Updated: Jan 31
On November 12th, 2021 Health Canada announced that it would grant market approval for Sanofi’s new treatment for Pompe disease, avalglucosidase alfa (Nexviazyme) (Health Canada, 2021). This treatment is a form of enzyme replacement therapy, which is now indicated in Canada for the long-term treatment of patients with late-onset Pompe disease (Health Canada, 2021b). This treatment has been approved, based on the submitted data, for all children over the age of six years and will be licensed for anyone under the age of 65 (Health Canada, 2021). Patients treated with Nexviazyme receive intravenous infusions every two weeks (Sanofi, 2021).
Pompe disease is a spectrum of rare hereditary diseases that can vary in age of onset and disease severity (National Organization for Rare Disorders, 2020). This condition is caused by gene mutations in the GAA gene which prevents the body from degrading glycogen into glucose, which is the body’s main source of energy (National Organization for Rare Disorders 2020). This results in the accumulation of this protein in skeletal and cardiac muscle, which damages tissue and impairs organ function (National Organization for Rare Disorders, 2020). The most severely affected infants often present with significant symptoms within the first three months of life (National Organization for Rare Disorders, 2020). Common clinical presentations include cardiac problems, particularly dysfunction due to heart enlargement, and generalized skeletal muscle weakness (National Organization for Rare Disorders, 2020). Patients with early Pompe disease often have a life expectancy of two years if untreated (National Organization for Rare Disorders, 2020). In late-onset Pompe disease, patients usually present with walking disabilities and reduced respiratory function (National Organization for Rare Disorders, 2020).
While avalglucosidase alfa (Nexviazyme) is not a cure for late-onset Pompe disease, it can help patients manage their symptoms. This treatment focuses on the pathway of GAA enzyme transport, which allows for increased enzyme uptake and glycogen clearance (National Organization for Rare Disorders, 2020). The use of avalglucosidase alfa (Nexviazyme) for the treatment of late-onset Pompe disease was first approved by the U.S. Food and Drug Administration this August (Sanofi, 2021), and has received Orphan Drug designation (Food and Drug Administration, 2021). Since then, Canadian patients have been waiting to receive access to this ground-breaking therapy as well (Wexler, 2021). Therefore, the granted approval in Canada in November was received with much excitement. Brad Crittenden, the executive director of the Canadian Association of Pompe, stated: “This approval is incredible news for patients and their families who are living with this debilitating disease and have limited options'' (Wexler, 2021).
Sanofi announced in August that “as part of [their] commitment to ensuring treatment access and affordability for innovative therapies, Sanofi has decided to price Nexviazyme [i.e. avalglucosidase alfa] the same as alglucosidase alfa'' (Sanofi, 2021).
For those who have been following our project, one of our case studies focuses on Fabry disease which is now being treated by another form of enzyme replacement therapy produced by Sanofi. Both Fabry disease and Pompe disease are lysosomal disorders which are conditions defined by compromised enzyme function which leads to multiple organ damage (Lukas et al., 2014).
When enzyme replacement therapies for Fabry disease were first approved by Health Canada in 2004, they received a negative funding coverage recommendation by the Canadian Agency for Drugs and Technologies in Health (CADTH) (Canadian Agency for Drugs and Technologies in Health, 2004). CADTH recommended against the coverage of enzyme replacement therapy for patients with Fabry disease, agalsidase alfa, and agalsidase beta, stating that there was insufficient evidence and that the clinical trials were of low quality (Canadian Agency for Drugs and Technologies in Health, 2004). As such, Fabry patients were left without access to this life-changing treatment and had to advocate, demonstrate, and join together with politicians and clinicians to fight for coverage of enzyme replacement therapies. This, in turn, resulted in the creation of the Canadian Fabry Disease Initiative (CFDI). The CFDI provided an alternative access pathway, allowing for the treatment of over 400 patients with enzyme replacement therapies for ten years. However, the creation of the CFDI was a lengthy and difficult process that has not yet been replicated in Canada.
Therefore, Health Canada’s approval of avalglucosidase alfa (Nexviazyme) for the treatment of late-onset Pompe’s disease is an important first step, but patients have been left to wonder if CADTH would recommend the funding for this treatment.
CADTH is currently reviewing avalglucosidase alfa. The call for patient and clinician input on this treatment opened in September 2021 and closed on October 25, 2021 (Canadian Agency for Drugs and Technologies in Health, 2021). CADTH’s review report is expected to be provided back to Sanofi in January 2022 with a draft recommendation issued in March 2022 (Canadian Agency for Drugs and Technologies in Health, 2021).
Consequently, patients have been left waiting and wondering if funding will be provided for Nexviazyme by provinces and territories for patients with late-onset Pompe disease. And if not, what kind of alternative pathway may need to be developed to ensure that patients get access to these life-saving treatments.
Our project seeks to explore the existence -and feasibility of- the kinds of alternative pathways to coverage that might be needed for access to treatments like avalglucosidase alfa (Nexviazyme) that could face negative coverage recommendations from Canadian health technology assessment authorities. It is important to note that these recommendations are just that -recommendations- and that final coverage decisions rest with each provincial drugs plan. Our study into the CFDI is revealing that these kinds of alternatives face considerable legal, political, and economic constraints, and ultimately we will be producing policy recommendations that will help to support these kinds of alternative pathways to coverage, which we consider to be social pharmaceutical innovations.
Canadian Agency for Drug and Technologies in Health. (2021, October 27). Avalglucosidase Alfa. CADTH. Retrieved November 26, 2021, from http://cadth.ca/avalglucosidase-alfa
Canadian Agency for Drugs and Technologies in Health. (2004, February 24). Agalsidase Beta. CADTH. Retrieved November 26, 2021, from https://www.cadth.ca/agalsidase-beta
Food and Drugs Administration (August 6, 2021) FDA Approves New Treatment for Pompe Disease. Retrieved January 27, 2022, from https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pompe-disease#:~:text=Nexviazyme%20also%20received%20an%20orphan,of%20Nexviazyme%20to%20Genzyme%20Corporation
Health Canada. (2021, November 12). Product information: Nexviazyme. Drug Products Database. Retrieved November 26, 2021, from https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=101150
Health Canada. (2021, November 12). Product monograph (including patient medication information): Nexviazyme. Health Canada. Retrieved November 26, 2021, from https://pdf.hres.ca/dpd_pm/00063565.PDF
Lukas, J., Pockrandt, A. M., Seemann, S., Sharif, M., Runge, F., Pohlers, S., Zheng, C., Glaser, A., Beller, M., Rolfs, A., & Giese, A. K. (2014). Enzyme enhancers for the treatment of Fabry and Pompe disease. Molecular Therapy, 23(3), 456-464. 10.1038/mt.2014.224
National Organization for Rare Disorders. (2020, January 12). Pompe Disease - NORD. National Organization for Rare Disorders. Retrieved November 26, 2021, from https://rarediseases.org/rare-diseases/pompe-disease/
Sanofi. (2021, August 6). FDA approves Nexviazyme® (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease. Sanofi. Retrieved November 26, 2021, from https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-06-17-42-21-2276588
Wexler, M. (2021, November 16). Nexviazyme for Late-onset Pompe Approved in Canada as Next-gen ERT. Pompe Disease News. Retrieved November 26, 2021, from https://pompediseasenews.com/2021/11/16/nexviazyme-late-onset-pompe-approved-canada-next-gen-ert/
Written by: Shir Grunebaum (MA) and Conor Douglas (PhD)
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