Devastating. Heartbreaking. A death sentence for an estimated 1,000 children with spinal muscular atrophy (SMA).
These are among the many angry reactions to Tuesday’s appraisal consultation document issued by a committee of Britain’s independent, government-funded National Institute of Health and Care Excellence (NICE). That opinion recommends against Spinraza (nusinersen), an approved SMA treatment, being added to the subsidized public health system of England and Wales because of its “extremely high cost.”
Northern Ireland is expected to follow the agency’s guidance.
The NICE committee concluded that, based on its list price, the treatment’s annual cost-effectiveness ranged between £400,000 and £600,000 ($508,000 to $763,000) per Quality Adjusted Life Year (QALY) gained, and that “even with a proposed confidential price reduction, the cost of nusinersen is too high for it to be considered a cost-effective use of NHS [National Health Service] resources.”
While conceding that Spinraza “provided a substantial clinical benefit,” the committee “felt that there were a lot of uncertainties” around the long-term benefits of the medicine, which is injected directly into the spine.
“We are actively engaged with Biogen to discuss how they might address the uncertainties identified by the committee, while demonstrating the potential for nusinersen to be considered cost-effective and managing the risk to the NHS of allowing access to the treatment,” said Meindert Boysen, director of the Centre for Health Technology Evaluation at NICE, in an Aug. 14 press release.
The draft guidance is open for public consultation until Sept. 5. Comments can be submitted to NICE via this link. A second appraisal committee meeting is set for Oct. 23, possibly in advance of NICE’s original decision date of Nov. 21.
If NICE’s final opinion is against Spinraza — meaning the treatment will not be available for low or no cost through the NHS — fewer than 100 children with SMA type 1 in those three countries will be able to continue accessing it. And this use comes only through the Expanded Access Program set up by its manufacturer, Biogen, in 2016, with no guarantees the program will continue.
In Scotland, a part of the U.K. but with its own NHS system, Spinraza has been available for SMA type 1 patients since May. The Scottish Medicines Consortium also may consider wider use under its recently established “ultra-orphan treatment” category.
Muscular Dystrophy UK, which is coordinating its response to the NICE opinion with two other nonprofit groups, SMA Support UK and The SMA Trust, previously warned that “Spinraza is one of many effective treatments for rare diseases that will struggle to win approval” unless more flexible processes are adapted.
“Spinal muscular atrophy can be devastating, and today’s news is heartbreaking for the families of those living with the condition,” MDUK’s chief executive, Robert Meadowcroft, said in a statement on the charity’s website. “Once again, we are seeing families suffer due to the appraisal process being too limited to assess costly but life-changing rare disease drugs.”
NICE rejection a bargaining tactic?
Mencia de Lemus Belmonte is president of SMA Europe, an umbrella organization made up of 18 national associations representing 16 countries. A native of Spain, she also heads the Fundación Atrofia Muscular Espinal España and has two children with SMA type 2.
“I’m devastated by this news,” Belmonte said in a phone interview from Madrid. “Although negotiations didn’t look good from the outside, we never expected such an outcome. We believe patients must come first. There’s a very high unmet need for SMA, and now one drug is available that changes the natural history of the disease. From the patient’s perspective, price should not drive a decision that has such an impact on peoples’ lives.”
Belmonte said the NICE decision could have repercussions for other countries in the 28-member European Union, home to anywhere from 15,000 to 25,000 people with SMA. About one in 11,000 babies is born with SMA, the most common genetic cause of infant death.
Spinraza, one of the world’s most expensive medicines, was approved across the EU for all SMA types (chromosome 5q SMA) in June 2017. The therapy earned the blessing of the U.S. Food and Drug Administration (FDA) in December 2016.
“Getting Spinraza covered was difficult in some countries, but no one has been as harsh as NICE,” Belmonte told SMA News Today.“It’s so hard for me to believe that a national agency of a European country that has a sound economy would reject such an important drug for such a devastating disease for economic reasons.”
Italy offers Spinraza for all types of SMA, while EU member states such as Greece and Portugal, both of which have much lower per-capita incomes than Britain, completely subsidize Spinraza for type 1 patients.
“I think they’re trying to negotiate the price. That’s why they announced an initial rejection,” said a European rare disease patient advocate who is not being named because of how this speculation might be interpreted. “This is not the first time this has happened with NICE. … It’s very disappointing, but it’s a negotiating tactic.”
NICE also may “want to stall” on SMA treatment, the advocate added, because of gene therapies for SMA that are working their way through clinical trials.
Biogen said it was “deeply disappointed but not surprised” by the decision. In an Aug. 15 statement to the SMA community at large, it criticized the Single Technology Appraisal process as “unsuitable to assess a rare disease medicine such as nusinersen” that would benefit few people. That, the Massachusetts-based company added, is why it has been working with NICE and NHS England from an early stage to discuss a managed access agreement (MAA) to make Spinraza available while continuing to gather information about how it works.
“Biogen recognizes that this decision marks a concerning day for SMA patients and their families, and we share that concern. England, Wales and Northern Ireland are now significantly behind in making nusinersen available, with 20 European countries … granting access,” it said. “However, Biogen remains optimistic that a MAA can be achieved if all relevant stakeholders continue to meaningfully engage to find a solution.”
SMA advocate: Britain behind the times
Kacper Rucinski is a London-based executive member of SMA Europe, who’s been advocating for better U.K. access to Spinraza for several years through his involvement with Treat SMA.
“It was because we pushed so hard that we managed to have expanded access in the U.K.,” he said. That program benefits about 70 people in England “and a handful more in Scotland,” though some 1,000 patients are still waiting for the therapy.
Rucinski, whose daughter has SMA type 2, called the NICE recommendation “the consequence of a very outdated process of appraising breakthrough drugs for rare diseases where the population of patients who would benefit is very small.”
He noted that under such guidelines, NICE cannot recommend a treatment if the cost of one quality-adjusted life-year (QALY) gained through its use exceeds £30,000 (about $38,140).
“The second problem is that NICE has not used all the available evidence,” he said. “They focused almost exclusively on randomized control trials — which in SMA were conducted in 300 to 400 people years ago — and did not take into consideration whatever information was gained in later expanded access programs.”
But, Rucinski added, “this negative decision does not prohibit the NHS from negotiating an agreement, so there are big hopes that it will engage in negotiations and buy the drug from Biogen for a wider population.”
NICE is expected to issue its final recommendation on Nov. 21, but Rucinski believes a December or January announcement more likely.
“If the final recommendation is a no, then there won’t be any treatment of SMA in England, Wales and Northern Ireland. One thousand people will have no access to Spinraza,” Rucinski said.
Rucinski, who also is president of SMA Foundation Poland, had harsh words for Britain’s healthcare system in general, which he claims puts rare disease patients at a disadvantage.
“The government bureaucracy here is focused on avoiding responsibility,” he said. “There’s very weak or non-existent healthcare policy and no leadership role here, leaving this country unable to catch up with the 21st century.”