Four months after its drug nusinersen (Spinraza) became the first ever approved to treat the rare genetic disease spinal muscular atrophy, Biogen (NASDAQ: BIIB) released study results Tuesday that could help more patients gain access to the expensive drug.
The data, from a 126-patient study called CHERISH, provide the most detailed evidence to date that nusinersen can benefit patients with multiple forms of SMA, a degenerative muscle disease that can rob people of their ability to walk and function independently. Neurologists who treat SMA patients were positive about the data, but believe more lengthy testing is needed to see the drug’s true long-term benefit on patients with milder forms of the disease.
Xconomy last week detailed the stories of SMA patients whose families have battled insurance companies and medical centers, despite the FDA’s December approval of nusinersen for a broad population.
On an earnings call early Tuesday, Biogen reported nusinersen sales for the first time. They were higher than analysts expected. CEO Michel Vounatsos acknowledged, however, that “bottlenecks remain.”
Much of the difficulty patients—mainly children and young adults—are experiencing with access to nusinersen stems from the high list price: $750,000 for the first year, and $375,000 each year thereafter. (The drug must be taken chronically.)
The FDA approved nusinersen for children and adults with all forms of the disease, but several insurers have said they first want to see published data in patients with certain types of SMA before approving coverage.
Treatment centers have also faced logistical struggles stocking the drug and preparing for the complicated procedures required to administer it.
Biogen reported $47 million in first-quarter revenue, well beyond analysts’ $15 million consensus estimates. Biogen could soon roll out the drug in other countries. Nusinersen could be approved in Europe, Japan, and Canada this year, and the company is filing for approval in 10 more countries.
On the call, several Biogen executives said data presented at the American Academy of Neurology’s annual meeting on Tuesday could help convince payers to loosen their coverage restrictions.
Until Tuesday, the most significant published data covered Type 1 patients, who are diagnosed in infancy and often die at an early age. The CHERISH study enrolled patients diagnosed between the ages of 2 and 12, whom Biogen describes as “likely to develop” Type 2 and Type 3 SMA. (There are five types in all, 0 to 4.) Type 2 progresses more slowly, though patients might never be able to walk. Type 3 patients can walk initially before losing strength later in life.
Vounatsos said Tuesday that a majority of patients treated so far have Type 1. CHERISH might help change that. “It is our hope this new data will convince the payers who have developed narrow medical policies to offer broader access to patients,” Vounatsos said.
Biogen CFO Paul Clancy estimated that 75 percent of U.S. insurance plans have approved nusinersen for at least some people with SMA. About half of those insurers have a “narrow” policy that could be impacted by new data, Clancy said.
Biogen enrolled 126 patients in the study; 84 received nusinersen while 42 received a placebo. When nusinersen was approved in December, Biogen had only interim results. They showed a clinically meaningful difference in motor function after 15 months between the drug and placebo groups (an average of 5.9 points on the Hammersmith Functional Motor Scale).
With CHERISH completed, Biogen has updated that figure. The average difference between the two groups is now 4.9 points, largely due a change in the placebo group’s average decline. Slides from the presentation at AAN show that more than half the patients on nusinersen (56.8 percent) were deemed “responders,” meaning at least a 3-point improvement on the Hammersmith scale; 26.3 percent of placebo patients showed that level of improvement.
“This has incredible significance for these patients,” says Timothy Lotze, a pediatric neurologist at Texas Children’s Hospital who wasn’t associated with the CHERISH study. “These kids not only met an outcome of statistical significance but also of functional significance, which probably translates even more to real world outcomes.”
The positive change on the Hammersmith scale was the main goal of the study. But details from the drug’s secondary measures were mixed. For example, 19.7 percent of patients achieved a new motor milestone after 15 months, compared to 5.9 percent on placebo, but the results weren’t statistically significant. Other secondary measures calculating the ability to stand alone or walk with assistance also failed to meet statistical significance.
Lotze says those gains are still meaningful, considering how old these patients were and how far along their disease was when the trial started. But others disagree.
“Those are the things we ultimately care about more,” says Alexander Fay, a pediatric neurologist and neuromuscular specialist at UCSF Benioff Children’s Hospital in San Francisco, CA, who also wasn’t involved with the trial.
Fay says while CHERISH shows that nusinersen helps Type 2 and Type 3 SMA patients, the study was too short to understand the magnitude of the benefit. Fay still wants to know how it will impact patients in the long term, such as their breathing problems or the spinal curvature that many develop. How significant will the positive effects be, he asks, and will any side effects emerge?
“There’s definitely reason to be optimistic,” he says, ”but we just don’t know yet what the impact is going to be.”
Biogen touts the drug’s safety profile, and clinicians interviewed by Xconomy mainly agree. They say the most common side effects so far are headaches and pain related to the lumbar puncture used to administer nusinersen. Taken together, will the data be good enough for payers to change their policies? “It’s going to create increased pressure and momentum for all children with different types of SMA to be treated, and to be treated as early as possible,” Fay says.
Lotze says he hopes there will be an impact on policies, but expects insurers—as many already have—to demand proof over time that the drug is working to continue treatment.
Analyst Geoffrey Porges of Leerink Partners believes the results leave wiggle room for insurers to “push back on approving Type 2’s and older adolescents and adults” given the “less than spectacular motor milestones results,” he wrote in a note to investors.
As Xconomy has detailed, some frustrated patients and their families have had to wait months before receiving treatment. Others are still awaiting insurance coverage. Treatment centers in California (Stanford University), Pennsylvania (Children’s Hospital of Philadelphia) and New Jersey (Goryeb Children’s Hospital) reported to Xconomy that a minority of their patients had started on drug so far, with many tied up with payers. Biogen CEO Vounatsos said Tuesday that while some “leading” centers have treated more than 10 patients, most have only dosed one or two.
Biogen also said 100 commercial plans and 65 Medicaid plans have approved “individual cases” of nusinersen, that 88 sites in 36 states have administered it, and 203 total sites have submitted “start forms,” which patients fill out to try to gain access to the drug.
A treatment delay can be critical. For a small child with SMA, getting nusinersen could mean more time being able to sit up, stand, or walk. What’s more, patients tend to respond better if they’re treated quickly after diagnosis, says Wildon Farwell, a senior director of medical development at Biogen. “The data are just quite clear across the program that that is in the best interest of the patients,” he says.
Nusinersen’s launch is critical for Biogen, which has no other near-term commercial opportunities in its pipeline. Biogen’s most advanced experimental treatment, aducanumab, won’t produce Phase 3 data until 2019 in the high-risk field of Alzheimer’s disease, which is littered with late-stage failures.
Meanwhile, revenue from the company’s core franchise of multiple sclerosis drugs is flattening, and more competition is on the way, chiefly from a new MS drug from Roche/Genentech, ocrelizumab (Ocrevus).
“It’s a battle every day, and it’s not yet where we want to be,” Vounatsos said of nusinersen’s launch.