SPINRAZA, a common point of discussion in the rare disease space is a synthetic anti-sense oligonucleotide, a type of genetic material, that can be used to treat children and adults with spinal muscular atrophy (SMA) (European Medicines Agency, 2017). SMA is a rare disease which affects approximately 1 in every 10,000 people, affecting both males and females (National Organisation for Rare Disorders, 2022). This group of rare conditions is characterised by the loss of nerve cells in the spinal cord (lower motor neurons) (National Organisation for Rare Disorders, 2022). People affected by this condition often experience significant muscle weakness and atrophy, hypotonia, decreased or absent reflexes, and twitching muscle fibres.
SPINRAZA is one of the most expensive drugs for rare diseases and has caused a significant amount of controversy all around the world as a result of its significant price. In Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH) approved SPINRAZA in 2017 under three conditions (CADTH, 2017). The first condition was that Biogen Canada Inc, the producers of this medication, offer a substantial reduction in price (CADTH, 2017). The second condition was that SPINRAZA could only be provided under the care of a specialist with experience in the diagnosis and management of SMA (CADTH, 2017). Furthermore, CADTH advised that the collection of real-world evidence would need to be provided in the use of nusinersen for the treatment of SMA (CADTH, 2017). For those who are involved in the rare disease world, or those who have read our previous blog posts, this is a notable type of alternative coverage pathway, which is fairly rare in Canada.
Nevertheless, patients with 5q spinal muscular atrophy gained access to this expensive but life saving treatment about 5 years ago. Importantly, this was only a subset of the SMA population and this medication was only offered to patients with SMA that had a deletion of the SMN1 gene (CADTH, 2017; National Organisation for Rare Disorders, 2022). While 92% of all patients with SMA have this type of condition (Slayter et al., 2021), there are actually 5 different types of SMA (National Organisation for Rare Disorders, 2022). In 2019, after another CADTH review process, access for the treatment of 5q SMA across all types of patients, including patients of all ages and those that were presymptomatic was granted as well (CADTH, 2019).
In May of this year, Biogen Canada Inc. applied for the approval of the use and reimbursement of SPINRAZA for patients with type II and III SMA. Patients with type II can often sit independently early in their development but lose this ability in their mid-teens (National Organisation for Rare Disorders, 2022). Individuals with type II SMA can never achieve independence in walking or standing and often have difficulty swallowing and breathing, experience significant tremors, and have scoliosis (National Organisation for Rare Disorders, 2022). In contrast, patients with III SMA often experience significant hip and leg weakness and are at a high risk of falls (National Organisation for Rare Disorders, 2022). Nevertheless, they are often able to walk and stand independently but this is usually lost with disease progression National Organisation for Rare Disorders, 2022).
Earlier this week, SPINRAZA was granted a negative reimbursement for patients with type II and III SMA who are older than 18 years of age regardless of ambulatory status (CADTH, 2022). This negative reimbursement recommendation was provided as CADTH indicated that the available clinical studies were not comparative in nature and as such could not provide conclusive evidence to prove the benefit of this treatment in the stated population (CADTH, 2022). Further, the model based on motor function milestones which was provided by Biogen Canada Inc in preparation for the review did not capture all key aspects of SMA in adult patients (CADTH, 2022). In addition, CADTH stated that the submitted model had technical limitations and the results produced a lack of validity (CADTH, 2022). While members of the scientific community recognise the importance of high-quality evidence-based decisions such as these, many in the rare disease community are still devastated that a treatment will not be available for patients with type II and III SMA.
In moments like this, it may be helpful for pharmaceutical companies and governments to consider the role of alternative access pathways, such as alternative financing schemes (ex: pay-for-performance). Alternatively, in similar situations in the past, some pharmaceutical companies have provided treatment for free to patients as they gather evidence for a new treatment group. Through research on Social Pharmaceutical Innovation (SPIN), we hope to better understand how these types of agreements are being applied around the world and how we might be able to learn more previous experiences.
References
CADTH. (2017, December 20). CADTH Canadian Drug Expert Committee Recommendation: Nusinersen (Spinraza - Biogen Canada Inc.). CADTH Canadian Drug Expert Committee Recommendation. Retrieved September 2, 2022, from http://cadth.ca/sites/default/files/cdr/complete/SR0525_Spinraza_complete_Dec_22_17.pdf
CADTH. (2019, February 27). CADTH Canadian Drug Expert Committee Recommendation: Spinraza - Biogen Canada Inc. CADTH Canadian Drug Expert Committee Recommendation. Retrieved September 2, 2022, from https://www.cadth.ca/sites/default/files/cdr/complete/SR0576-Spinraza-Resubmission-Mar-1-19.pdf
CADTH. (2022). CADTH Reimbursement Recommendation: Nusinersen (Spinraza). Canadian Journal of Health Technologies, 2(8), 1-18.
European Medicines Agency. (2017). Spinraza. European Medicines Agency. Retrieved September 2, 2022, from https://www.ema.europa.eu/en/medicines/human/EPAR/spinraza
National Organisation for Rare Disorders. (2022). Spinal Muscular Atrophy. National Organisation for Rare Disorders. Retrieved September 2, 2022, from https://rarediseases.org/rare-diseases/spinal-muscular-atrophy/
Slayter, J., Hodgkinson, V., Lounsberry, J., Brais, B., Chapman, K., Genge, A., Izenberg, A., Johnston, W., Lochmüller, H., O'Ferrall, E., Pfeffer, G., Plamondon, S., Rodrigue, X., Schellenberg, K., Shoesmith, C., Stable, C., Taillon, M., Warman-Chardon, J., Korngut, L., & O'Connell, C. (2021). A Canadian spinal muscular atrophy outcome measures toolkit: Results of a national census using a modified delphi method. Journal of Neuromuscular Diseases, 8(4), 579-588. 10.3233/JND-200617
Photo credit: National Cancer Institute (2020). Person wearing scrubs holding hand [Image]. https://unsplash.com/photos/BxXgTQEw1M4
Written by: Shir Grunebaum (MSc)