Below is an outline of the regulatory appraisal process of Spinraza in England and Wales.

Background

In March 2018, the National Institute of Health and Care Excellence (NICE) finally started the process of appraising the only treatment licenced in the European Union for spinal muscular atrophy (SMA). Spinraza (nusinersen) has shown a significant benefit for the majority of patients with SMA in clinical trials, including an increase in survival rate and higher scores in motor function development. Unfortunately, due to the nature of SMA, the clinical trials reflected only a small number of the SMA population and for the rest the data had to be extrapolated. Combining this apparent lack of data, population numbers and cost of the drug resulted in a delay in making a decision as to which appraisal route NICE should take.

NICE has established two relevant regulatory routes for appraising new medicines: the Single Technology Appraisal (STA) and the Highly Specialised Technologies evaluation (HST) route.

Broadly speaking, the STA route has been designed to assess treatments for use in broad populations. Apart from the standard clinical efficacy analysis, treatments appraised under STA have to pass a rigorous value-for-money test. NICE’s recommendations for STA stipulate that a treatment that brings a patient from severe disability and certain death to full health should cost no more than £30,000 per patient per year. Treatments that bring about less improvement must cost proportionately less.

The other route, HST, was introduced recently for highly specialised life-saving interventions that are carried out in a handful of patients only (usually, no more than 100 patients per year); mostly in ultra-rare indications. This route allows for a significantly higher treatment per-patient cost.

Nusinersen can be considered a highly specialised technology, because SMA is an ultra-rare disease and nusinersen therapy does save lives. Therefore, initial discussions with NICE centred on the HST route.

However, based on academic publications on the natural history of SMA, nusinersen can be termed as “life-saving” only with regard to SMA type 1 where mean life expectancy is around 11 months. Therefore, if it was appraised under HST, those with milder SMA types (2, 3 and 4) would necessarily be excluded.

Our work

TreatSMA has sought to convince NICE that any such exclusion from treatment is not supported by science or clinical evidence and would be unacceptable to the UK SMA community. We reiterated that nusinersen proved clinically effective and was approved by the European Medicines Agency across the entire spectrum of spinal muscular atrophy. It therefore must be made available to all people with SMA regardless of type/severity, symptoms, functional status, age, postcode, or any other arbitrary criteria.

We acknowledged that the manufacturer’s revenue expectations might pose a challenge when measuring the budget impact if treatment is to be offered to everyone, especially as the milder forms of SMA might not fit in the cost-benefit guidelines. However, we decided to rely on the manufacturer’s oft-stated commitment to make this treatment available to everyone with SMA and expect that the company will take the UK regulatory framework and NHS budget realities into account.

As discussions progressed, it became apparent that certain elements from the HST evaluation can be “borrowed” to assess Spinraza under general STA guidelines.

Ultimately, our efforts bore fruit and NICE agreed to appraise nusinersen as a treatment for everyone with SMA.

Current situation

As the appraisal procedures commenced, the UK SMA organisations started to compile evidence about the impact of SMA and the need for treatment. TreatSMA reached out to SMA families who have been treated with nusinersen under the Expanded Access Programme and asked them to describe the treatment effects. We also reached out to those who waited for treatment and gathered evidence on the impact of SMA on many aspects of daily life. Our aim was to collect Real World Evidence (RWE) of Spinraza effects as compared to no treatment.

Real World Evidence is crucial in making decisions on how the given treatment should be offered. It better reflects the way treatment works in real life compared to data from a manufacturer-sponsored clinical trial. So, Real World Evidence for nusinersen supported an introduction of treatment to those with other types of SMA in addition to SMA type 1.

In our formal submission to NICE – which was prepared by a fantastic team of dedicated TreatSMA families – we provided a raw account of what life with SMA really is and what we people affected by SMA understand as a meaningful treatment outcome. We showed the deterioration before, and gains after, Spinraza treatment. Instead of percentages and numbers we decided to provide raw accounts.

What next

The appraisal process will take a few more months. A NICE committee will meet to review the nusinersen file on 27 June. After the Committee adopts their opinion and all the stakeholders will have had an opportunity to comment on it, a final NICE recommendation will be published on 21 November 2018.

We are aware that a wide therapeutic indication combined with absurdly high price tag may make Spinraza fail the value-for-money test and a budget impact test and that it is quite possible that NICE may not be able to recommend Spinraza for everybody with SMA.

So, work is now ongoing on setting up some form of Managed Access Scheme in which NHS purchases the drug and offers it to patients individually assessed as eligible. Normally it takes approximately 18 months to put a Managed Access Scheme in place, and negotiations start only after NICE appraisal is finalised. In the case of nusinersen, NICE agreed that negotiations on Managed Access can start right away in order to reduce the delay to treatment.

TreatSMA will continue to represent the SMA Community during all the proceedings.

Acknowledgement

We would like to thank all of the SMA Families who participated in our data collection efforts through providing their testimonies and stories. We know how difficult it is to find time and words to describe life with SMA.

We also thank SMA Support UK for sharing our request for family testimonials in their monthly newsletter: we as a community need to stand together as one.