The “exorbitant” cost of nusinersen (Spinraza; Ionis Pharmaceuticals/ Biogen), a new drug for spinal muscular atrophy (SMA), and complicated logistics related to its administration are restricting access to treatment, experts say.
A group of bioethicists and clinicians involved in the care of patients with SMA are voicing their concerns over patient access to nusinersen, the first treatment for the life-limiting condition, which affects mainly infants and children, in a paper published online December 11 in JAMA Pediatrics.
“Nusinersen was approved in December last year, so it has been available for a year now. Some families will still be unaware of its availability, and others will live too far from a center offering it. But payment for the drug is the main issue limiting its use. We know families are experiencing barriers and delays to treatment because of reimbursement issues,” lead author, Alyssa Burgart, MD, Stanford University School of Medicine, California, told Medscape Medical News.
SMA is hereditary neuromuscular disease caused by a mutation in the SMN1 gene affecting 1 in 10,000 live births. The mutation causes abnormal expression of the SMN protein, leading to progressive muscle weakness and often eventual death.
The several different types of the disease reflect time of onset and severity of the condition (types 0 to 4), with type 0 occurring before birth and resulting in death soon after birth; type 1 starting to appear at about 6 months of age, with most infants not surviving beyond age 2; type 2 presenting in early childhood; type 3 presenting in later childhood; and type 4 presenting in adulthood.
Nusinersen is an antisense oligonucleotide therapy that increases expression of the SMN protein. The medication is administered intrathecally via repeated lumbar punctures, with four doses given during the first 2 months, then one dose every 4 months thereafter. Biogen has priced the drug at $125,000 per dose, leading to an annual cost of $750,000 in the first year and $375,000 in subsequent years.
The US Food and Drug Administration approved nusinersen at the end of 2016 for all types of SMA based on data from one randomized trial (ENDEAR) in infants with type 1 SMA — which showed significant motor function improvement with the drug — and uncontrolled data on other types.
This trial was published recently in the New England Journal of Medicine. A second randomized trial (CHERISH) has also found benefits in children with type 2 or 3 SMA, but the results have not yet been published.
Dr Burgart estimates that about 8000 to 10,000 people are living with SMA in the United States — mainly infants and children.
Number 1 Concern Is Cost
The study authors looked at the issues various hospitals had to consider when offering this treatment.
“The first and most important issue is cost. This is everyone’s number 1 concern. We are not sure how insurers are going to deal with the massive cost, and hospitals could literally go bankrupt trying to deliver this therapy to those who are not covered. And then there’s all the other healthcare costs associated with administering the therapy, including interventional radiology and anesthesiology services,” said Dr Burgart.
“In an ideal world, if a physician prescribes this medication and the family wants it then there would be unlimited access to it, but this is clearly not going to be practical in this case,” she added.
The author of an accompanying editorial, Vinay Prasad, MD, MPH, Division of Hematology Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, asks whether insurers can say no to paying for nusinersen.
“One of the tragedies is that this is a question that has to be asked. And that’s because the cost is so high,” he said in an audio interview with JAMA Pediatrics.
Dr Prasad elaborated on the issues that have to be considered. He explained that in the ENDEAR trial nusinersen was associated with an increase in “motor milestone” responders — defined as infants who showed improvement in at least one category of kicking, head control, rolling, crawling, or walking. Patients also had to have more categories with improvement than categories that worsened.
With this definition of “responder,” the nusinersen group had 40% responders vs 0% in the placebo group, and if patients on mechanical ventilation are excluded, the response rate drops to 33%, he reported.
“This seems quite impressive but because the results are dichotomized we lose some information. For example, to look at the improvement in context, the benefit with the drug was an average of 3 points (from 1 point to 4 points) on the Hammersmith Infant Neurological Examination (HINE) scale over a 6-month period.
“But a healthy child would have a score of 22 points. So we are only seeing a small effect. While there were some infants who had a greater response, there were only 4 patients (out of 52) who had a greater than 10-point improvement. So although this treatment is a step forward it is a long way from a cure,” he said.
Dr Prasad noted that “when high costs and marginal benefits combine, payors are put in a very difficult position. There is a finite pot of money. How can they balance the interests of patients with SMA with those of their patients with other conditions who also need expensive treatments?”
“This pushes the insurer to set some arbitrary conditions on payment. For example, if the patient has not improved by some number of points on the HINE scale, then coverage is stopped,” he said.
Plea to Lower the Price
Dr Prasad added that under the principle of evidence-based medicine, insurers could limit reimbursement to infants with SMA type 1 similar to those include in the ENDEAR trial. Or they may exclude patients for whom the improvement may be too little, too late.
“These are rational ways that insurers may deny coverage, and they will have been forced into this position by the price of the drug. The price the manufacturer has set is far too high — it has put everyone in a very difficult position. The easiest way to improve the value of this medication is to lower the price,” he added.
Dr Burgart agrees. “We all want more effective therapies, but as a society we have to address how we pay for them. What other services do we not provide if there is unlimited access to this one agent?”
She said she and her colleagues are hearing different information from patients about what insurers will cover.
“Some are placing milestones (in terms of clinical improvement) that have to be reached to continue coverage. This places families in a very difficult position.”
She added that some patients have also mentioned barriers to accessing the Biogen assistance program for those who aren’t covered by insurance.
“You hate for the price tag to be the reason that a family has to be devastated all over again, as if the devastation of a diagnosis isn’t enough.”
Hospitals are also having to battle with the cost of this new treatment while also considering their institutional mission.
“If you are interested in making money, you can cherry pick your patients and only take those with insurance. But how can you do this if your mission is to provide the best possible care to your patients?”
Biogen Responds
Responding to the concerns raised in the JAMA Pediatrics papers, Biogen said nusinersen “has demonstrated breakthrough clinical value in SMA…bringing families hope and patients who previously had no approved treatment options a chance for life. The ENDEAR results highlighted that most infants receiving nusinersen showed meaningful benefit in both function and survival. The study also showed that earlier start of treatment may provide greater improvement in motor function and survival outcomes.
“As a pioneer in neuroscience, Biogen is driven by unmet medical need, not the numbers of patients who need treatment. Biogen has invested nearly $900 million to bring nusinersen to market, and our investment in SMA continues with post-launch studies and other research, including advancing potentially new therapies to the SMA community.”
“Biogen remains fully committed to patient access to nusinersen and offers patient support programs that assist with insurance benefits investigation and financial assistance, as well as programs to support physicians in addressing administration challenges. In the US, 80-85% of patients have coverage. We will continue working with all parties so that people who could benefit from nusinersen may receive access to this new treatment option as quickly as possible,” the company added.
Dr Burgart has disclosed no relevant financial relationships. Dr Prasad reports receiving royalties from his book Ending Medical Reversal.
JAMA Pediatr. Published online December 11, 2017. Full text, Editorial
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