveXis’s Phase 1 study, pushed back against those concerns in interviews with Xconomy.

Patients in the AveXis study were given high doses of AAV. In an interview earlier this year, Jerry Mendell, the director of the gene therapy center at Nationwide Children’s Hospital in Columbus, Ohio, said the most significant issue was a spike in liver enzymes in four patients that was suppressed with steroids and didn’t lead to any notable side effects, said Mendell.

Mendell said experienced scientists had warned that the doses in the trial would probably be unsafe. But if he and his team hadn’t tested high doses, “we wouldn’t have saved lives and wouldn’t have had patients walking.”

Today’s update did not change that. AveXis didn’t report any new safety concerns. It also just started a trial, SPRINT, testing AVXS-101 in patients with multiple forms of SMA.


There were no treatments for SMA until December 2016, when the FDA approved nusinersen. The drug, an RNA-based therapy administered through a spinal infusion a few times a year, was a medical breakthrough. It may slow the progression of multiple types of SMA and must be taken for life.

Yet nusinersen, which generated $884 million worldwide for Biogen (NASDAQ: BIIB) in fiscal 2017, has limitations. Neither … Next Page »

Single PageCurrently on Page: 1 2