Position Statement: Emerging genetic therapies for rare disorders at high cost, cannot realistically address the global burden of disease

Emerging genetic therapies for rare disorders at high cost, cannot realistically address the global burden of disease - Stakeholders must develop new pathways to ensure safe, fair and sustainable provision of such therapies

A disease or disorder is defined as rare in Europe when it affects fewer than 1 in 2000 people and based on the Food and drug administration (FDA) definition from the US, when it affects less than 200,000 at any one time. Genetic factors contribute to the etiology in 80% of those with rare diseases, and other contributing factors, including infection, account for the remaining the cases. The recent emergence of gene technologies has led to the development of therapies to treat some of the once incurable diseases. Currently, there are more than 230 gene therapy efforts such as splicing modifiers, exon skipping protocols, monoclonal antibodies, and several ‘molecular plaster’ studies. Increasing numbers of these therapies are being demonstrated to show benefit and are being approved by health care authorities leading to availability in the market [1-4].

However, although these discoveries have provided the real possibility of treatment and cure to previously considered untreatable and often life-limiting diseases, at this point several concerns have arisen including primarily the high cost, access to the intervention and the potential risks [5]. These are mainly based on the following independent factors. First, clinical studies are conducted on a narrowly defined group with a minimal number of cases (usually less than 200), but the therapy is expected to be applied to a more diverse population. For example, a molecule has been approved by the FDA in all types of a given rare genetic disorder, however the original study was only conducted in babies less than 6 months of age [1,6]. Secondly at this time the adverse effects portfolio in relation to these treatments is still accumulating, adequate data may not be available on chronic and late stage forms of disease, and uncertainities exist regarding long term benefits [2-4]. The third issue is related to cost regulation. These drugs are extremely expensive costing up to several million dollars which places governmental bodies and health care providers in a difficult position financially based upon the cumulative cost of several hundred re-imbursements every year causing a true burden on the health economy globally [5, 7]. Last but not least is the issue of the expectations of families which may not match with the study end points. In other words, ‘End point goals’ of patients and families in terms of clinically relevant outcomes and improvements in quality of life may differ significantly from those included in study protocols [8].

Since the 1980s there have been enormous developments in the whole gene therapy field which has led to significant expectations in the community. For the time being, these innovative therapies act as disease modifying procedures at often prohibitive costs. But even if they fall short of mitigating all functional limitations in patients or eliminating morbidities and not fulfilling in total the families’ expectations, those involved in the care of affected children continue to think positively. More effective treatments may be here sooner than expected, although we are still years away from definitive treatments. The cost of these interventions will become an increasing obstacle not only for resource poor settings but also for resource-rich regions if the current trend is maintanied. Going forward there needs to be careful consideration of the cost benefit ratio of these interventions given the limited amount of resources available to provide healthcare to the entire population.

The position statement of the ICNA proposes that counterparts, regulators, decision makers and other party stakeholders should work in unity to address this serious global health matter for vulnerable children and families. Characterizing these perspectives can help support decisions. High cost is a potential barrier to accessing treatment worldwide negating the possibility for impact for the majority of those afflicted.

The Position Statement was compiled by Professor Haluk Topaloğlu and reviewed, adapted and endorsed by the ICNA Advocacy committee (Pauline Samia (chair), Adam Kirton, Russell Dale, Chahnez Charfi Triki, Anaita Hedge, Helen Cross, Edward Kija, Silvia Tenembaum, Richard Idro and ICNA officers Jo Wilmshurst and Ingrid Tein.

References:

1. Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. New Engl J Med 2017; 377:1723-1732. doi: 10.1056/NEJMoa1702752.
2. Michelson D, Ciafaloni E, Ashwal S, Lewis E, Narayanaswami P, Oskoui M, Armstrong MJ. Evidence in focus:Nusinersen use in spinal muscular atrophy. Report of the guideline development, dissemination, and implementation subcommittee of the American Academiy of Neurology. Neurology 2018;91: 923-933. doi: 10.1212/WNL.0000000000006502
3. Unger EF, Califf RM. Regarding ‘’ Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 2017; 81: 162-164 doi: 10.1002/ana.24842
4. Groen EJN, Talbot K, Gillingwater TH. Advances in therpay for spinal muscular atrophy:promises and challenges. Nat Rev Neurol 2018;14:214-224. doi: 10.1038/nrneurol.2018.4.
5. Burgart AM, Magnus D, Tabor HK, Paquette ED, Frader J, Glover JJ, et al. Ethical challenges confronted when providing nusinersen treatment for spinal muscular atrophy. JAMA Pediatr 2018; 172: 188-192. doi: 10.1001/jamapediatrics.2017.4409.
6. Parente V, Corti S. Advances in spinal muscular atrophy therapeutics. Ther Adv Neurol Disord. 2018 Feb 5;11:1756285618754501. doi: 10.1177/1756285618754501. eCollection 2018.
7. Shawi F, Perras C, Severn M. Emerging drugs for Duchenne muscular dystrophy. CADTH issues in emerging health technologies 2017; 161: 1-19.
8. Pacione, M, Siskind CE, Day JW, Tabor HK. Perspectives on spinraza (nusinersen) treatment study: views of individuals and parents of children diagnosed with spinal muscular atrophy. J Neuromuscular Disord 2019; 6:119-131. doi: 10.3233/JND-180330.

This Open Access article was originally published in the Journal of the International Child Neurology Association (JICNA). 

Citation: Samia, P., Kirton, A., Dale, R., Tenembaum, S., Triki, C., Hegde, A., Idro, R., Kija, E., Wilmshurst, J., Tein, I., & Topaloğlu, H. (2019). Position Statement:Emerging genetic therapies for rare disorders. Journal of the International Child Neurology Association. Retrieved from https://jicna.org/index.php/journal/article/view/172

Related:

The Cost of Drugs for Rare Diseases Is Threatening the U.S. Health Care System (A. Gordon Smith, Harvard Business Review, APRIL 07, 2017)
Hesselgrave BL (2003) Helping to manage the high cost of rare diseases. Manag Care Q 11 (1):1-6. PMID: 12790059.
(2017) Treating rare disorders: time to act on unfair prices. Lancet Neurol 16 (10):761. DOI: 10.1016/S1474-4422(17)30295-8 PMID: 28920873.
High cost of undiagnosed rare diseases (ITV Report: 17 December 2018)