Up until this point, studies of an experimental drug from Biogen and Ionis Pharmaceuticals had focused on patients with the most severe form of a rare, potentially deadly genetic disorder called spinal muscular atrophy. But new data released this morning show that the therapy, known as nusinersen (Spinraza), could have a much broader reach.
Biogen (NASDAQ: BIIB) and Ionis (NASDAQ: IONS) said this morning that nusinersen met its main goal in a Phase 3 study in patients with later-onset, or Type 2 SMA. Patients on the drug, the two companies said, had a statistically significant improvement in motor function compared to those who took placebo. As a result, Biogen and Ionis will stop the study early and give all patients the option to transition to a different, open-label extension trial called Shine so they can all get the drug.
SMA is caused by a faulty version of the SMN1 gene, which doesn’t end up producing enough of the SMN protein to keep muscles strong. The disease affects about one out of every 10,000 newborns. There are four different forms of SMA, types 1 through 4, characterized by their severity and when they are diagnosed. Type 1 is the most severe and common form, diagnosed within six months of birth, and it can stop children from ever being able to walk or even sit; patients with this form of the disease often die within a few years due to complications such as respiratory problems. Type 3 SMA patients, by comparison, can live full lives, but may lose the ability to stand and walk.
There are no approved drugs for SMA, but nusinersen has a chance to be the first. It’s an RNA-based drug meant to help boost production of the SMA protein, which in turn is supposed to help improve patients’ motor function.
In August, Biogen and Ionis reported positive data from a trial in infants with type 1 SMA and, as with its news today, stopped that study so that patients could transition to an open-label extension study and get nusinersen. Biogen also paid $75 million to exercise an option to worldwide rights to the drug.
Biogen recently filed for approval of nusinersen in both the U.S. and Europe, and plans to submit paperwork in other countries in the coming months. One of the questions surrounding the drug, however, has been just how much of the SMA patient community it could impact. About 25,000 people in the U.S. have SMA, and a majority of those diagnosed every year have Type 1. But patients with Type 2 SMA—diagnosed between 6 months and two years of age, as opposed to in infancy—have a better prognosis than Type 1 patients. Type 2 patients, for instance, might not be able to walk, but they can sit upright, function with the help of a wheelchair, and live longer.
As a result, there are more patients living with Type 2 SMA than Type 1. Evercore ISI analyst John Scotti wrote in a research note this morning that an estimated 2,500 patients in the U.S., Europe and Japan have Type 1 SMA, while about 10,000 in those countries have Type 2. The possibility that nusinersen could be a broadly used therapy is one of the reasons today’s study is so important for SMA patients.
“With these new results added to the totality of the data, it will build the argument to support the broadening of the drug label, and coverage, out even further,” said Kenneth Hobby, the president of nonprofit group Cure SMA, in an e-mail to Xconomy.
Hobby said Biogen now has two trials with positive data on nusinersen, increasing the likelihood that the results aren’t just due to chance. Plus, since the data are from a placebo-controlled trial, which the FDA prefers, “it will carry greater weight with the FDA, specifically in the older and less severe types.” That’s critical to getting the “broadest label possible” for nusinersen, Hobby said. (Cure SMA drew about 4 percent of its $5.4 million in funding in fiscal 2015 from corporate supporters, some but not all of whom are drug makers. It also helped fund the nusinersen program in 2003 when it started out as research at the University of Massachusetts, before it was licensed to Ionis.)
Biogen enrolled 126 patients in the study; 84 got nusinersen while 42 got a placebo. After 15 months of treatment, the two groups demonstrated an average difference of 5.9 points on the Hammersmith Functional Motor Scale (HFMS), a survey used to evaluate the motor skills of SMA patients. Biogen said that patients on nusinersen had an average improvement of 4.0 points on the HFMS, while those on placebo declined by an average of 1.9 points. A change of three points or greater is clinically meaningful, Biogen said.
No patients dropped out of the study. The majority of side effects were either considered related to patients’ SMA or to the lumbar puncture needed to administer nusinersen. Biogen didn’t provide any more details on the data or the side effects. More data will be presented at a future medical meeting.
Biogen is preparing to potentially launch nusinersen in the U.S. as early as by the end of the year.
“We will make regulators around the globe aware of this data and will continue working closely with them to bring [nusinersen] to families affected by SMA as quickly as possible,” said Biogen research chief Michael Ehlers, in a statement.
Shares of Biogen climbed more than 5 percent in early trading on Monday. Ionis shares rose more than 18 percent.