ARTICLE IN BRIEF
Neurologists who treat patients with spinal muscular atrophy discuss the challenges that the newly-approved, high-cost nusinersen presents, and discuss their workaround strategies for making it available to patients.
Until recently, few if any drugs for the treatment of neurologic diseases had achieved the dubious distinction of ranking among the ten most expensive drugs available in the United States in a given year. That's not to say that existing drugs for neurologic conditions aren't costly — the price of multiple sclerosis therapies has continued to increase over the years, for example, and in March 2017, the Food and Drug Administration (FDA) approved ocrelizumab (Ocrevus), the first disease-modifying treatment specifically for primary progressive multiple sclerosis (PPMS), which has a price tag of approximately $65,000 before any negotiated discounts.
In 2017, however, neurology burst onto the list of most expensive drugs in a big way. When nusinersen (Spinraza) was approved by the FDA just before the end of 2016 as the first disease-modifying treatment for spinal muscular atrophy (SMA), it was with an average cost of $750,000 for the first year of therapy, and $375,000 for every year after that. (Patients receive four doses of nusinersen intravenously in the first two months of therapy, then a maintenance dose every four months after that, which accounts for the higher cost in the first year.)
And unlike most cancer drugs, which are usually prescribed for a limited amount of time (typically less than a year), nusinersen will be taken indefinitely. If the cost remains the same, it's estimated that an infant who begins therapy with nusinersen this year will incur $2.25 million in drug costs by the time he or she reaches kindergarten age. How long the drug retains its effectiveness remains unclear, although the trials show that children who began receiving the drug as infants are still benefiting as long as four years later. It's also unknown whether or not, since SMA is to some extent a disease of development, the drug could possibly be reduced or withdrawn when a child gets older.
THE NUMBERS GAME: WHO WILL BENEFIT?
Other new drugs for neurologic diseases have some shocking price tags as well. Cerliponase alfa (Brineura), approved in April to treat the rare, fatal inherited nervous system disorder Batten disease, has a list price of $702,000 — and that doesn't go down after the first year of therapy. Eteplirsen (Exondys 51), approved last year to treat a subset of patients with Duchenne muscular dystrophy, costs $300,000 per year.
But both Batten disease and Duchenne muscular dystrophy are relatively rare: Batten disease and related conditions occur in two to three of every 100,000 live births in the United States, while Duchenne is found in approximately 15.5 to 19.5 of every 100,000 live births (and not all boys with Duchenne have mutations that make them candidates for eteplirsen).
On the other hand, the estimated incidence of SMA is between one in 6,000 to one in 10,000 live births. So while helping patients and their families manage the cost of cerliponase alfa and eteplirsen 1 will be a definite challenge for neurologists who treat these patients, far more neurologists are now facing the hurdles associated with getting their patients access to nusinersen.
“Here in Utah alone, we are caring for 130 patients with SMA,” said Nicholas E. Johnson, MD, assistant professor of neurology, pediatrics, and pathology at the University of Utah, who specializes in inherited neuromuscular disorders. “If every one of those individuals is prescribed nusinersen, it would cost nearly $50 million just for the first year of treatment. That's not a sustainable approach.”
The challenge for many neurologists in prescribing nusinersen — as well as future costly drugs for other neurologic disorders, now in the pipeline — is determining which patients stand to benefit most from the drug, and which ones might be incurring six figures in drug costs annually for negligible benefit.
“There is not much data currently available to guide us as to which patients will have the most benefit with nusinersen,” Dr. Johnson said. “The phase 3 trials clearly show a survival benefit in babies with type 1, and there's a suggestion in work that the manufacturers have presented in the past that the earlier you give this therapy, the more likely the patient is to have a sustained benefit from it. But with that said, nusinersen was approved across all ages and all types of SMA, and we have minimal data about what the benefit of that therapy would be for adults with SMA, who have a much slower disease progression course than babies born with type 1.”
Imagine, he suggested, a patient in his 40s who has had only isolated thigh weakness for about five years. “He can still do pretty much everything he wants to do, but he's a little weak in some things, particularly ambulation,” Dr. Johnson said. “Will he be able to maintain that status for the next year or two without any treatment? And is adding a million dollars' worth of drug over the next two years really going to help him? It's almost impossible to make decisions like that about these very high-priced drugs.”
WORKING WITH INSURERS
To date, Dr. Johnson said, among private insurers who have published their coverage policies, 100 percent are more restrictive than the FDA's labeling. “It appears that they have been basing their coverage policies off the published clinical trial data: There is good coverage for babies with type 1 SMA. Nationwide, coverage is quite variable for children with either type 2 or type 3 SMA, although here in Utah, our primary local insurer, Select Health, has been good about working on an appropriate coverage policy, and we haven't had a substantial amount of trouble getting children with types 2 or 3 SMA covered. But we've heard that coverage is pretty poor in general for adults, and we haven't been able to get adults covered.”
Departments of neurology and individual neurologic practices do not have the ability to assist patients with paying for these drugs on a broad scale, said Bruce H. Cohen, MD, FAAN, director of the NeuroDevelopmental Science Center at Akron Children's Hospital in Ohio. “The costs of these drugs so far outstrip our ability to even begin to help patients. We don't have the tools for this. There's not a hospital in the country that I know of that's willing to underwrite their patients' drug costs. We can occasionally underwrite the medical costs of the services that we deliver to patients — such as office visits and imaging — after going through every mechanism to make sure they can't afford to pay. But we can't pay for medications that cost hundreds of thousands of dollars per year.”
Pharmaceutical companies such as Biogen, which manufactures nusinersen, do have financial assistance programs for patients who cannot afford the cost of their drugs. According to the company's public materials, the SMA360 program covers all individuals on non-government insurance, regardless of income, with no annual maximum on the amount covered. and there is no annual maximum on the amount Biogen will cover as part of the program. The program first bills the patient's insurance, and then covers the cost of any copays above the insurance payment. There are also often “free drug” programs for patients with no insurance at all.
But free drug and copay programs are restricted by federal regulation; patients who are on certain public insurance programs — particularly Medicaid — may not receive these benefits.
“The pharmaceutical companies can't provide the drug free of charge, but the patient can't afford the list price of the therapy and Medicaid can't absorb it all,” said Dr. Johnson. “The program is running on a very tight budget to begin with, and no one knows what its political future is.”
Accredo specialty pharmacy is the sole pharmacy nationwide contracted with Biogen to distribute nusinersen, and Dr. Johnson said that costs are being reduced through state Medicaid programs' contracts with the pharmacy.
Dr. Johnson said he has heard anecdotally from colleagues in other states that Medicaid programs are reimbursing substantially less per year than the list price of the drug, and there are disparities in how the states are reimbursing for the drug.
A TEMPORARY SOLUTION FOR MEDICAID
Dr. Cohen said that his hospital has worked out a temporary solution for Medicaid patients on nusinersen, at least through the remainder of 2017. “It's a complicated plan, but we are going to essentially bill Medicaid for our costs for administering the drug, and they will pay a portion. We plan to lose about $100,000-$150,000 per patient per year. But that will probably not continue into next year; we'll figure out 2018 when it gets here.”
He believes that the costs of these breakthrough drugs for previously untreatable diseases are not necessarily outrageous, despite the sticker shock. “When you look at the cost to develop them, there are probably very few people getting rich from these drugs. If you have an orphan disease and only a few thousand patients are eligible, you do the math—the end profit is not going to be that high, especially given that most of these drugs fail in development.”
Far more unreasonable, he said, is the rising costs of previously-cheap existing drugs, a phenomenon that has coincided with the growth of high-deductible health plans. As an example, he cites huge inflation in the price of the type 2 diabetes medication metformin. “It used to be pennies a dose, and now a three months' supply of metformin is $2,000 or more,” Dr. Cohen said.
But whether the price tags of nusinersen, cerliponase alfa, eteplirsen, and other as-yet-unapproved neurologic therapies are appropriate or not, neurologists still have to figure out how to help their patients afford them. At the University of Utah, a Neurology Therapy Board, consisting of neurologists and ethicists, has been established to help prescribing providers understand the risks, benefits, and utility of treatment in each particular case.
Although it was put in place immediately after the approvals of nusinersen and eteplirsen, the board could assist in decisions about other new neurology drugs as well. “It's been helpful already,” Dr. Johnson said. “It provides institutional support to help convince the insurance companies for those patients that do merit therapy, and it helps the prescribing provider work through cases when they are stuck trying to decide who is going to get the most benefit from a particular treatment.”
AAN TASK FORCE ON DRUG PRICING
Nationally, guidance will be coming from a new AAN work group, the Neurology Drug Pricing Task Force, that Dr. Johnson is chairing. Its near-term goals are to provide Academy resources for neurologists who are working through insurance approvals on costly drugs. Dr. Johnson said the group hopes to have a first set of deliverables by October.
“These are the first rationally-based disease-modifying therapies for these diseases, and instead of it being an exciting time, we have a huge burden on providers as they try to work through all the paperwork so their patients can actually get treatment,” he said. “We plan to provide best practices and coverage policies, not just for these recently-approved drugs, but for others as they come out of the pipeline.”
Anticipating that the pace of discovery will continue to pick up, the task force also aims to “find ways to bend the price curve while still encouraging research and innovation,” Dr. Johnson said. “It's unsustainable to society, and to neurology practice, to have this many really high-priced drugs.”
Dr. Cohen agrees. “We are at a remarkable time now as we are looking at treatments and cures for these terrible diseases, and it is time for a national discussion on how to pay for these treatments and sustain the industry that has delivered these miracle drugs to the pharmacopeia.”