Implementing a Global Expanded Access Program (EAP) for Infantile-Onset Spinal Muscular Atrophy (Type I): Understanding the Imperative, Impact and Challenges

Abstract

Nusinersen is the first disease-modifying therapy approved for the treatment of spinal muscular atrophy (SMA), a rare genetic disorder characterized by severe progressive muscular atrophy and weakness. An expanded access program (EAP) provides investigational treatment to patients without other treatment options. An EAP providing nusinersen treatment to individuals with the most severe form of SMA, infantile-onset SMA (consistent with SMA Type I), has enrolled over 800 participants as of September 2018, making it one of the largest in rare disease history. The successes, challenges experienced and opportunities for future consideration during the implementation of the nusinersen EAP are discussed.

Keywords: Compassionate use; antisense oligonucleotides; antisense oligodeoxyribonucleotides; drug therapy; expanded access trial; neuromuscular disease; orphan drug; rare disease; spinal muscular atrophy.

Fig. 1

Nusinersen expanded access program (EAP) enrollment. The nusinersen EAP has become one of the largest in rare disease history, enrolling 835 individuals with spinal muscular atrophy (SMA) in 120 centers across 30 countries as of September 20, 2018. Countries utilizing a Named Patient EAP mechanism included Australia, Austria, Canada, Colombia, Czech Republic, Denmark, Finland, Greece, Hong Kong, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Slovenia, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey, and the United Kingdom. Countries utilizing a Group/Cohort EAP mechanism included Belgium, France, Germany, and the United States. Of note, France initiated EAP participation using a Named Patient program (Nominative temporary authorization for use [ATU]) and later transitioned to a Group/Cohort program (Cohort ATU).

Fig. 2

Age of symptom onset and the survival motor neuron 2 (SMN2) copy number in participants enrolled in the nusinersen expanded access program. ^aOut of the 776 participants with age of onset of symptoms ranging from 0 to 6 months. ^bOut of the 381 participants who reported SMN2 copy number.