Spinal muscular atrophy affects over 25,000 people in the U.S. and stops many of them from ever being able to walk. Yet scientists’ understanding of the underlying genetic cause of SMA is fairly recent, which is why drugs for the disease are only now progressing through the pipelines of biotech and pharma companies.
The most advanced of those therapies is a treatment developed by Carlsbad, CA-based Ionis Pharmaceuticals, and today that drug, known as nusinersen, took an important step forward.
Ionis (NASDAQ: IONS) and its partner, Cambridge, MA-based Biogen (NASDAQ: BIIB), this morning reported an interim look at an ongoing Phase 3 study of nusinersen—an RNA-based drug meant to help treat patients with SMA. The drug, the two companies said, has met the trial’s primary goal. In infants with type 1 SMA—the most common and severe form, affecting about 60 percent of patients with the disease—led to a statistically significant improvement in helping patients achieve certain motor milestones, compared to a placebo.
Neither company provided any specifics beyond the announcement, though Biogen said it will present the data in detail at a future medical meeting. Biogen also said that because of the data, it will stop the ongoing study, a 122-patient, placebo-controlled trial known as Endear, early. Patients in this study and another placebo-controlled Phase 2 trial called Embrace can transition onto an open-label extension study known as Shine, in which all patients will get nusinersen.
Additionally, Biogen has paid Ionis $75 million to exercise its option to worldwide rights to nusinersen, meaning Biogen will pay for all the remaining clinical, regulatory, and commercialization work. Ionis will complete the ongoing Phase 3 studies before transitioning everything to Biogen. Ionis can get up to $150 million in downstream payments tied to regulatory milestones, and would get royalties on any sales of nusinersen.
In the coming months, Biogen will begin preparing regulatory filings. That, in itself, would be a milestone, considering there are no SMA therapies that have made it to the feet of the FDA, let alone won approval.
“Today is a hopeful day for the SMA community, which has worked tirelessly to support research and development for this terrible disease,” said Kenneth Hobby, the president of non-profit patient advocacy group Cure SMA, in a statement. “We are excited about reaching this important milestone, and the opportunity these results create to potentially bring the first treatment option for SMA to patients and families.”
Biogen chief medical officer Al Sandrock added: “We share the community’s sense of urgency as we strive to bring the first treatment for SMA, the leading genetic cause of infant mortality, to families facing this devastating disease.”
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, and kill them 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.
Nusinersen is an RNA-based drug meant to help boost the production of the SMN protein, which in turn is supposed to help improve patients’ motor function. Cure SMA helped fund the drug program in 2003 when it started out as research at the University of Massachusetts, before it was licensed to Ionis.
Nusinersen isn’t a cure for SMA, and several other companies are developing different types of therapies meant to attack the disease in one way or another. Both AveXis (NASDAQ: AVXS) and Voyager Therapeutics (NASDAQ: VYGR), for instance, have gene therapies in development meant to provide a long-lasting treatment for SMA; AveXis’s treatment is in Phase 1 testing, while Voyager has yet to begin clinical trials. Roche, Cytokinetics, and Novartis each have experimental drugs with different approaches that are in mid-stage trials.
Overall, 14 companies overall are investing in SMA programs, compared to zero in 2000, according to data from Cure SMA. That’s a reflection of the relatively new understanding of what causes the disease. The SMN1 gene, for instance, was cloned in the 1990s, and additional information about its role, and the development of animal models, helped bring development along.
Biogen and Ionis are evaluating nusinersen in several different SMA settings. In addition to the Phase 3 trial reported on today, the two companies have another late-stage study going in patients with later-onset SMA, between the ages of two and 12, and have another trial of nusinersin in infants who haven’t yet displayed symptoms. RBC Capital Markets analyst Michael Yee wrote in a research note that nusinersen could represent a “theoretical $1 billion-plus franchise” when including all the other patient groups the drug is being studied for. Yee estimates that there are roughly 700 type 1 infants diagnosed, worldwide, every year.
Shares of Ionis surged nearly 39 percent in pre-market trading on Monday, while Biogen shares climbed just over 4 percent. The two companies will hold a conference call this morning to discuss the results.